D. De Wolff-Rouendaal

Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma.

We studied the destructive effect of hyperthermia at sub-photocoagulation level of 45–60 °C on melanomas. Optimal conditions for spreading of heat into tissue are a wavelength of 700–900 nm, a temperature of 45–60 °C, an exposure time of 1 minute or more, and a beam diameter of several millimeters. In hamsters with subcutaneous melanomas we obtained a tumour necrosis of 6 mm depth at 60 °C and one minute exposure time. We performed transpupillary thermotherapy (TTT) with a diode laser at 810 nm in patients with choroidal melanomas prior to enucleation. Treatment is based on the fortunate situation that irradiation at this wavelength combines optimal tissue penetration with a low absorption by clear ocular media of 5% or less. In 3 TTT-treated eyes histopathology showed a depth of necrosis of 0.9, 3.4, and 3.9 mm. TTT may become a new useful treatment modality for choroidal melanoma but its ultimate value has yet to be assessed.

Topical application of 5-Fluorouracil in premalignant lesions of cornea, conjunctiva and eyelid

Local application of 5-Fluorouracil was practised on 5 patients. In 3 patients with multiple premalignant oculo-cutaneous lesions, two of whom had also premalignant epibulbar lesions, local 5% 5-Fu cream and/or 1% 5-Fu eyedrops were applied. In 2 other patients who had only premalignant lesions on the cornea and conjunctiva, 1% 5-Fu eyedrops were used only. In animal experiments 1% 5-Fu was not found to cause any damage to normal corneal and conjunctival epithelium. The frequency of the applications and the duration of the treatment were dependent on the location and extent of the lesions. Except for easily treatable lesions, caused by the separation of the tumour epithelium, no complications of local 5-Fu treatment were seen. The visual acuity improved in all 4 patients in whom the cornea was affected. In these premalignant conditions the diagnosis and assessment of the therapy were based on exfoliative cytology and biopsies.

Immunophenotypic markers to differentiate between benign and malignant melanocytic lesions

Background/aims: The authors investigated the expression of S100A1, S100A6, S100B, MelanA, and CEA in conjunctival naevi, primary acquired melanosis (PAM), conjunctival melanoma, and uveal melanoma in order to assess their potential usefulness in the pathological differential diagnosis of these entities. Methods: Paraffin embedded sections of 18 conjunctival naevi, 14 PAM, 16 conjunctival melanomas, and 20 uveal melanomas were immunostained for S100A1, S100A6, S100B, MelanA, and CEA, and expression was scored semiquantitatively. Results: Expression of S100A1 differed significantly between conjunctival naevi and conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%, respectively. Conjunctival melanomas had high average scores for S100A1 and S100B (71.4%, 62.9%, respectively), while uveal melanomas also had high S100A1 but low S100B scores (88.5%, 18.5%, respectively). MelanA was highly variable; naevi and uveal melanoma had higher average scores than conjunctival melanoma. CEA was hardly detectable in all four groups. Conclusion: S100A1 seems to be a possible candidate to differentiate conjunctival naevi from conjunctival melanoma. S100B seems to differentiate between uveal melanoma and conjunctival melanoma. However, the study size was small and therefore the data have to be confirmed by others.

Optic glioma with intraocular tumor and seeding in a child with neurofibromatosis

We treated a 3-year-old boy with neurofibromatosis who had an optic glioma, intraocular extension with seeding, and iris tumors. On the basis of results of ultrasonography, computed tomography, magnetic resonance imaging, and fine needle aspiration, other intraocular and orbital tumors were excluded. Because of the malignant intraocular aspect, the optic nerve glioma was extirpated. Histologic examination confirmed the diagnosis of an optic nerve glioma with intraocular extension, seeding, and iris nodules. In this juvenile pilocytic astrocytoma with secondary perineural fibrous hyperplasia, several mitoses were found in the orbital and intraocular parts. In the optic canal, three small islands were found that were compatible with the diagnosis of malignant astrocytoma, grade 3. The iris nevi appeared as iris pits and not like the Lisch nodules typical of neurofibromatosis. Café au lait spots were present on the skin. The family history was positive for neurofibromatosis. The results of this study demonstrate that optic gliomas are true astrocytomas and not hamartomas, and have a continuous scale from benign to malignant differentiation.

Hematoporphyrin derivative photoradiation treatment of experimental malignant melanoma in the anterior chamber of the rabbit

The effects of Hematoporphyrin Derivative Photoradiation Therapy (HpD-PRT) on Greenes amelanotic melanoma implanted into the anterior chamber of rabbits have been examined by biomicroscopy, fluorescein angiography and histopathology. The tumors were irradiated 24 hours after injection of HpD when both the porphyrin concentration and the porphyrin ratio tumor/iris were highest. Blanching and shrinkage of tumors were the first signs of tumor destruction. Fluorescein angiography as soon as 20 minutes after irradiation found non-perfusion of blood vessels at the tumor surface. Histopathological observation of vessel wall destruction is in agreement with this finding. Subtotal tumor necrosis was demonstrated in 12 out of 13 experiments. Necrosis was complete in only one experiment. Clusters of viable tumor cells were found when shielded behind pigment, at the tumor periphery and around some blood vessels. Lens damage was observed after irradiation when the iris pigment epithelium was disorganized by the tumor. The iris contained high concentrations of porphyrin and PRT resulted in depigmentation, non-perfusion of the capillary bed, damage to larger iris vessels and finally atrophy. Light intensity measurements were performed in vivo during PRT. The average effective attenuation coefficient at 630 nm was 0.56 mm-1 at the beginning of irradiation and 0.87 nm-1 at the end. Results indicate that as a treatment HpD-PRT in itself might be insufficient but may prove to be an effective modality in combination with other tumor destructive therapies.

Heterogeneous expression of melanoma-associated antigens in uveal melanomas

Twenty-five uveal melanomas were stained with seven monoclonal antibodies (MoAbs) recognizing different antigens on cutaneous melanomas. A two step immuno-peroxidase procedure was used. Phenotypic heterogeneity was observed for four MoAbs (M.2.2.4, AMF-7, 225.28S, PAL-M1) while two MoAbs (NKI-beteb, CL203.4) reacted strongly with most (85%) uveal melanomas, and one MoAb (R-24) showed very low reactivity. Despite heterogeneity, co-expression of some antigens was observed. Expression of the antigen recognized by MoAb M.2.2.4. was significantly lowered by pre-enucleation irradiation while the other antigens remained unchanged. Expression of antigens on uveal melanomas differed markedly from primary cutaneous melanomas. The clinical relevance of these findings awaits further study.

Echographic differentiation of histological types of intraocular melanoma

The aim of this study was to assess the differentiation of histologically different types of choroidal melanomas by means of clinical and quantitative acoustic/texture parameters of echograms. Clinical parameters were graded by morphological, kinetic and quantitative statements about the A- and B-mode echograms by a skilled diagnostician. Acoustic/texture parameters were obtained by processing and analysing radio frequency, AM-demodulated and FM-demodulated echograms. The data were preprocessed to remove influences induced by beam diffraction and focusing. The correlations between the clinical parameters were lower than 0.5 but significant in a few cases. The best set of four clinical echographic parameters enabled a retrospective classification of spindle type melanomas vs. mixed + epithelioid type melanomas with an accuracy of 77% (area under the ROC-curve of 86%). These figures do not enable, however, a prospective diagnosis. The correlations of the clinical parameters with the acoustic/texture parameters were investigated. The mutual correlations between the latter parameters were also assessed, the most significant (0.70) being between the speckle size and the slope of the linearized backscattering spectrum. The discriminant analysis performed with the best four acoustic/texture parameters (n = 30) yielded a sensitivity of 89%, a specificity of 92% and an area under the ROC-curve corresponding to a probability of correct classification of 96.6%. When using these data prospectively to classify tumours of unknown cell type (n = 21), this classification could be performed in 86% of cases.

Conjunctival melanomas in The Netherlands: a follow-up study

In a follow-up study of 45 conjunctival melanoma patients the recurrence rate after local excision was 80% but the mortality rate due to metastasis was low, only 2 out of 25 cases in which the recurrences could be controlled by repeated local excisions. In the 18 cases in which exenteration was required, because of the unfavourable localization of the melanoma or repeated recurrences, the mortality rate due to metastatic disease (7 out of 18) was high.

Nuclear Magnetic Resonance Imaging of Intraocular Tumors

Of 11 patients with intraocular tumors who underwent magnetic resonance imaging, seven had melanoma and one each had lymphoma, metastatic carcinoma, hemangioma, and hemorrhage. All were localized in the choroid. We compared the results of the magnetic resonance imaging examinations with those of ophthalmic ultrasonography, external inspection, and histopathologic studies. Magnetic resonance imaging detected six of the seven choroidal melanomas. Demarcation between the tumor and the sclera was excellent. Extrascleral tumor extension could be excluded. Hemorrhage in and beside the choroidal melanoma could be seen separately. Magnetic resonance imaging differentiates choroidal tumors from the surrounding intraocular and extraocular tissues better than computed tomography does, making it an important new diagnostic procedure.

Bilateral diffuse benign melanocytic tumours of the uveal tract

In a patient treated for gall-bladder carcinoma bilateral choroidal tumours were clinically interpreted as intraocular metastases. Post mortem histological examination of both eyes revealed a bilateral diffuse benign melanocytic tumour of the uveal tract. The association of bilateral uveal naevi with terminal carcinomas has been reported in seven other cases; it may be a new ophthalmological syndrome.