Gain of Chromosome 6p Correlates with Severe Anaplasia, Cellular Hyperchromasia, and Extraocular Spread of Retinoblastoma.

Purpose: Gain of chromosome 6p has been associated with poor ocular survival in retinoblastoma and histopathologic grading of anaplasia with increased risk of metastatic spread and death. This study examined the correlation between these factors and other chromosomal abnormalities as well as results of whole genome sequencing, digital morphometry, and progression-free survival. Design: Retrospective cohort study from 2 United States tertiary referral centers. Participants: Forty-two children who had undergone enucleation for retinoblastoma from January 2000 through December 2017. Methods: Status of chromosomes 6p, 1q, 9q, and 16q was evaluated with fluorescence in situ hybridization, the degree of anaplasia and presence of histologic high-risk features were assessed by ocular pathologists, digital morphometry was performed on scanned tumor slides, and whole genome sequencing was performed on a subset of tumors. Progression-free survival was defined as absence of distant or local metastases or tumor growth beyond the cut end of the optic nerve. Main Outcome Measures: Correlation between each of chromosomal abnormalities, anaplasia, morphometry and sequencing results, and survival. Results: Forty-one of 42 included patients underwent primary enucleation and 1 was treated first with intra-arterial chemotherapy. Seven tumors showed mild anaplasia, 19 showed moderate anaplasia, and 16 showed severe anaplasia. All tumors had gain of 1q, 18 tumors had gain of 6p, 6 tumors had gain of 9q, and 36 tumors had loss of 16q. Tumors with severe anaplasia were significantly more likely to harbor 6p gains than tumors with nonsevere anaplasia (P < 0.001). Further, the hematoxylin staining intensity was significantly greater and that of eosin staining significantly lower in tumors with severe anaplasia (P < 0.05). Neither severe anaplasia (P = 0.10) nor gain of 6p (P = 0.21) correlated with histologic high-risk features, and severe anaplasia did not correlate to RB1, CREBBP, NSD1, or BCOR mutations in a subset of 14 tumors (P > 0.5). Patients with gain of 6p showed significantly shorter progression-free survival (P = 0.03, Wilcoxon test). Conclusions: Gain of chromosome 6p emerges as a strong prognostic biomarker in retinoblastoma because it correlates with severe anaplasia, quantifiable changes in tumor cell staining characteristics, and extraocular spread.

Absence of lenadogene nolparvovec DNA in a brain tumor biopsy from a patient in the REVERSE clinical study, a case report.

BACKGROUND: Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally-inherited mitochondrial disease that primarily affects retinal ganglion cells (RGCs) and their axons in the optic nerve, leading to irreversible, bilateral severe vision loss. Lenadogene nolparvovec gene therapy was developed as a treatment for patients with vision loss from LHON caused by the most prevalent m.11778G > A mitochondrial DNA point mutation in the MT-ND4 gene. Lenadogene nolparvovec is a replication-defective recombinant adeno-associated virus vector 2 serotype 2 (AAV2/2), encoding the human wild-type MT-ND4 protein. Lenadogene nolparvovec was administered by intravitreal injection (IVT) in LHON patients harboring the m.11778G > A ND4 mutation in a clinical development program including one phase 1/2 study (REVEAL), three phase 3 pivotal studies (REVERSE, RESCUE, REFLECT), and one long-term follow-up study (RESTORE, the follow-up of REVERSE and RESCUE patients). CASE PRESENTATION: A 67-year-old woman with MT-ND4 LHON, included in the REVERSE clinical study, received a unilateral IVT of lenadogene nolparvovec in the right eye and a sham injection in the left eye in May 2016, 11.4 months and 8.8 months after vision loss in her right and left eyes, respectively. The patient had a normal brain magnetic resonance imaging with contrast at the time of diagnosis of LHON. Two years after treatment administration, BCVA had improved in both eyes. The product was well tolerated with mild and resolutive anterior chamber inflammation in the treated eye. In May 2019, the patient was diagnosed with a right temporal lobe glioblastoma, IDH-wildtype, World Health Organization grade 4, based on histological analysis of a tumor excision. The brain tumor was assessed for the presence of vector DNA by using a sensitive validated qPCR assay targeting the ND4 sequence of the vector. CONCLUSION: ND4 DNA was not detected (below 15.625 copies/µg of genomic DNA) in DNA extracted from the brain tumor, while a housekeeping gene DNA was detected at high levels. Taken together, this data shows the absence of detection of lenadogene nolparvovec in a brain tumor (glioblastoma) of a treated patient in the REVERSE clinical trial 3 years after gene therapy administration, supporting the long-term favorable safety of lenadogene nolparvovec.

Clinical and radiographic characteristics of diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma: a single institution review.

PURPOSE: Genetic analyses of gliomas have identified key molecular features that impact treatment paradigms beyond conventional histomorphology. Despite at-times lower grade histopathologic appearances, IDH-wildtype infiltrating gliomas expressing certain molecular markers behave like higher-grade tumors. For IDH-wildtype infiltrating gliomas lacking traditional features of glioblastoma, these markers form the basis for the novel diagnosis of diffuse astrocytic glioma, IDH-wildtype (wt), with molecular features of glioblastoma (GBM), WHO grade-IV (DAG-G). However, given the novelty of this approach to diagnosis, literature detailing the exact clinical, radiographic, and histopathologic findings associated with these tumors remain in development. METHODS: Data for 25 patients matching the DAG-G diagnosis were obtained from our institution's retrospective database. Information regarding patient demographics, treatment regimens, radiographic imaging, and genetic pathology were analyzed to determine association with clinical outcomes. RESULTS: The initial radiographic findings, histopathology, and symptomatology of patients with DAG-G were similar to lower-grade astrocytomas (WHO grade 2/3). Overall survival (OS) and progression free survival (PFS) associated with our cohort, however, were similar to that of IDH-wt GBM, indicating a more severe clinical course than expected from other associated features (15.1 and 5.39 months respectively). CONCLUSION: Despite multiple features similar to lower-grade gliomas, patients with DAG-G experience clinical courses similar to GBM. Such findings reinforce the need for biopsy and subsequent analysis of molecular features associated with any astrocytoma regardless of presenting characteristics.

Functioning Crooke Cell Adenomas: Case Series and Literature Review.

BACKGROUND: Crooke cell adenomas (CCAs) are rare, potentially aggressive pituitary adenomas. Data regarding prevalence and clinical course are sparse. METHODS: We performed a retrospective review of 59 consecutive functioning corticotroph adenomas operated on between October 2017 and November 2020 and a literature review of CCA publications since 1991. RESULTS: The prevalence of CCAs among functioning corticotroph adenomas at our institution was 8.5% (5/59). In the 4 other surgical case series, prevalence of CCAs was 0%-6.8%. Our patients (4 women and 1 man, mean age 46 ± 11 years) presented with hypercortisolism (3/5), with vision loss (1/5), and incidentally (1/5). All patients had elevated adrenocorticotropic hormone (151 ± 54 pg/mL) and urinary free cortisol (830 ± 796.5 µg/day). Radiologically, 3 tumors were macroadenomas and 2 had cavernous sinus invasion. All patients achieved biochemical remission at 3 months postoperatively. One patient with a giant pituitary adenoma underwent fractionated radiation for residual tumor. During follow-up (range, 3.1-31.0 months), no patients had evidence of radiological or biochemical recurrence. The literature review identified 22 functioning corticotroph adenomas with outcome data. Additional treatments included reoperation (50%), radiation (59%), bilateral adrenalectomy (23%), and temozolomide (36%). CONCLUSIONS: We found a higher CCA prevalence among functioning adrenocorticotropic hormone adenomas after implementation of the 2017 World Health Organization classification. In our series and the literature, most CCAs were macroadenomas with high adrenocorticotropic hormone levels. Postoperative outcomes were excellent in our series, while some cases from the literature were refractory to standard treatments. Larger clinical and molecular studies are needed to identify patients at risk.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Orbit: Three Cases and Review of the Literature.

The authors present 3 patients from this retrospective case series to review the clinical findings, imaging, pathology, and treatment of orbital atypical lipomatous tumor/well-differentiated liposarcoma. Pathology of biopsy specimens ranged from spindle cell proliferations mimicking neurofibroma to proliferations of well-differentiated adipocytes. Immunohistochemical stains were positive for murine double minute 2 in 1 case, and fluorescent in situ hybridization showed amplification of murine double minute 2 in 2 cases. Treatments ranged from serial debulking, proton beam irradiation, and exenteration. None of the patients developed metastases. A literature review supported the low-grade nature of this lesion. Orbital atypical lipomatous tumor/well-differentiated liposarcoma is a low-grade, indolent liposarcoma that may be locally invasive. The histologic diagnosis is enhanced with immunohistochemical staining for murine double minute 2 and fluorescent in situ hybridization analysis for amplification of murine double minute 2. Although treatment may vary according to the individual, conservative therapies may be attempted prior to radical surgery.

High-Grade Sarcoma Arising within a Previously Irradiated Vestibular Schwannoma: A Case Report and Literature Review.

BACKGROUND: Vestibular schwannomas are benign tumors of the cerebellopontine angle that are often treated with radiation therapy. Radiation therapy maintains good tumor control rates but involves a small risk of radiation-induced malignancies. We present a case of high-grade sarcoma arising within a previously irradiated vestibular schwannoma and a literature review of this rare but important clinical entity. METHODS: A 66-year-old woman presented with rapid clinical and radiographic deterioration 17 years after receiving stereotactic radiosurgery for vestibular schwannoma. After resection, pathology revealed a high-grade sarcoma arising within a conventional schwannoma. After further decline and tumor growth, the patient died of her disease 7 months postoperatively. Literature review was performed using PubMed and EMBASE databases and key words "vestibular schwannoma," "acoustic," "triton," "malignant," "sarcoma," "malignant peripheral nerve sheath tumor," "radiation," and "radiosurgery." All previous cases and the clinical circumstances related to these radiation-induced malignancies were assessed and quantified. RESULTS: The systematic review yielded 20 prior cases of radiation-induced malignant transformation of a vestibular schwannoma in patients without neurofibromatosis. Most tumors (60%) transformed into malignant nerve sheath tumors. At the time of presentation, 70% of patients had new cranial neuropathies, and all had evidence of tumor growth with brainstem compression. Prognosis was poor with mean time to death of 7.6 months. CONCLUSIONS: Radiation-induced malignant transformation of vestibular schwannomas is a rare but important clinical entity. Given its scarcity, the risk of malignancy should not sway initial management, but rapid clinical deterioration and radiographic growth during follow-up should prompt consideration of malignant transformation.

Digital morphometry of tumor nuclei correlates to BAP-1 status, monosomy 3, gene expression class and survival in uveal melanoma.

Cytologic features such as the shape and size of tumor cells can predict metastatic death in uveal melanoma and other cancers but suffer from poor reproducibility. In this study, we investigate the interobserver concordance of digital morphometry, and correlate the results with BRCA associated protein-1 (BAP-1) expression and BAP-1 gene mutation status, monosomy 3, gene expression classifications and patient survival in uveal melanoma. The average number of cells analyzed in each of 107 tumors, was 1957 (SD 349). Mean time consumption was less than 2.5 min per tumor. Identical morphometric classification was obtained for ≥85% of tumors in all twelve evaluated morphometric variables (κ 0.70-0.93). The mean nucleus area, nucleus perimeter, nucleus max caliper and nucleus to cell area ratio were significantly greater in tumors with low BAP-1 expression and gene expression class 2. Patients had significantly shorter survival if their tumors had low BAP-1 (Log-Rank p = 0.002), gene expression class 2 (p = 0.004), long nucleus perimeters (p = 0.031), long nucleus max calipers (p = 0.029) and high mean nucleus to cell area ratios (p = 0.041) as defined in a training cohort and then tested in a validation cohort. Long nucleus perimeters and long nucleus max calipers correlated with monosomy 3 (Pearson Chi-Square p = 0.006 and p = 0.009, respectively). Long nucleus perimeters also correlated with BAP-1 mutation (p = 0.017). We conclude that digital morphometry can be fast and highly reproducible, that for the first time, morphometry parameters can be objectively quantitated in thousands of cells at a time in sub-µm resolutions, and that variables describing the shape and size tumor nuclei correlate to BAP-1 status, monosomy 3, gene expression class as well as patient survival.

In situ analysis of Her2 DNA and RNA in retinoblastoma and adjacent retina.

Retinoblastoma (RB) is an ocular tumor of early childhood. Current treatments attempt to preserve visual function, but may spare chemoresistant tumor cells. One potential therapeutic target for RB is HER2, (ERBB2), expressed in RB in truncated form. In this study, we tested the hypothesis that Her2 DNA and RNA are expressed in RB tumors and adjacent retina. We examined 24 human RB tumors as well as normal-appearing adjacent retinal tissues for Her2 DNA and RNA expression by in situ hybridization. We also examined 28 RB tumors for HER2 protein immunoreactivity. 21/22 RB tumors expressed Her2 DNA and 14/19 tumors expressed Her2 RNA. In 17 paired cases, there were three cases in which Her2 DNA was detected, but not RNA. We also saw Her2 RNA signal in six instances of "normal" adjacent retinal tissue. Heterogeneous HER2 protein expression in specific tumor regions also was confirmed by quantitative HER2 immunohistochemistry. In summary, Her2 DNA and RNA are expressed in many RB tumors, and in some adjacent ocular tissues, with hetereogenous protein expression throughout. These results may provide important insights regarding RB tumor progression, and drug targeting approaches designed to spare the eye, preserve vision and improve quality of life for RB patients.

Comparing breast biomarker status between routine immunohistochemistry and FISH studies and Oncotype DX testing, a study of 610 cases.

INTRODUCTION: Oncotype DX (ODX) testing uses reverse transcription polymerase chain reaction (RT-PCR) to predict distant recurrence rate of estrogen receptor positive (ER+)/HER2-negative (HER2-)/lymph node-negative (LN-) breast cancers. ODX also reports the status of breast cancer biomarkers, ER, progesterone receptor (PR), and HER2. This study examined the discrepancy rate of breast cancer biomarker status as reported by ODX vs routinely used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. METHODS: A total of 610 breast cancer cases (609 ER+ and 1 ER-negative (ER-) by IHC) with ODX reports were reviewed. ER, PR, and HER2 status from ODX reports were compared with results from IHC and FISH studies. RESULTS: There was an overall high concordance rate between IHC and ODX for ER expression (603/610 concordant, 98.9%) and moderate concordance for PR expression (549/610 concordant, 90%). Of the seven ER-discrepant cases, six were positive by IHC but negative by ODX. Of the 61 PR-discrepant cases, 41 were positive by IHC but negative by ODX. Of the 610 cases, 568 had HER2 results reported by ODX. Five cases were HER2+ by IHC/FISH (0.88%). One of these five cases was reported as HER2+, two as HER2-, and two as HER2-equivocal by ODX. None of the cases that were HER2- or equivocal by IHC/FISH was reported as HER2+ by ODX. CONCLUSIONS: There is good concordance between IHC and ODX for ER and PR expression, but IHC is more sensitive. The significant discordance in HER2+ cases may discourage reporting HER2 status by ODX testing.

Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.

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.

Evaluation of Prognosis in Hormone Receptor-Positive/HER2-Negative and Lymph Node-Negative Breast Cancer With Low Oncotype DX Recurrence Score.

INTRODUCTION: Hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancers without lymph node metastasis have good prognosis. We compared the prognosis of hormone receptor-positive, HER2-negative, lymph node-negative cancers with Oncotype DX score ranges of 1 to 10 (1-10 group) and 11 to < 18 (11-18 group). PATIENTS AND METHODS: A total of 107 cases in the 1-10 group and 225 cases in the 11-18 group were reviewed. All patients received surgery. The use of chemotherapy, radiotherapy, and endocrine therapy, and overall survival (OS), disease-free survival (DFS), and distant metastasis were compared between groups. RESULTS: There were no statistical differences in the use of chemotherapy (5.05% vs. 6.05%, P = .724) or radiotherapy (52.53% vs. 59.07%, P = .276) between the 1-10 group and the 11-18 group, respectively. The median OS and DFS were 47 and 45 months, respectively, in the 1-10 group, and 49 and 48 months in the 11-18 group. No significant difference was seen in OS (P = .995), DFS (P = .148), or rates of metastasis (P = .998). The 11-18 group had more death events and distant metastasis (death, 5 events; recurrence, 2 events; metastasis, 2 events) than the 1-10 group (death, 0 events; recurrence, 4 events; metastasis, 0 events). The majority of recurrences seen in both groups were in young patients who failed to comply with their endocrine therapy regimen. CONCLUSION: Patients in both the 1-10 group and the 11-18 group had good prognoses. Those who experienced recurrence were more likely to be premenopausal and to have failed to comply with the recommended endocrine therapy regimen. Endocrine therapy remains important in these patients.

Comparative outcomes and toxicities for ruthenium-106 versus palladium-103 in the treatment of choroidal melanoma.

For the treatment of choroidal melanoma, palladium-103 (Pd) and ruthenium-106 (Ru) plaque brachytherapy shows reduced toxicity compared with the historical standard iodine-125. No report has directly compared the clinical outcomes between Pd and Ru, and the reasons for the selection of one over the other remain purely theoretical. Patients with choroidal melanoma with apical tumor height up to 5 mm were included. Patients from Emory University were treated with Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. Pd patients (n=124) and Ru patients (n=42) had a median follow-up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes, but Ru had lower grades of retinopathy (P=0.006). Pd was associated with worse VA preservation (≥20/40) by year 3 (odds ratio: 3.8; 95% confidence interval: 1.01-14.31, P=0.048). Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (hazard ratio: 0.10; 95% confidence interval: 0.02-0.38; P<0.001). Ru had lower grades of radiation retinopathy and improved long-term VA preservation, but also inferior DMFS, compared with Pd. Because of the inherent limitations of a retrospective analysis, the significance of the inferior DMFS for Ru remains unclear, although the suggestion of a slight inferiority in terms of DMFS for Ru is consistent with the other limited literature. On the basis of this study, we believe that both radioisotopes remain appropriate for the treatment of small choroidal melanomas up to 5 mm in apical height.

Conjunctival Squamous Cell Carcinoma with Corneal Stromal Invasion in Presumed Pterygia: A Case Series.

AIM: To describe 4 cases of conjunctival squamous cell carcinoma (SCC) with corneal stromal invasion. METHODS: Retrospective, clinicopathologic case series. RESULTS: All patients had prior resections of presumed pterygia. The degree of corneal involvement dictated the extent of surgical management. One eye with localized invasion was treated with lamellar keratoplasty and plaque brachytherapy. Another case with widespread invasion warranted penetrating keratoplasty and eventual enucleation. Two cases were treated medically prior to surgical intervention: one with localized invasion was treated with topical interferon and retinoic acid; another with significant inflammation was treated with doxycycline and fluorometholone. The patient who underwent keratoplasty and brachytherapy had no recurrence after 7 years of follow-up. Those initially treated medically had resections of recurrence but ultimately required enucleation. Histologically, specimens demonstrated SCC invading the deep corneal stroma, with 2 tumors of the mucoepidermoid type. CONCLUSIONS: This series demonstrates the importance of maintaining clinical suspicion of conjunctival squamous neoplasia in pterygia. We recommend that all excised pterygia be submitted for histopathologic evaluation and be carefully evaluated for dysplasia and variants of SCC associated with increased risk of intraocular invasion. Undetected ocular surface squamous neoplasia may give rise to potentially vision- and eye-threatening invasive corneal SCC.

Updates in ophthalmic pathology.

Ophthalmic pathology has a long history and rich heritage in the field of ophthalmology. This review article highlights updates in ophthalmic pathology that have developed significantly through the years because of the efforts of committed individuals and the confluence of technology such as molecular biology and digital pathology. This is an exciting period in the history of ocular pathology, with cutting-edge techniques paving the way for new developments in diagnostics, therapeutics, and research. Collaborations between ocular oncologists and pathologists allow for improved and comprehensive patient care. Ophthalmic pathology continues to be a relevant specialty that is important in the understanding and clinical management of ocular disease, education of eye care providers, and overall advancement of the field.

Proliferative Vitreoretinopathy in Treated Retinoblastoma.

OBJECTIVE: To evaluate the clinical and histopathologic characteristics of patients who develop proliferative vitreoretinopathy after retinoblastoma treatment. DESIGN: Retrospective review of three cases of proliferative vitreoretinopathy (PVR) that developed after successful treatment of retinoblastoma from 2003 to 2015. SUBJECTS: Three patients with treated retinoblastoma who developed severe PVR and required enucleation. METHODS: Review of clinical charts, fundus drawings, Ret-Cam 3 images, and histopathology specimens. MAIN OUTCOME MEASURES: Clinical and histopathologic characterization of PVR in treated retinoblastoma. RESULTS: Three patients developed severe PVR after sequential thermal laser combined with systemic chemotherapy for retinoblastoma. At presentation patients were 6, 7, and 9 months of age, and all had bilateral retinoblastoma. Time to development of proliferative tissue was 9, 12, and 20 months after initial treatment. Proliferation was characterized by progressive growth of white vascularized tissue with associated traction on the retina and sometimes hemorrhage. All patients underwent enucleation. Histopathologic evaluation revealed treated retinoblastoma tumor with a Type 3 regression pattern, pre- and subretinal fibrovascular tissue consistent with PVR, and reactive changes in the retinal pigment epithelium. None of the patients developed recurrence of retinoblastoma or systemic metastasis. CONCLUSION: PVR uncommonly develops after successful treatment of retinoblastoma and may result in traction or rhegmatogenous retinal detachment along with vitreous hemorrhage. Early stages of proliferation may be difficult to distinguish from recurrent tumor. Enucleation may be required due to poor vision and inability to adequately monitor for tumor recurrence.

Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): A Case Report.

PURPOSE: To report the clinical and histopathological findings of a reactive retinal astrocytic tumor (RRAT) that progressed to massive retinal gliosis. OBSERVATIONS: The patient presented with an elevated, white-yellow retinal mass and extensive retinal exudation in the left eye. Progressive enlargement of the mass and proliferative vitreoretinopathy eventually led to phthisis bulbi and enucleation. Histologically, the mass showed a predominant astrocytic component with intense glial fibrillary acidic protein staining, hyperplasia, fibrous metaplasia, and osseous metaplasia of the retinal pigment epithelium. The Ki-67 proliferative index was <5%, and few scattered vascular channels were observed. CONCLUSIONS AND IMPORTANCE: These findings show that this tumor is the result of a reactive glial process rather than of neoplastic vascular proliferation. Massive retinal gliosis probably represents the advanced stage of RRAT.

Visual acuity, oncologic, and toxicity outcomes with 103Pd vs. 125I plaque treatment for choroidal melanoma.

PURPOSE: To evaluate outcomes of choroidal melanoma patients treated with 125I or 103Pd plaque brachytherapy. METHODS AND MATERIALS: From 1993 to 2012, our institution treated 160 patients with 103Pd (56.1%) and 125 patients with 125I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics. RESULTS: Median followup was longer for 125I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, 103Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3-T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both 103Pd and 125I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125I with 107 103Pd patients. 103Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103Pd than 125I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA. CONCLUSIONS: Both 125I and 103Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103Pd.

Atypical pituitary adenoma with orbital invasion: Case report and review of the literature.

Pituitary adenoma invasion into the orbit is a rare phenomenon with only 22 cases, including the present case, in the literature. Our case is a 31-year-old man who presented with biopsy-proven atypical pituitary adenoma invading the right orbit after a prior resection. We compare his clinical course with previous cases and discuss clinical features, radiological features, management considerations, histologic features, and prognosis. Cases are organized by specific pituitary tumor type to aid in determining appropriate management. Early surgical intervention is the key, especially in the setting of pathologic features indicating aggressive tumor behavior or worsening visual function but is generally not indicated in prolactin-secreting adenomas that may respond to medical therapy. The role of radiation therapy is not fully established; however, it should be strongly considered in conjunction with or after surgery, especially in cases where complete resection is not achieved or histological and molecular analyses indicate a high likelihood of recurrence. More uniform and comprehensive data about management and outcomes are needed to determine the optimal treatment approach for this rare entity.

DISTINCTIVE WHITE FUNDUS LESIONS IN FAMILIAL EXUDATIVE VITREORETINOPATHY: A NEWLY CHARACTERIZED CLINICAL FEATURE.

PURPOSE: To report a novel clinical finding associated with familial exudative vitreoretinopathy in three patients using fundus photography, fluorescein angiography, and histopathology. METHODS: Observational case series of three patients with familial exudative vitreoretinopathy, an ophthalmic examination with fundus photography, and fluorescein angiography were used to document clinical findings between January 2007 and January 2015. Surgical specimens from one case were examined using standard histopathologic techniques, as well as transmission electron microscopy and energy dispersive x-ray analysis. RESULTS: Distinctive white preretinal granules were noted in all cases and were found to be extramacular in location. Histopathology in one case revealed the granules to be crystalline structures with a regular pattern evident on higher magnification. The chemical constitution was found to be carbon, oxygen, and fluorine. CONCLUSION: Our case series represents the first description of white preretinal granules in association with familial exudative vitreoretinopathy. The authors have not seen these granules in other forms of retinopathy and their presence may aid in differentiating this disease from other entities.