[Interferon alpha 2b for treatment of conjunctival melanoma: a case report]. / Interferon-α2b zur Therapie des Bindehautmelanoms : Ein Fallbeispiel.

A 71-year-old female patient with a status following multiple conjunctival excisions, histopathologically confirmed conjunctival melanoma (CMM) and also multiple therapy with mitomycin C presented with progressive conjunctival pigmentation. Treatment was carried out with local interferon α2b administration four or five times daily for several months. The lesion showed regression and lost pigmentation without any side effects.

[Inflammatory juvenile conjunctival nevus (IJCN)]. / Inflammatorischer juveniler Bindehautnävus (IJCN).

BACKGROUND: Pathologists may occasionally have difficulties in reliably assessing the dignity of tumour cells in histological sections, especially in nevi with junctional activity. PATIENT HISTORY: This case history of a boy suffering from an inflammatory juvenile conjunctival nevus (IJCN) is reported with a follow-up period of 25 years. Seven years after first surgical treatment of a histologically proven nevus, a recurrent pigmented lesion within the former operation area aroused the suspicion of it being a malignant melanoma. Logically, a second excision was performed followed by cryotherapy with liquid nitrogen (spray freezing). The histological diagnosis performed by a pathologist resulted in a malignant melanoma. A second recurrent pigmented conjunctival tumour developed fourteen years later. This lesion again aroused another strong clinical suspicion of malignant transformation into a melanoma. However, the histological examination of the biopsy at this time only showed benign nevus cells and areas of conjunctival melanosis without atypia. DISCUSSION: Especially in young patients, IJCN must be regarded as an independent type of nevus, which might lead even experts in ophthalmic pathology to over-diagnose this lesion as a malignant melanoma. This could mean that the wrong therapeutic steps were taken with surgical procedures that cause unnecessary mutilation. A reappraisal of the former histological specimens of the first recurrent tumour by other pathologists came to the conclusion that the initial diagnosis of melanoma could not be maintained. Nevertheless, we also strongly recommend follow-up examinations at regular intervals in cases of IJCN since we are aware of the fact that melanocytic tumours of the conjunctiva behave unpredictably.

Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study.

AIM: To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 microm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS: The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life.

[Intraocular involvement as initial symptoms of non-Hodgkin lymphoma]. / Intraokulare Beteiligung als erste Symptome eines Non-Hodgkin-Lymphoms.

BACKGROUND: The diagnosis of a intraocular lymphoma is often delayed because of a symptomatic pseudouveitis. CASE REPORT: We report on a 68-year-old female patient, who was referred because of a tumor of the optic disk in her right eye and bilateral uveitis with secondary glaucoma. The painful blind right eye was enucleated. The assumed diagnosis of a pseudouveitis as an initial manifestation of a B-cell lymphoma was confirmed histologically. She developed systemic extension and recurrence in the second eye despite polychemotherapy. The patient died from complications of her systemic tumor disease 15 months after initial symptoms. CONCLUSIONS: An initially unilateral and later bilateral uveitis in elderly patients which does not respond to steroid therapy could also be suspicious for an intraocular lymphoma. If the conjunctiva is not involved, the confirmation of the diagnosis requires a diagnostic viteous biopsy.

Long-term follow-up of Ru-106/Rh-106 brachytherapy for posterior uveal melanoma.

BACKGROUND: Currently available information about survival, local tumor control rates, secondary enucleation rates, and visual acuity following Ru-106/Rh-106 applicator therapy for choroidal and ciliochoroidal melanomas is limited in terms of duration of follow-up among surviving patients. METHODS: The authors performed a retrospective descriptive study of the rates of survival, local treatment failure, secondary enucleation, and visual acuity decrease in 140 patients (141 eyes) with choroidal or ciliochoroidal melanoma treated by Ru-106/Rh-106 applicator radiotherapy between 1964 and 1976. Median follow-up duration among surviving patients in this series was 17.3 years (mean 18.6 years). The Kaplan-Meier method was used to estimate cumulative survival rates and event rate curves. Multivariate Cox proportional hazards modeling was used to identify prognostic clinical variables associated with the various evaluated outcomes. RESULTS: The 15-year survival rate based on all causes of death was 48.0% (standard error=4.4%), and that based on confirmed and suspected metastatic uveal melanoma was 66.7% (standard error=4.5%). The cumulative 15-year rates of local treatment failure and secondary enucleation were 36.8% (standard error=4.4%) and 34.4% (standard error=4.5%) respectively. The cumulative 10-year rates of visual acuity loss to less than 20/200 and no light perception were 62.8% (standard error=4.4%) and 40.6% (standard error=5.2%) respectively. Prognostic factors associated with death from confirmed and suspected metastatic melanoma were greater tumor diameter and anterior tumor location. Greater tumor diameter was associated with local treatment failure. Baseline visual acuity equal to or worse than 20/200 was associated with profound visual acuity loss. CONCLUSIONS: Although a high proportion of treated eyes eventually lost a great deal of vision, and although many treated eyes ultimately underwent secondary enucleation, a substantial number of patients treated by plaque radiotherapy in this series survived for well over 10 years and retained the tumor-containing eye with a visual decrease of varying severity.

[Intraocular invasion of melanoma of the conjunctiva]. / Intraokulare Ausbreitung eines Melanoms der Bindehaut.

BACKGROUND: The treatment of a localised conjunctival melanoma usually requires local excision combined with cryotherapy, brachytherapy and/or local chemotherapy. CASE REPORT: A 71 year old woman suffering from a conjunctival melanoma located at the limbus of her left eye was treated by local excision and cryotherapy. After this therapeutic procedure two recurrences occurred which had been again treated by excision and cryotherapy and finally brachytherapy. Nevertheless, a third recurrent tumor developed and was treated again with deep lamellar sclerectomy and keratectomy. During this procedure the anterior chamber was opened inadvertently in a tiny spot. Some months later an intraocular invasion of the melanoma was diagnosed clinically and the eye had to be enucleated 5 years after the first treatment. Histological examination revealed extended melanoma growth into iris, ciliary body, anterior choroid, and tumor cell seedings in the antertior chamber. CONCLUSIONS: Removing a conjunctival melanoma especially such a tumor growing at the limbus, the surgeon has to pay attention not to open the anterior chamber during sclerectomy and keratectomy. The possibility that prior local surgical excision aided the intraocular extension is discussed.

[Mitomycin C in treatment of conjunctival melanoma and primary acquired melanosis]. / Mitomycin C bei der Behandlung von Bindehautmelanomen und primär erworbenen Melanosen.

BACKGROUND: Since 1995 we have used Mitomycin C additionally in the treatment of conjunctival melanoma and primary acquired melanosis. METHODS: We report on the therapy results of 14 patients suffering from pigmented conjunctival lesions (malignant melanoma 9 and primary acquired melanosis 5). After local excision, cryotherapy or irradiation all patients received one eye drop Mitomycin C (0.02%) four times daily for four to six weeks. RESULTS: We observed regression of the pigmentations in 11 cases after median follow up of 13.1 months. In one patient there was no change. Two cases showed progression with tumefaction. There were no adverse reactions except conjunctival hyperemia during therapy. CONCLUSIONS: Topical administration of Mitomycin C may be useful in the treatment of pigmented conjunctival lesions. Longer follow-up periods are necessary.

[Clinicopathologic study of 817 enucleations]. / Klinisch-pathologische Studie an 817 Enukleationen.

METHODS: The clinical findings, the indications for enucleation and the histopathological diagnoses from 817 eyes from the University Eye Hospital in Leipzig, enucleated between 01/01/1980 and 31/12/1989 (433 males; 384 females), were analysed retrospectively to investigate, however, the therapeutic and diagnostic importance of enucleation to ophthalmological problems. RESULTS: The most frequent underlying ocular diseases were: intraocular tumour (47.7%), surgical disease [primary glaucoma, retinal detachment, cataract] (18.6%), trauma [enucleation within 4 weeks after the event] (10.3%), systemic disease (6.6%), inflammation (6.1%), other diseases (10.7%). The final causes for enucleation were: intraocular tumour (46.4%), secondary glaucoma (31.6%), atrophia and phthisis bulbi (11.9%), inflammation (6.5%), trauma (0.9%), other diseases (2.7%). An increase in the enucleation rate was noted with increasing age. The ophthalmoscopic diagnoses of 8 i.o. malignant melanomas and 7 cases of retinoblastoma were histopathologically not verified. The histopathological diagnoses included: exudative-hemorrhagic lesion (7), metastasis (1) respectively M. Coats (3), retinal detachment (2), M. Norrie (1), panophthalmitis (1). In 2 cases of i.o. malignant melanoma and 2 cases of retinoblastoma the tumours were clinically unsuspected. The incorrect clinical diagnoses included: secondary glaucoma (2) respectively M. Coats (1), secondary glaucoma (1).

[Morphologic changes in the lens epithelium in patients with age-induced cataract, radiation and steroid cataract and cataract following eye contusion]. / Morphologische Veränderungen des Linsenepithels bei Patienten mit altersbedingter Katarakt, Strahlen- und Steroidkatarakt und Katarakt nach Contusio bulbi.

The lens epithelium of the human eye plays a crucial role in the pathogenesis of primary and secondary cataract. Sixty hematoxylin-eosinstained lens epithelia were examined using a light microscope. Cell parameters were compared to one another in the various age groups of patients, between patients with secondary cataract (radiation cataract, steroid cataract and traumatic cataract) and patients with senile cataract, and between male and female patients. The t-test was used for statistical comparison. The median cell density was 3116.5 cells/mm2. The median nucleus-plasma ratio was 1:2.74. Patients with secondary cataract had a larger medium cell and nucleus area as well as a higher nucleus-plasma ratio and a lower cell density than patients with senile cataract. A part from degenerative and proliferative cell changes we found various cell types. The age of patients and the cause of cataract correlate with morphometric changes of lens epithelium cells. However, there was no correlation between specific cytologic changes and causes of cataract.

[Metastasis of differentiated follicular thyroid carcinoma to the ciliary body]. / Metastase eines differenzierten follikulären Schilddrüsenkarzinoms in den Ziliarkörper.

A girl aged 20 years was suffering from a slowly growing tumor of the ciliary body of her left eye. The tumor was excised with iridocyclectomy supposed to be a melanoma. The histologic examination showed a well-differentiated follicular carcinoma of the thyroid gland. The primary tumor had been excised 16 years before, the diagnosis at that time was benign thyroid adenoma. After the successful removal of the ciliary body a follicular carcinoma of the thyroid gland was finally diagnosed and treated by total thyroidectomy and systemic 131I therapy.

Radiation effects on the optic nerve observed after brachytherapy of choroidal melanomas with 106Ru/106Rh plaques.

From 1966 to 1990 a total of 93 juxtapapillary choroidal melanomas were treated using 106Ru/106Rh plaques with a notch for the optic nerve. The choroidal melanoma was controlled after brachytherapy in 79 cases (85%). Fourteen eyes (15%) had to be enucleated because of tumor regrowth. Eye and optic nerve phantoms were fabricated, loaded with small-volume thermoluminescent dosimeters, treated with active plaques, and the radiation dose determined at the optic disc and along the optic nerve. The median dose within the anterior optic nerve was 51.2 Gy (range 10.3-60.5 Gy). The probability of developing complete radiation optic neuropathy (RON) was 23% and 53% at 5 and 10 years, respectively. The probability of developing partial RON was 66% at 5 years and 82% at 10 years. The probability of retaining visual acuity better than 0.5 was 38% at 5 years and 26% at 10 years. No dose-response relationship could be established from the ophthalmological, morphological and functional findings. Eyes following plaque irradiation with 50 Gy or more in the center of the optic nerve experienced significant radiation optic neuropathy, other eyes did not.

[Spontaneous growth inhibition in retinoblastoma]. / Spontane Wachstumshemmung beim Retinoblastom.

Report on 8 cases with spontaneous arrest of retinoblastoma. The incidence was 3.2% which is approximately 1000 times more than in other malignant tumors. Multifocal lesions suggesting that this form of "regression" may not be a regression at all. Spontaneous arrest of retinoblastoma is obviously a lesion of low malignant potential. The presence of a spontaneous arrest of retinoblastoma necessitates genetic counselling and examinations of the eyes in the offspring. Synonymous names are: 1. Spontane Rückbildung eines Retinoblastoms (spontaneous regression of retinoblastoma), 2. Retinoma, 3. Retinocytoma, 4. benign variant of retinoblastoma, 5. spontaneous arrest of retinoblastoma, 6. spontaneous cure of retinoblastoma.

[Results of treatment in malignant epithelial conjunctival tumors]. / Ergebnisse der Behandlung von malignen epithelialen Bindehauttumoren.

Tumors of the conjunctiva are rare, especially malignant epithelial tumors. Although these tumors grow very slowly and only exceptionally with local invasion, intensive treatment is necessary. We studied the results of combined treatment with excision and brachytherapy with strontium-90 in 30 patients with carcinoma in situ and squamous cell carcinoma. After a follow-up between 3 months and 8 years (average 3 years) only one patient suffering from a squamous cell carcinoma developed a recurrence after 1 year. Two patients with squamous cell carcinoma developed telangiectasis, one patient developed glaucoma, and one patient developed a scleral ulcer.

[Static and dynamic infrared thermometry and thermography in malignant melanoma of the uvea and conjunctiva]. / Statische und dynamische Infrarotthermometrie und -thermographie beim malignen Melanom der Uvea und Konjunktiva.

BACKGROUND: Thermometry and -graphy prove asymmetries of the circulation. Contact-free thermometry of the cornea is applied to find out whether this method can contribute to differential diagnosis of ocular melanomas. MATERIALS AND METHODS: Under standardized conditions the temperature of the cornea was measured in 30 patients with malignant melanoma of the choroid and the conjunctiva and 35 healthy subjects. The instruments were a handpyrometer (HPM, Messgerätewerk, Magdeburg) and the thermovision camera of AGA Infrared System, Sweden, with dynamic recording in colour. RESULTS: In healthy subjects there are no significant asymmetries in temperature under standardized conditions. The temperature of the cornea is elevated in both malignant melanomas of the choroid and the conjunctiva. CONCLUSIONS: Thermometry and -graphy of the cornea can contribute to the differentiation of malignant ocular melanomas from other ophthalmological diseases. They are also suited in long term observation of the course of the melanomas.

[Effect of histological criteria (TpNM classification, degree of differentiation) on mortality of patients with retinoblastoma]. / Der Einfluss histologischer Kriterien (TpNM-Klassifikation, Differenzierungsgrad) auf die Letalität von Patienten mit Retinoblastom.

153 patients suffering from retinoblastoma and treated between 1960 and 1980 were analysed retrospectively. Median follow-up was 11.2 years. 13 patients (8.5%) died from retinoblastoma. 3 patients died from a secondary osteosarcoma. The survival rates from patients with differentiated retinoblastomas did not differ from those with undifferentiated tumor cells. Optic nerve invasion decreased significantly the survival rate and involvement of the sectional line led to a survival rate after 5 years of only 22.2%. Due to 3 cases of death from secondary osteosarcoma, the survival rate of 91.14% after 5 years deteriorated to 87.64% after 10 to 14 years.