Combined intraocular and systemic rituximab for ocular lymphoproliferative disorder with extranodal marginal zone lymphoma-type morphology after heart transplant.

Post-transplant lymphoproliferative disorder (PTLD) has rarely been associated with ocular manifestations. We report a case of bilateral ocular involvement by PTLD with histopathologic features of extranodal marginal zone (MALT) lymphoma in an 8-year-old boy following orthotopic heart transplantation. The anterior segment disease was treated successfully using a combination of intraocular and systemic injections of humanized anti-CD20 antibody (rituximab).

Manifestaciones pulmonares en la neurofibromatosis tipo 1: una asociación a tener en cuenta / Pulmonary manifestation in neurofibromatosis type 1, an association to be considered

La neurofibromatosis tipo 1 es la enfermedad neurocutánea más frecuente. Es un trastorno genético con herencia autosómica dominante que produce alteraciones principalmente en la piel y en el sistema nervioso, pero también en otros órganos. La afectación pulmonar en pacientes con neurofibromatosis se ha descrito como una complicación rara que aparece principalmente en adultos. Presentamos el caso de un adolescente no fumador con neurofibromatosis tipo 1 y manifestaciones pulmonares asociadas (AU)

Neurofibromatosis type 1 is the most common neurocutaneous disease. It is a genetic disorder inherited as an autosomal-dominant trait, which leads to abnormalities mainly in the skin and in the nervous system, but also in other organs. Pulmonary involvement in patients with neurofibromatosis has been described as a rare complication, which mainly affects adults. We report the case of a non-smoker adolescent male with neurofibromatosis type 1 and associated pulmonary manifestations (AU)

New insights into oculodermal nevogenesis and proposal for a new iris nevus classification.

BACKGROUND/AIMS: To gain more knowledge about presence and dermatological associations of iris nevi as well as possible pathways involved in the formation of iris nevi. METHODS: We conducted a prospective, interdisciplinary observational study. Presence, morphology, topography of iris and cutaneous nevi as well as factors indicating sun-exposure were noted. RESULTS: A total of 632 participants including 360 (57%) women were examined. Of those, 26 subjects revealed 27 iris nevi. According to the current classification, all iris nevi were judged as solitary with the majority of them (n=20; 74%) located in the lower quadrants. In six (22.2%) cases we noted a peculiar 'incomplete sectoral pattern'; these nevi were located close to the pupil, were larger and had a more elongated, triangular shape compared with those located distant from the pupil, which appeared smaller and more roundish. Notably, five of these six peculiar (incomplete sectoral) iris nevi were located on the upper half of the iris. CONCLUSIONS: Based on our findings we propose classifying iris nevi into sectoral, incomplete sectoral and solitary subtypes. Additionally, we set up a hypothetic concept of oculodermal nevogenesis suggesting a time-dependent embryogenic alteration affecting the normal melanocyte location, migration and maturation along peripheral nerve sheets. Our new concept explains well the morphology and extension of benign melanocytic proliferations in the ocular region as well as their relation to uveal melanoma.

Iris melanoma arising from sector congenital ocular melanocytosis in a child.

PURPOSE: To report a clinicopathologic correlation of a melanoma arising from iris component of ocular melanocytosis in a child. METHODS: A 13-year-old boy developed a progressive iris nodule arising from sector iris pigmentation that was a component of congenital ocular melanocytosis involving the iris, ciliary body and choroid. The tumor was examined clinically and with ultrasound biomicroscopy (UBM), removed by peripheral iridocyclectomy, and studied histopathologically. RESULTS: Clinically, the pigmented nodule was 3 mm in diameter, located within the sector iris pigmentation, and was 2.4 mm in thickness as measured by UBM. Histopathologically, it was composed predominately of spindle B melanoma cells with adjacent spindle and dendritic melanocytes compatible with iris melanocytosis. CONCLUSION: Although highly unusual, melanoma can arise in the sector iris pigmentation that is often a component of congenital ocular melanocytosis. Even young patients with ocular melanocytosis should be examined periodically for development of melanoma in the ciliary body and choroid.

A quantitative assessment of the burden and distribution of Lisch nodules in adults with neurofibromatosis type 1.

PURPOSE: The presence of two or more Lisch nodules (melanocytic hamartomas of the iris) is one of seven diagnostic criteria for neurofibromatosis type 1 (NF1), a common monogenic disorder of dysregulated neurocutaneous growth. The hypothesis that Lisch nodules arise secondary to exposure to ultraviolet (UV) radiation from sunlight was investigated. METHODS: Lisch nodule burden was mapped and quantified in the irides of 77 adults with NF1. Lifetime sunlight (UV radiation) exposure was inventoried, NF1 neurocutaneous severity determined, and two NF1 mutations predictive of severity selectively genotyped. RESULTS: There was high interindividual variability in Lisch nodule burden. Lisch nodules were primarily located in the inferior hemifield (half) of the iris, regardless of its color (P = 3.0 x 10(-20)). Light irides harbored significantly more Lisch nodules than dark irides (P = 4.8 x 10(-5)). There was no statistically significant correlation of Lisch nodule burden to lifetime sunlight exposure "dose" or NF1 neurocutaneous severity. CONCLUSIONS: The difference in Lisch nodule burden between the superior and inferior iris hemifields is most likely due to the sunlight-shielding effects on the superior half by periocular structures. The difference in Lisch nodule burden between light and dark irides is probably due to the photoprotective effects of pigmentation. The genes underlying the control of iris color may thus be viewed as modifiers of severity of Lisch nodule burden in NF1. Given the role of UV radiation and, presumably, DNA damage in Lisch nodule pathogenesis, "benign tumor of the iris," not "hamartoma," may be a better descriptor.

Histopathology of a functioning mitomycin-C trabeculectomy.

The ideal trabeculectomy bleb is diffuse, normally vascularized and characterized by microcystic change in the overlying conjunctiva. We compare and contrast the histopathology of a normally functioning mitomycin-C trabeculectomy site obtained from an eye enucleated for iris melanoma with abnormal blebs discussed in the literature. Representative sections of the normally functioning bleb were examined under the light microscope. The conjunctiva is composed of a uniform three-layered non-keratinizing stratified squamous epithelium overlying a single layer of oedematous basal cells. The conjunctival stroma consisted of loose connective tissue, traversed by capillaries and scattered small cystic spaces lined by endothelial cells. There were no goblet cells and few inflammatory cells and fibroblasts. The scleral trapdoor was evident as a cleft in the scleral wall in communication with the anterior chamber at the surgically created sclerostomy. Because the histopathological findings in our case correlate well with this clinical appearance, we conclude that whereas augmentation with anti-metabolites, such as mitomycin-C, can be associated with significantly altered conjunctival histopathology and consequent hypotony, but, if used carefully, normal architecture is conserved.

Eye disorders in neurofibromatosis (NF1).

Neurofibromatosis type 1 (NF 1) is an autosomal dominant disorder with high index of spontaneous mutations and extremely varied and impredictible clinical manifestations. The aim of this work was to give an account of eye disorders in NF1. 132 patients of age 0-16 years with NF1 were followed up for 15 years. They were checked repeatedly for ophthalmologic disorders. Frequent eye disorders were: Lisch nodules (Iris hamartomas, IH) 78%, hyperthelorism 19.7%, bulbomotoric disorders 15.9%, disorders of the optic disc 16.7% and optic gliomas (18.9%). The highest incidence of eye disorders by NF1 patients showed Lisch nodules (IH). Its ease of clinical recognition and if present with other diagnostic signs (for instance café au lait patches) could be deemed as reliable diagnostic criterion of NF1 in childhood.

Lisch nodules after trabeculectomy.

The development of Lisch nodules in an eye that had undergone trabeculectomy with mitomycin C is described. Complete ophthalmologic examinations and genetic testing of a 12-year-old boy were performed. Lisch nodules can develop after trabeculectomy without the systemic manifestations of neurofibromatosis type 1.

Characteristics of Lisch nodules in patients with neurofibromatosis type 1.

PURPOSE: To assess the prevalence and location of Lisch nodules among patients with neurofibromatosis type 1. PATIENTS AND METHODS: This was a prospective observational case series in which 369 consecutive patients from a neurofibromatosis clinic participated. Predetermined inclusion and exclusion criteria were applied to these participants. The presence of Lisch nodules was determined by one of the authors (SMC). The percentage of patients with neurofibromatosis type 1 with Lisch nodules was calculated. Lisch nodules were characterized as being distributed superiorly, inferiorly, or equally in each eye. The percentage of eyes in each group was ascertained. RESULTS: Among patients of all ages with neurofibromatosis type 1, 63.2% had Lisch nodules, whereas 92% of postpubertal patients had Lisch nodules. Among eyes with Lisch nodules, 80% had an inferior distribution. CONCLUSIONS: This study corroborated previously reported data regarding the prevalence of Lisch nodules in patients with neurofibromatosis type 1 and found that Lisch nodules were predominantly located inferiorly on the iris. The authors propose that exposure to sunlight may be the mechanism for this distribution of hamartomatous nodules.

Sun exposure predicts risk of ocular melanoma in Australia.

Previous studies examining sun exposure and ocular melanoma have produced inconsistent results. We investigated this association in a population-based case-control study in Australia. Cases (n = 290) aged 18-79 years were diagnosed between January 1996 and July 1998. Controls (n = 893) were randomly selected from the electoral rolls and frequency-matched to cases by age, sex and state. A self-administered questionnaire and a telephone interview measured sun exposure on weekdays and weekends at 10, 20, 30 and 40 years of age and over the whole of life for specific jobs and recreations. Multivariate logistic regression models of ocular melanoma and sun exposure contained age, sex, region of birth, eye color and measures of ocular and cutaneous sun sensitivity as covariates. Choroid and ciliary body melanoma (n = 246) was positively associated with time outdoors on weekdays and, less persuasively, total time outdoors but not ambient solar irradiance. Odds ratios increased with increasing exposure to OR 1.8 (95% confidence interval 1.1-2.8) for the highest quarter of sun exposure on weekdays up to 40 years of age for men and women together. The strongest positive associations were for total exposure up to 40 years of age, lifetime occupational exposure and total exposure at about 20 years of age in men; all had odds ratios between 2 and 3 in the highest exposure categories. There was inconclusive evidence for an association between sun exposure and iris (n = 25) or conjunctival (n = 19) melanomas. Sun exposure is an independent risk factor for choroidal and ciliary body melanoma in Australia.

Posttransplantation lymphoproliferative disorder initially seen as iris mass and uveitis.

Primary ocular posttransplantation lymphoproliferative disorder is rare. Epstein-Barr virus is implicated as the cause as a result of systemic immunosuppression after transplant surgery. We studied a patient who developed ocular posttransplantation lymphoproliferative disorder after orthotopic liver transplantation. Slitlamp and light microscopic photographs confirmed the diagnosis.

Iris lymphoma in a pediatric cardiac transplant recipient: clinicopathologic findings.

PURPOSE: To report the unusual presentation of a confirmed iris lymphoma in the setting of posttransplant lymphoproliferative disorder. DESIGN: Case report with clinicopathologic findings. METHODS: The medical record was reviewed for clinical manifestations, course of disease, and pathologic and radiologic findings. RESULTS: A 4-year-old girl who had undergone a cardiac transplant at 3 months of age was found to have unilateral iris lesions associated with granulomatous uveitis. Her condition was unresponsive to local and systemic steroids, so she underwent an iris biopsy that was found to contain a B cell-derived monoclonal lymphoproliferation. Treatment with systemic chemotherapy including cyclophosphamide and prednisone resulted in a transient, partial response. Localized radiotherapy induced total regression of the iris lesions. She continues to be observed and has been free of recurrence or metastasis for the past 12 months. CONCLUSIONS: Because of the increased use of organ transplantation, eye care specialists should consider the diagnosis of intraocular lymphoma when confronted with uveitis-like syndrome unresponsive to topical steroid therapy. Although there are numerous treatment options for intraocular lymphoma, radiation therapy was found to be effective in the treatment of this case.

Primary intraocular posttransplantation lymphoproliferative disorder.

We report a case of posttransplantation lymphoproliferative disorder manifesting as an isolated, unilateral iris tumor. A 2-year-old boy who had undergone liver transplantation for biliary atresia at age 4 months was seen with a 2-month history of an enlarging iris nodule. Histopathologic examination of the iris lesion demonstrated a mixed population of lymphoid cells. To our knowledge, this is the youngest patient with posttransplantation lymphoproliferative disorder isolated to the eye.