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Immunophenotypic results for ECVL and IH demonstrated no overlapping staining patterns. Infantile hemangioma had the classical architecture of capillaries. Because of the constant presence of mural smooth muscle, it was concluded that ECVL is an accurate and descriptive term. However, desmin negativity in ECVL indicates myofibroblastic differentiation rather than full-fledged smooth muscle differentiation. Infantile hemangioma may display ectatic channels as the lesion ages but does not acquire multilaminar smooth muscle walls. Its pericytes lack cytoplasmic filaments and desmin reactivity but are SMA-positive because of the presence of poorly polymerized actin in the cytosol. In IH, Ki-67 positivity was observed in the endothelial cells of the solid and more ectatic regions. In contrast, the virtual absence of Ki-67 positivity in ECVL lends further support for the interpretation that it is more closely related to a malformation than a benign neoplasm.

Purpose To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Design Retrospective clinicopathologic study. Methods The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher's exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Results Increasing grade of anaplasia was associated with decreased overall survival (p=0.003) and increased risk of metastasis (p=0.0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (p<0.0001), choroidal invasion (p=<0.0001), and anterior segment invasion (p=0.04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (p=0.01 for metastasis, p=0.03 for death) but anaplasia was not (p=0.63 for metastasis, p=0.30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (p=0.0004) and death (p=0.01). Conclusion Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy.

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation.

In the past 10 years, the management strategy for retinoblastoma has significantly changed, shifting toward local chemotherapy and away from systemic chemotherapy. Innovations in the field of molecular biology and the development of targeted therapies have led to improvements in survival rates and ocular salvage for this disease. However, the need still exists to further assess the long-term effects of such directional changes in Therapy.

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are able to distinguish among anaplastic grades and thus predict high- versus low-risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia also would yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.

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