Posterior Uveal Melanoma Research Articles

Cytogenetic analysis of posterior uveal melanoma

Cytogenetic analysis was performed on short-term cultures of primary tumor samples from seven patients with posterior uveal melanoma. Informative data were obtained from four patients, all of whom had a near-diploid chromosomal number and clonal chromosomal alterations. Analysis of one patient's tumor revealed monosomy 3 as the only cytogenetically distinguishable aberration. Trisomies of chromosome 8 and i(8)(q10) were detected in two other patients in combination with monosomy of chromosome 3. The fourth patient's karyotype displayed two different translocations. One translocation, der(6)t(6;8)(q12;q13.1), resulted in the over-representation of 8q13.1→qter and a partial monosomy of 6q12→qter; the other translocation, der(9)t(6;9)(p12;p23), produced a partial trisomy of 6p12→pter and a partial monosomy of 9p23→pter. These results support the view that the recurring pattern of chromosomal rearrangements in ocular melanoma is unique from that associated with cutaneous malignant melanoma. Furthermore, these results help confirm that chromosomes 3, 6, and 8 are nonrandomly altered in ocular melanoma.

Approach to Counseling Patients with Posterior Uveal Melanoma

Approach to Counseling Patients with Posterior Uveal Melanoma

Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma.

We present ten cases of posterior uveal melanoma which were karyotyped after short-term culture. One tumour had a normal chromosome complement. The remaining nine tumours were cytogenetically abnormal, with chromosomes 3, 6, 8, 11, and 13 most frequently involved. Abnormalities of chromosome 13 were seen in two cases, chromosome 11 in three cases, and chromosomes 3, 6, and 8 in five cases. Four tumours, all derived from the ciliary body, demonstrated monosomy 3 and i(8q), confirming the involvement of these aberrations with a subgroup of uveal melanomas arising from the ciliary body.

Massive Orbital Extension of Posterior Uveal Melanomas

Among 2,135 consecutive patients with posterior uveal melanoma who were evaluated clinically in the Ocular Oncology Service of Wills Eye Hospital between February 1974 and December 1986, 123 (5.8%) were found to have some degree of extrascleral extension of the tumor. Ten of the 2,135 patients (0.5%) had massive orbital extension we defined as extrascleral tumor having an estimated volume exceeding 1,000 mm3. Three of these patients were characterized by orbital recurrence sometime after enucleation, whereas seven had massive orbital extension as the initial manifestation of the neoplasm with no prior history of enucleation. These cases of advanced orbital extension are presented in detail with emphasis on clinical features, diagnostic problems, pathologic findings, and follow-up observation. Based on our observations, suggestions are made regarding the diagnosis and management of advanced orbital extension of posterior uveal melanoma.

Uveal Melanoma and Pregnancy: A Report of 16 Cases

A review of 3706 consecutive patients with uveal melanoma over a 17-year period revealed that 16 patients (0.4%) were pregnant women at the time of diagnosis. The mean age at presentation in this group was 30 years and the mean months of gestation at the time of diagnosis of the posterior uveal melanoma was 6 months. Seven of the sixteen tumors were active uveal melanomas at the initial examination and were treated immediately, while the remaining nine tumors were initially diagnosed as suspicious choroidal nevi or dormant choroidal melanomas, seven of which grew into active melanomas during the course of the pregnancy, necessitating therapy. The tumors were managed by enucleation in 10 cases, plaque radiotherapy either during or after pregnancy in 4 cases, and observation in 2 cases. Histopathologically, the melanomas did not differ appreciably in cell type, mitotic activity, and other features when compared with a matched group of tumors in nonpregnant women. All of the patients who elected to carry the pregnancy to term (14 cases) delivered healthy babies with no placental or infant metastases. The 5year survival rate using the life table method in these pregnant women with posterior uveal melanoma is 71% and is similar to the survival of nonpregnant women with posterior uveal melanoma reported in other series.

Enucleation after Plague Radiotherapy for Posterior Uveal Melanoma: Histopathologic Findings

A review of 1019 patients with posterior uveal melanomas, who were treated with episcleral plaque radiotherapy between April 1976 and December 1987, showed that 59 (6%) of these patients have thus far required enucleation of the affected eye. The most common clinical reasons for enucleation were tumor regrowth (51 %) and neovascular glaucoma (31 %). These irradiated melanomas were of mixed cell type in 40 cases (68%), spindle in 10 cases (17%), totally necrotic in 7 cases (12%), and epithelioid in 2 cases (3%). Some degree of tumor necrosis was seen in all cases. Overall, the median number of mitoses per 40 high-power fields in these irradiated tumors was 0. Most (64%) of the tumors had no identifiable mitosis in 40 high-power fields. A three-way simultaneous comparison of the following groups was made: irradiated eyes enucleated for tumor regrowth, irradiated eyes enucleated for neovascular glaucoma, and a matched group of nonirradiated posterior uveal melanomas. This comparison showed that the largest tumor dimension was significantly greater in the irradiated eyes enucleated for tumor regrowth than in the other two groups. Mitotic activity was significantly higher in the irradiated tumor regrowth and nonirradiated groups than in the irradiated neovascular group. There was no significant difference among the three groups in an analysis of height. The results suggested that mitotic activity may exist after plaque radiotherapy, especially when there is clinical evidence of tumor regrowth.

Traumatic Enucleation for Posterior Uveal Melanoma

Two features of eyes enucleated for posterior uveal melanoma that may serve as indicators for traumatic enucleation and relate to dissemination of tumor cells at the time of enucleation are myelin artifact of the optic nerve head and acute hemorrhage within the tumor. Myelin artifact occurs when crushed optic nerve tissue is squeezed into the eye at the time of enucleation. Intralesional hemorrhage may occur during surgery and may be correlated with fluctuations in intraocular pressure. We reviewed 519 cases of posterior uveal melanoma treated by enucleation between 1950 and 1970. Without knowledge of the follow-up data, we examined histologic sections for myelin artifact, intralesional hemorrhage, subretinal hemorrhage, Callender cell type, size of tumor, necrosis, and scleral or orbital invasion. Neither myelin artifact nor intralesional hemorrhage were independent prognostic risk factors. These findings do not support or refute the hypothesis that excessive trauma during enucleation results in a worse prognosis.

A Randomized Study of Methanol-Extraction Residue of Bacille Calmette-Guerin as Postsurgical Adjuvant Therapy of Uveal Melanoma

A randomized controlled clinical trial of methanol-extracted residue of bacille Calmette-Guerin adjuvant treatment of posterior uveal melanoma was undertaken. Of 113 patients, 34 patients received adjuvant immunotherapy and 79 patients received no treatment. No difference in survival was observed between the adjuvant-treated group and the control group of patients. This study found that the size of the tumor was a highly significant risk factor for death caused by metastasis of uveal melanomas. The standard deviation of the nucleolar area of the neoplastic cells was a significant risk factor, even though patients with tumors composed of Callender's spindle-type cells were not included in the study.

Clinical prognostic factors in patients with posterior uveal malignant melanoma

The authors evaluated the prognostic value of clinically assessed variables for predicting length of survival until death from metastatic disease in 237 patient with a primary choroidal or ciliary body melanoma. Using multivariate Cox proportional hazards modeling, the authors identified the largest linear basal tumor diameter (mm), estimated by indirect ophthalmoscopy and fundus drawing, the location of the anterior margin of the tumor relative to the ocular equator and ora serrata, and the age of the patient at the time of treatment as the best combination of the clinically assessed variables for predicting survival. For each patient in this group, the authors computed a prognostic index based on the best multivariate Cox model. They showed that patients with low, intermediate, and high values of prognostic index had low, intermediate, and high melanoma-related mortality rates, respectively, during the first 5 to 8 posttreatment years. These results suggest that: (1) clinically assessed variables evaluated according to a standardized protocol are useful for predicting the survival of treated patients with posterior uveal melanoma and (2) ophthalmologists who assess potential clinical prognostic variables consistently may identify subgroups of patients with comparable mortality risk on the basis of noninvasive testing.

Cytogenetic findings in six posterior uveal melanomas: Involvement of chromosomes 3, 6, and 8

Six posterior uveal melanomas were karyotyped after short-term culture. One had a normal chromosome complement; the remaining five had limited chromosome changes. Involvement of chromosomes 1 and 6 was noted in two and four cases, respectively, and three ciliary body tumours demonstrated both monosomy 3 and i(8q).

Accuracy of Diagnosis of Choroidal Melanomas in the Collaborative Ocular Melanoma Study

In the 3-year period during which patients were enrolled into the Collaborative Ocular Melanoma Study, 413 eyes with clinical diagnoses of choroidal melanoma were examined histopathologically as of December 31, 1989. Four hundred eleven of these eyes were found to be diagnosed correctly. One eye, removed after preoperative external beam radiation, was found to have a hemangioma. The second eye, removed after radioactive iodine plaque placement, was described as a magnocellular nevus (melanocytoma) by four of the five pathologists on the Collaborative Ocular Melanoma Study Pathology Review Committee. The Collaborative Ocular Melanoma Study misdiagnosis rate of 0.48% is the lowest ever reported. The major challenge with regard to posterior uveal melanomas is no longer that of correct diagnosis but rather determination of the optimal treatment.

Reasons for Enucleation after Plaque Radiotherapy for Posterior Uveal Melanoma: Clinical Findings

A review of 1019 patients with posterior uveal melanomas who were treated with episcleral plaque radiotherapy showed that 59 (6%) required enucleation of the affected eye. Seventeen of the enucleations were done within 1 year, 30 within 2 years, and 55 within 5 years. The enucleated eyes had been treated with a cobalt-60 plaque in 39 cases, a ruthenium-106 plaque in 13 cases, an iodine-125 plaque in four cases, and an iridium-192 plaque in three cases. The primary reasons for enucleation included tumor regrowth in 30 cases (51 %), neovascular glaucoma in 18 (31 %), patient request in five (8%), sclera) melting in four (7%), painful bullous keratopathy in one (2%), and hemolytic glaucoma in one (2%). The time interval from plaque treatment to eventual enucleation averaged 29 months. Tumor regrowth requiring enucleation was detected clinically an average of 28 months after treatment. In these cases the average radiation dose to the tumor apex was 7700 cGy and to the tumor base 36,000 cGy. Uncontrollable neovascular glaucoma occurred an average of 38 months after plaque radiotherapy and, most commonly, after cobalt-60 plaques were used. Eyes with plaque-induced scleral melting eventually required enucleation after an average of 10 months. In all cases of sclera) melting, the tumor was ciliochoroidal.

Recurrence of Posterior Uveal Melanoma after 60Co Episcleral Plaque Therapy

The authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with 60Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (logrank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).

106Ru/106Rh plaque radiotherapy for malignant melanomas of the choroid. With follow-up results more than 5 years.

Therapeutic results are presented with follow-up examinations of at least 5 years (min. 5 years, max. 22 years) after 106Ru/106Rh plaque radiotherapy of posterior uveal melanomas. Out of 227 patients 146 (= 64.3%) could be treated successfully, 37 (= 16.3%) had to be enucleated and are alive, 44 (= 19.4%) died from metastases and 40 (17.6%) from other causes. 75.0% of all small melanomas (T1a) showed an excellent regression pattern to flat scars. Five years after treatment the survival rate was 83.7% (deaths from any causes) respectively 88.2% (deaths from metastases only) and 64.8% (deaths from any causes) respectively 79.7% (deaths from metastases only) ten years after irradiation. 106Ru/106Rh plaque radiotherapy can be recommended for small (T1a, b) and medium sized (T2) choroidal melanomas.

The Effect of Pre-enucleation Radiotherapy on Mitotic Activity of Choroidal and Ciliary Body Melanomas

The authors studied the mitotic activity of 21 choroidal and ciliary body melanomas treated by external beam radiotherapy (2000 rad in 5 fractions over 5–7 days) before enucleation and 21 case-by-case matched nonirradiated uveal melanomas. The Wilcoxon signed ranks test and McNemar's fourfold table test were used to compare the mitotic activity of the irradiated and nonirradiated tumors. The results of these analyses suggest that pre-enucleation external beam radiotherapy substantially reduces the mitotic activity of posterior uveal melanomas (P < 0.005). This information supports current efforts to mount a successful randomized clinical trial of pre-enucleation radiotherapy in high-risk patients with choroidal and ciliary body melanomas.

Regression of posterior uveal malignant melanomas after cobalt plaque radiotherapy.

We reviewed the records of 17 patients with posterior uveal malignant melanoma who had been followed for at least 3 months prior to cobalt plaque radiotherapy and whose tumor had been documented to enlarge in thickness during that interval. We evaluated the relationship between the rates of pretreatment tumor enlargement and post-treatment tumor shrinkage using linear regression analysis. We found that the rate of postirradiation tumor shrinkage correlated strongly with the rate of preirradiation tumor enlargement regardless of whether the pretreatment rate of growth was slow, intermediate or rapid. We speculate that the more rapidly regressing tumors were more mitotically active than their more slowly regressing counterparts. If true, the survival rate of patients whose posterior uveal malignant melanomas regress rapidly following radiation therapy may prove to be worse than that of patients whose tumors regress slowly.

The Mathematics of Melanoma Volume-Reply

In Reply. —If there were a reliable and practical direct method for measuring tumor volume, that method might well provide a prognostic indicator better than largest tumor diameter of posterior uveal melanomas. Unfortunately, there is no such method currently available. In our extensive clinical experience, choroidal and ciliary body melanomas commonly have very irregular shapes. Although the volume computation suggested by Dr O'Rourke would be quite appropriate for some of these tumors, it would be inappropriate for many others. Furthermore, we have (in our Cox modeling of potential risk factors) investigated numerous volume formulas, including the one Dr O'Rourke suggests, as well as more simple formulas such as the cubic volume computation commonly used. What we have found from those explorations is that largest tumor diameter still appears to be as good a predictor of mortality as any of the computed volumes based on maximal and minimal basal diameters and

Posterior Uveal Melanomas in Aphakic and Pseudophakic Eyes

Of 650 eyes with posterior uveal melanomas that were accessioned at the Armed Forces Institute of Pathology from 1975 to 1983, 28 were aphakic and eight were pseudophakic. In ten of these 36 cases, the cataract had been unilateral. Only two patients had been examined with preoperative A-scan ultrasonography to obtain the axial length of the eye. None of the patients had been examined for possible intraocular tumors by either A- or B-scan ultrasonography. We believe that in many of these cases the tumor was large enough to have been detected at the time of cataract surgery. Thus, if the lens is too opaque for the fundus to be viewed, B-scan ultrasonography should be used before cataract extraction.

Lymphocyte Subpopulations Before Therapy in Patients With Uveal Malignant Melanoma

T-cell and B-cell lymphocyte subpopulations, monocytes, granulocytes, and immunoglobulin receptors were measured with monoclonal antibodies and flow cytometric techniques in the peripheral blood of 266 patients with posterior uveal melanoma before therapy. Statistically significant differences were found in T-helper/inducer (OKT4), T-suppressor/cytotoxic (OKT8), and B-lymphocyte populations between patients with uveal melanoma and age-matched controls.

Hepatic Metastasis and Orbital Recurrence of Uveal Melanoma After 42 Years

A 70-year-old woman who had undergone enucleation of the left eye at the age of 28 years because of complications from an injury to the globe, and in whom a previously unsuspected posterior uveal melanoma was detected after enucleation, had no further problems until 42 years later, when she was discovered to have a liver malignancy of undetermined origin. After six months of chemotherapy, the patient developed a mass in the anophthalmic left orbit. Biopsy of the orbital mass disclosed malignant melanoma, and reexamination of the liver biopsy specimen disclosed similar malignant melanoma cells. The patient had no clinical evidence of a primary melanoma other than the one involving the eye. It is possible that the patient had subclinical melanoma cells in the liver for 40 years. However, another possibility is that the patient had residual melanoma cells in the orbit which eventually metastasized to the liver.