Immunology of intraocular tumors

The immune surveillance hypothesis was introduced over 30 years ago and proposed that neoplasms express novel antigens that subjected them to immune detection and elimination. In order for immune surveillance to be effective in controlling neoplasms, two requirements must be satisfied: 1) the tumor must arise in a body site that permits the induction the full array of immune responses and 2) the immune elements generated must have unfettered access to the tumor and be able to express their entire range of effector functions at the tumor site. The unique immunologic and anatomic features of the eye prevent the induction and expression of conventional immunity--a phenomenon known as 'immune privilege'. Although ocular immune privilege represents a theoretical obstacle to immune surveillance, some highly immunogenic intraocular tumors can circumvent immune privilege and undergo immune rejection. Uveal melanoma is the most common intraocular malignancy in adults, yet it occurs with a frequency that is no higher than neoplasms arising in conventional bodies. The presence of either tumor-infiltrating lymphocytes (TIL) or tumor-infiltrating macrophages (TIM) is associated with poor prognosis in uveal melanoma patients and suggests that some immune responses to intraocular tumors might exacerbate, rather than mitigate, tumor progression. Although counterintuitive, this proposition is consistent with the 'immune stimulation' hypothesis of tumor progression offered by Richmond Prehn over thirty years ago. It remains to be ascertained if immune stimulation affects the malignancy of ocular tumors, but it represents an intriguing explanation for the paradoxes of uveal melanoma.     

Choroidal biopsies for intraocular tumors of indeterminate origin

PURPOSE: To evaluate the role of pars plana vitrectomy-assisted incisional biopsies in the management of choroidal tumors of unclear origin. DESIGN: Retrospective, noncomparative, consecutive interventional case series. METHODS: Ten consecutive patients with indeterminate choroidal tumors underwent a standardized three-port pars-plana vitrectomy-assisted subretinal biopsy using a bimanual approach with standard intraocular forceps and a diamond knife. Specimens were fixed in formaldehyde embedded in paraffin and further subjected to histopathological and immunohistochemical analyses. RESULTS: A histologic diagnosis was obtained in all (10 of 10) cases including choroidal melanoma (five of 10), metastasis (two of 10), subretinal hemorrhage (two of 10), and nodular scleritis (one of 10). Five eyes were enucleated as a result of the histologic diagnosis. Three cases of postoperative complications were seen in three patients (newly formed rhegmatogenous retinal detachment, increased serous retinal detachment, and vitreous hemorrhage). No cases of intra- or extraocular tumor spread were detected through follow-up periods ranging from 3 to 29 months. CONCLUSIONS: Pars plana vitrectomy-assisted incisional biopsy is a valuable diagnostic procedure for cases of choroidal tumors of unknown origin in selected patients. However, the relatively high frequency of postoperative complications noted in the present study and the potential risk of dissemination of tumor cells underscores the importance of rigorous case selection.     

Review of optical coherence tomography for intraocular tumors

PURPOSE OF REVIEW: Optical coherence tomography has assumed an important role in the management of numerous ocular conditions. With regard to ocular oncology, optical coherence tomography can illustrate retinal changes overlying choroidal tumors. Some of these features include photoreceptor loss, intraretinal edema, and retinal thinning overlying choroidal nevus; fresh subretinal fluid with preservation of photoreceptors overlying choroidal melanoma; and intraretinal edema, retinoschisis, and retinal thinning overlying irradiated choroidal melanoma. RECENT FINDINGS: The optical coherence tomography features of tumors of the retinal pigment epithelium include typical findings of peaked vitreoretinal traction and retinal disorganization with combined hamartoma of the retina and retinal pigment epithelium, full-thickness retinal shadowing with congenital simple hamartoma, and photoreceptor loss and retinal thinning overlying congenital hypertrophy of the retinal pigment epithelium. SUMMARY: Optical coherence tomography of retinal tumors, such as retinoblastoma and astrocytic hamartoma, reveals full-thickness replacement of the retinal anatomic layers with the tumor and shadowing corresponding to the intralesional calcification. For all intraocular tumors, optical coherence tomography provides valuable information regarding the status of the retina and the retinal pigment epithelium and can be useful in ascertaining reasons for visual loss.     

A model for acoustic characterization of intraocular tumors

Human intraocular tumors and tumors derived from human tumor cell lines grown subcutaneously in the athymic nude mouse were scanned by diagnostic ultrasound. Radiofrequency scan data were converted to digital form and analyzed in the frequency domain. Characteristics of normalized power spectra were found to be significantly different among human spindle cell malignant melanomas, mixed/epithelioid malignant melanomas, metastatic carcinomas, and hemangiomas. Significant differences, as well, were found between implanted primary skin malignant melanomas and adenocarcinomas of the lung, colon, and stomach. Comparison of spectral properties of human intraocular and implanted tumors revealed that human spindle cell malignant melanomas and implanted melanomas exhibit similar characteristics. Human intraocular metastatic tumors from the lung were found to exhibit characteristics similar to those of implanted lung tumors. These results indicate that the implantation of human tumor cell lines in the nude mouse may provide a very useful model for application of diagnostic and therapeutic ultrasound modalities to human intraocular tumors.     

Biopsy in indeterminate intraocular tumors

OBJECTIVE: To describe an intraocular biopsy technique that allows accurate histopathologic diagnosis in cases of clinically unclassifiable uveal tumors. DESIGN: Retrospective noncomparative consecutive interventional case series. PARTICIPANTS/METHODS: Intraocular biopsies were performed by a vitreous cutter either by a two-port clear cornea approach in 11 patients with unclassifiable iris tumors or by a three-port pars plana vitrectomy in 23 patients with unclassifiable choroidal tumors. Specimens were formalin fixed and paraffin processed. Hematoxylin-eosin and periodic acid-Schiff stains were performed in all cases, with additional immunohistochemical stains using the alkaline phosphatase, antialkaline phosphatase method in cases that could not be conventionally classified. MAIN OUTCOME MEASURES: Clinical observation and histopathologic examination of intraocular biopsies. RESULTS: In 97% of cases (n = 33) a definite diagnosis could be established by the biopsy specimen. A melanoma could be diagnosed in 73% of cases (n = 8) of iris tumors and in 57% of cases (n = 13) of posterior intraocular tumors. Other diagnoses included nevus, metastasis, vasoproliferative tumor, hemorrhage, gliosis, and scleritis. Complications were encountered in four cases: a vitreous hemorrhage occurred twice, an inconclusive biopsy result, and an intraocular tumor spread occurred once, respectively. No increased tumor-related mortality was observed after a mean follow-up of 44 months. CONCLUSIONS: Intraocular biopsy by a vitreous cutter allows the histopathologic examination of formalin-fixed paraffin-embedded tumor tissue. This increases the diagnostic accuracy, avoiding the risk of extraocular tumor spread seen with transscleral biopsy techniques.     

Treatment of intraocular metastatic tumors

PURPOSE: Analysis of the clinical picture of intraocular metastatic tumors and the results of the treatment with various methods. MATERIAL AND METHODS: Between 1994-1997 intraocular metastatic tumors were diagnosed in 14 patients (19 eyes). There were 13 females and 1 male, aged 28 to 69 years (average 50). The primary tumor in 8 patients developed in the breast, in 4 cases in the lungs, 1 in the brain, and 1 in the kidney. In all patients the primary tumor was excised, then chemotherapy was applied in 9 cases, radiotherapy in 3 cases, and hormonal treatment in 2 cases. In 7 patients the metastatic process concerned also other organs: bones, liver, lungs, hypophysis, and lymphatic glands. Metastases developed in 10 months to 11 years since the diagnosis and treatment of the primary tumor. Intraocular tumors were the most often located near the optic disc (8 cases), or near the macula (4 cases). There were usually flat tumors (in 12 cases < 5 mm in thickness), creamy white, sometimes with pigment clamping. In order, to confirm the diagnosis of the tumor, USG was always performed and in 8 cases fluorescein angiography. In all cases topical treatment was applied, which consisted of irradiation with ruthenium (106Ru) in 6 eyes (in 1 case two times), laser coagulation in 3 eyes, and thermotherapy (TTT) with diode laser in 4 eyes, combined treatment (106Ru + TTT) in 2 eyes, 106Ru and 125I brachytherapy in one eye. The dose of radiation for the apex of the tumor was 60-90 Gy (av. 65). The eyeball was enucleated in 3 patients, 4 patients received chemotherapy. 2 patients received hormonal therapy, applied together with the topical treatment. RESULTS: In the majority of cases (14 eyes), a flat scar or the significant decrease of the volume of the tumor was obtained. 8 patients died, two are currently observed, the remaining 4 do not come to the control examination, and there is no information as to their fate. CONCLUSIONS: Good results of the treatment encourage further application of brachy and thermotherapy in the treatment of intraocular metastatic tumors. It allows for the conservative treatment of the eyeball, and also useful visual acuity is retained often.     

Genetics of primary intraocular tumors

Primary intraocular neoplasms are tumors that originate within the eye. The most common malignant primary intraocular tumor in adults is uveal melanoma and the second is primary intraocular lymphoma or vitreoretinal (intraocular) lymphoma. The most common malignant intraocular tumor in children is retinoblastoma. Genetics plays a vital role in the diagnosis and detection of ocular tumors. In uveal melanoma, monosomy 3 is the most common genetic alteration and somatic mutations of BAP1, a tumor suppressor gene, have been reported in nearly 50% of primary uveal melanomas. The retinoblastoma gene RB1 is the prototype tumor suppressor gene-mutations in RB1 alleles lead to inactivated RB protein and the development of retinoblastoma. Immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement is observed in B-cell or T-cell primary vitreoretinal lymphoma, respectively. Other factors related to the genetics of these three common malignancies in the eye are discussed and reviewed.