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Secondary tumors of the optic nerve are more common than primary optic nerve tumors. The involvement of the optic nerve may arise from direct invasion from intraocular malignancies, from hematopoietic malignancy, from meningeal carcinomatosis, or from distant primary tumors. Orbital tumors rarely invade the optic nerve, and brain tumors involve it only in their late stages.
We describe two unusual young patients with intraocular lymphoma who presented clinically with "retinal vasculitis." Brain biopsy specimens in both showed an angiocentric pattern of lymphocytic infiltration. Immunohistochemical studies were positive for T-cell markers. Both the retinal and the brain blood vessels were thus a preferential site of appearance of the malignant T-cells. Both cases responded favorably to aggressive chemotherapy with long-term survival. In the world's literature, there are 57 cases of intraocular lymphoma in which cell surface-marker studies were performed; of these, 53% proved to be B-cell lymphomas and 21% to be T-cell lymphomas. As more cases of intraocular lymphoma are studied with cell-typing and as our histochemical techniques improve, a correlation between the systemic and ocular findings and the cell type may be revealed.
Patients with retinoblastoma have an increased risk of developing second primary tumors. Only a few examples of sinonasal small cell neoplasms developing after radiation therapy for retinoblastoma have been reported. We report one such case that developed 18 years after treatment for retinoblastoma. Histologic examination revealed a small, blue, round cell tumor without rosettes or cytoplasmic glycogen. Immunohistochemically, the tumor cells were positive for neuron-specific enolase, synaptophysin, and S-100 protein, but negative for epithelial and mesenchymal markers, suggesting that this was a primitive neuroectodermal tumor. Cytogenetic studies of this tumor failed to reveal the chromosome 13 abnormality typical of retinoblastoma and the t(11:22) translocation typical of the group of peripheral neuroepitheliomas.
Deoxyribonucleic acid (DNA) ploidy was quantified in 84 ocular melanomas (median follow-up, 11-years) by flow cytometry, CAS 200 interactive image analysis, and Pathology Image Processing Environment (PIPE; Department of Quantitative Pathology, Free University, Amsterdam, The Netherlands) automatic image analysis (75). Overall, 32.1% of the melanomas were aneuploid, 2.3% were tetraploid, and 66.6% were diploid. Pathology Image Processing Environment analysis estimated DNA ploidy in 12 tumors that were unprocessable by flow cytometry. Of 10 tumors that were diploid by flow cytometry, PIPE detected stemline aneuploidy in five and some aneuploid cells in five more. Seven tumors were aneuploid by PIPE but diploid by CAS 200, five of which contained occasional DNA aneuploid cells on the CAS 200 histograms. Pathology Image Processing Environment analysis quantified tumor samples with an average of 500 (250 to 1,050) cells in less than 10 minutes. All cells classified as spindle A according to the Callender system (more than 10,000) were diploid. Spindle B and epithelioid cells occupied both diploid and aneuploid peaks on the DNA histograms. Dioxyribonucleic acid variables did not correlate with established prognosticators, such as Callender cell type, largest tumor dimension, or glaucoma, nor did they reach significance by univariate and multivariate analyses. The value of these findings as a diagnostic support in uveal melanoma, particularly in combination with fine needle aspiration biopsy, is discussed.
Osseointegrated percutaneous implants were placed at different sites of the facial skeleton to improve the retention of facial prostheses. Based on four cases a new implant position in autogenous bone grafts for retention of orbital restorations is described. As a first step an autogenous iliac bone graft was transplanted into the orbit. After a minimum interval of 3 months endosseous implants were placed into the grafted bone in axial direction in the middle of the orbit. A third operation several months later uncovered the implants. Using single free-standing rare earth magnetic attachments the orbital episthesis or the eye prosthesis was reliably stabilized. In all cases the bone grafts were integrated at the host site. Nine implants with a follow-up period of 4-66 months have been placed of which one was lost. The patients experienced subjective and objective improvement. Indications and advantages of the method are discussed.
Normal skin fibroblasts from patients genetically predisposed for cancer express certain phenotypic properties usually associated with transformed cells, suggesting that these cells are engaged in a cancer progression process. Previously, we have shown that a subgenomic fraction, which we called Ta DNA ('tumor-activated DNA') was preferentially expressed in all human tumor cells (Hanania et al., Proc. Natl. Acad. Sci. U.S.A., 78 (1981) 6504-6508; Hanania et al, EMBO J., 2 (1983) 1621-1624). Here, we show that Ta DNA transcripts are present in Fanconi's anemia (FA) and retinoblastoma (Rb) fibroblasts, at a level hardly lower than in tumor cells. In contrast, a few Ta DNA transcripts can be detected in normal cells.
A clinical radiotherapeutic trial using heavy charged particles in the treatment of human cancers has accrued over 400 patients since 1975, 378 of whom were treated with particles and 28 with low LET photons as control patients. Heavy charged particle radiotherapy offers the potential advantages of improved dose localization and/or enhanced biologic effect, depending on particle selected for treatment. Target sites have included selected head and neck tumors, ocular melanomata, malignant gliomata of the brain, carcinoma of the esophagus, carcinoma of the stomach, carcinoma of the pancreas, selected juxtaspinal tumors and other locally advanced, unresectable tumors. A Phase III prospective clinical trial has been started in carcinoma of the pancreas using helium ions. Phase I-II studies are underway with heavier particles such as carbon, neon and argon ions in order to prepare for prospective Phase III trials. Silicon ions are also under consideration for clinical trial. These studies are supported by the United States Department of Energy and National Institutes of Health.
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PURPOSE: To study BCL10 expression in ocular adnexal lymphoma in the US population and its association with clinical outcomes. DESIGN: Institutional, retrospective study. METHODS: Immunohistochemistry was performed with antibody against BCL10 on two tissue microarray blocks that were constructed with paraffin-embedded tissues from the same cohort of 48 patients with ocular adnexal lymphomas. The main outcomes that were measured include extraorbital involvement, recurrence rate, and time to recurrence. The median length of the follow-up period was 40 months. RESULTS: Aberrant BCL10 expression (nuclear [moderate intensity] and cytoplasmic [weak to moderate intensity] staining) was observed in 10 of 33 cases (30.3%) of mucosa-associated lymphoid tissue (MALT) lymphoma, in 4 of 10 cases (40%) of follicular lymphoma (grade 1, 9 cases; grade 2, 1 case), in 0 of 2 cases of diffused large B-cell lymphoma, in 0 of 1 case of chronic lymphocytic leukemia/small lymphocytic lymphoma and in 1 of 1 case (100%) of mantle cell lymphoma. There were no differences in clinical parameters at examination (ie, average age, gender, site of occurrence, laterality, extraorbital involvement at diagnosis), recurrence rate, and time to recurrence for patients (MALT lymphoma or follicular lymphoma) with or without aberrant nuclear BCL10 expression. CONCLUSION: Aberrant BCL10 expression can occur in other types of ocular adnexal lymphomas besides MALT lymphoma. Ocular adnexal MALT lymphoma may have slightly lower frequency of aberrant BCL10 expression than gastric/pulmonary MALT lymphomas that have been reported in the literature. Furthermore, aberrant BCL10 nuclear expression in ocular adnexal lymphoma does not seem to correlate with clinical outcome. Further studies that include a larger number of cases and longer follow-up period are needed to confirm our observation.
PURPOSE: To investigate the feasibility of integrating molecular analysis into standard histopathology for lacrimal gland adenoid cystic carcinoma (ACC), and to gain insights into the molecular pathogenesis of this tumor and its response to intraarterial cytoreductive chemotherapy (IACC) that is of clinical use. DESIGN: A retrospective, comparative case series. METHODS: setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. intervention procedure: Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci was performed with 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serving as markers for the presence of gene deletion. main outcome measure: A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS: Allelic imbalance (loss of heterozygosity [LOH]) for microsatellite markers at 1p36 was the single most common site affected by imbalance in this series, followed by LOH in temporal sequence involving 9p21, 22q12, 10q23, and 9q22. CONCLUSIONS: Microdissection genotyping holds promise as a clinical tool in integrating molecular analysis into standard histopathology to advance the understanding of lacrimal gland ACC tumorigenesis. A unique time course for temporal mutation acquisition in ACC is proposed, consisting of 1p36 loss first. Allelic loss for microsatellite markers at 1p36 may be a common as well as an early event in ACC formation and progression.
Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma. The incidence of PIOL has increased in the past 20 years. PIOL often presents as chronic uveitis that is resistant to corticosteroid therapy. Diagnosing PIOL can be challenging and requires an expert pathologist. The treatment of PIOL is difficult because of its high recurrence rate and refractory nature. The objective for the future is to improve diagnostic techniques and therapeutic success while minimizing ocular toxicities.
Ongoing studies based on gene expression profile analysis using microarrays have provided preliminary evidence for significant molecular distinctions between primary central nervous system lymphoma (PCNSL) and nodal lymphomas of the large B-cell type. The application of array-based comparative genomic hybridization techniques attempts to identify genomic distinctions between PCNSL and nodal lymphomas and to identify the molecular markers that relate to prognosis. It is possible that insights gained from these studies will facilitate the development of targeted therapies, which address the fundamental genetic mutations that drive PCNSL and intraocular lymphoma growth.
PURPOSE: To evaluate the role of fluorine 18 deoxyglucose positron emission tomography (FDG PET) in the initial staging of ocular adnexal lymphoma (OAL). DESIGN: Retrospective nonrandomized case series. PARTICIPANTS: Eleven patients with OAL who underwent FDG PET at initial staging. METHODS: Retrospective review of all the clinical and imaging records, including computed tomography (CT) and FDG PET. MAIN OUTCOME MEASURES: The ability of PET studies to detect OAL and distant disease was compared with CT. RESULTS: Eleven patients with OAL who underwent FDG PET at initial staging were retrospectively reviewed having full access to their clinical and imaging data. Fluorine 18 deoxyglucose PET found distant disease in 5 of 6 lymphoma patients with systemic disease; 4 of these patients (66%) were upstaged, changing the clinical management. Orbital lesions were demonstrated in 3 of 11 patients, giving PET a sensitivity of 27% in the orbit and 83% systemically for detection of lymphoma. CONCLUSION: The ability of FDG PET to find systemic extranodal lymphomatous sites not detected with conventional imaging provides valuable information in OAL patients, which may result in important changes in staging and management. The technique does have limitations in detecting OAL compared with conventional imaging, possibly owing to background physiologic activity in the extraocular muscles in the orbit and the small volume of some orbital deposits.
BACKGROUND: The aim of this study was to evaluate early insertion of ocular prostheses for aesthetic rehabilitation after enucleation and review current methods of enucleation surgery. METHODS: Twelve patients with large intraocular malignancies were treated by enucleation with implant. At the end of surgery, a medium-size conformer was inserted onto the closed conjunctival wound (just before applying a pressure dressing). The pressure dressing was removed 3 to 5 days after surgery. Immediately after bandage removal, the patients saw themselves in a mirror and were offered placement of a relatively small ocular prosthesis. Patients were asked if they preferred their aesthetic appearance with or without the prosthesis. RESULTS: Eight patients (67%) tolerated introduction of the prosthesis at the time of removal of their pressure dressing (3 to 5 days after enucleation surgery). Because of discomfort, 4 were able to receive their prostheses at their second postoperative visit (day 12 or 13). The manipulation at prosthesis insertion and subsequent wearing was found to have no effect on wound closure, final prosthetic fittings, or movement of the permanent prosthesis. All patients were pleased with the cosmetic benefit afforded by early introduction of the prosthesis and preferred their appearance to that of their eye with the conformer. CONCLUSIONS: Early replacement of the conformer by an ocular prosthesis allows for cosmetic rehabilitation and improved quality of life.
INTRODUCTION: Ocular metastases are rare in patients with lung cancer, and exceptionally indicate the condition. EXEGESIS: We report 2 patients with symptomatic ocular metastases indicating lung adenocarcinoma, involving the choroid in the first case and the optic disc in the other, associated with other metastases. No improvement of visual acuity was observed after chemotherapy and radiotherapy. DISCUSSION: Ocular metastases may indicate lung cancer, and are usually associated with other metastatic sites. The global prognosis is poor but an early treatment should result in improvement of visual prognosis.
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