Metastases in the ophthalmic region in Denmark 1969-98. A histopathological study

PURPOSE: To evaluate the patterns of origin and anatomical localization of histologically verified metastases in the ophthalmic region in Denmark during 1969-98, and to compare the findings with those of a similar study for the period 1944-68. METHODS: All metastatic lesions presented at the Eye Pathology Institute, University of Copenhagen during the period 1968-98 were investigated. RESULTS: Metastases were found in 81 specimens from the eye and eye region in 76 patients (32 men, 44 women). Five patients had bilateral involvement. The most frequent site of involvement was the uvea (63%), followed by the orbit (26%) and the eyelids (10%). Breast cancer accounted for the most frequent primary tumour (38%), followed by lung cancer (24%) and skin melanoma (14%). CONCLUSION: The pattern of anatomical location of metastases in the ocular region has not changed since 1944. The incidence of metastases has fallen significantly throughout the period.     

Conjunctival melanoma and melanosis: a reappraisal of terminology,classification and staging

This paper aims to stimulate debate on the terminology, classification, grading and staging of conjunctival melanosis and melanoma. We audited our results with 76 invasive conjunctival melanomas. Staging according to the sixth edition of the Tumour Node Metastasis (TNM) system did not correlate well with tumour extent and outcome. Approximately 50% of invasive melanomas were associated with ‘primary acquired melanosis with atypia’, a term which in our opinion underestimates the gravity of this disease. We also found deficiencies in the grading, terminology and classification of conjunctival melanocytic abnormalities. In summary, we suggest that the term ‘primary acquired melanosis’ be reserved for clinical diagnosis. Histologically, this abnormality can be categorized more precisely as either ‘hypermelanosis’ or ‘conjunctival melanocytic intraepithelial neoplasia (C‐MIN)’. ‘Primary acquired melanosis without atypia’ can be termed more accurately as ‘C‐MIN without atypia’. In view of the high risk of invasive melanoma, we suggest that ‘primary acquired melanosis with atypia’ be termed ‘C‐MIN’ with atypia, with the more severe changes regarded as melanoma in situ. To improve objectivity in the reporting of C‐MIN, we propose a scoring system based on horizontal and vertical spread and degree of severity of melanocytic atypia. We suggest that the TNM staging system for conjunctival melanoma be revised to: (i) include a Tis stage; (ii) take account of tumour size, quadrant and caruncular involvement; and (iii) improve staging of any local invasion beyond conjunctiva.     

Metastasis of choroidal melanoma to the contralateral choroid, orbit, and eyelid.

A 52-year-old woman was found to have a small juxtapapillary pigmented lesion in the choroid of the left eye. This lesion remained clinically stationary for one year, but subsequent growth prompted enucleation of the eye. The tumour was diagnosed histologically as a choroidal malignant melanoma of mixed cell type. Approximately 52 months later the patient developed proptosis of the contralateral (right) eye. Orbital ultrasonography showed a large mass in the right orbit, which was confirmed by needle biopsy to be a melanoma. In addition the patient was found to have metastatic melanoma to the choroid, right lower eyelid area, and liver. The development of simultaneous orbital, choroidal, and eyelid metastases from a contralateral choroidal melanoma is of ophthalmic interest and appears to be unique.     

Cutaneous malignant melanoma metastatic to the eye, lids, and orbit

The incidence of malignant cutaneous melanoma is increasing faster than any other cancer. Thus, it will become an increasingly common source of metastatic disease to the eye, lids, and orbit. Herein, we have performed a systematic review of previously published cases including patient characteristics, clinical presentation, diagnostic techniques, current treatments, and outcomes. At the time of ocular diagnosis, nearly all reported patients had a known history of cutaneous melanoma and synchronous non-ocular metastases. Several aspects help in differentiating the tumors from primary uveal melanomas such as the presence of symptoms, rapidly growing multifocal tumors, vitreous seeding, and histopathological findings. Intraocular metastases (uvea, vitreous, retina, and anterior-segment) are more common and occur in younger patients than extraocular metastases (eyelids, orbit, and extraocular muscles). Palliative radiation therapy is often used for intraocular disease. Orbital metastases from cutaneous melanoma commonly involve the extraocular muscles resulting in diplopia and exophthalmos. The mainstays of extraocular treatment are surgical resection and radiation therapy. Unfortunately, there are few good options for systemic treatment of diffusely metastatic melanoma. Therefore, patients with ocular metastasis should be managed to prevent loss of vision or loss of the eye, and to maximize their quality of life.     

Parents with unilateral retinoblastoma: their affected children.

BACKGROUND: A retrospective analysis of all patients with retinoblastoma on file at the Ophthalmic Oncology Center of the New York Hospital, Cornell University Medical Center was performed to examine the characteristics of retinoblastoma in children with a unilaterally affected parent. METHODS: Data were analysed for laterality of disease, age at initial diagnosis, number of tumour foci at diagnosis, ocular outcome, and patient survival. RESULTS: There were 54 patients, including nine pairs of siblings, diagnosed with retinoblastoma, each of whom had one unilaterally affected parent. The retinoblastoma was bilateral in 49 (91%) patients and unilateral in the remaining five (9%). The mean age at diagnosis was 10.5 months (range 1-36 months) and 35 patients (65%) were diagnosed within the first year of life. The mean number of initial tumour foci was 1.7 per eye; 1.6 foci per eye in bilaterally affected patients, and 3.7 foci per eye in unilaterally affected patients (p = 0.36). Retention of the eye was possible for 51 of 103 eyes affected with retinoblastoma. The mean follow up for patients was 9.0 years, with a range of 1 month to 30.5 years. There were a total of 12 deaths (22%): from retinoblastoma (two), sarcoma (five), cutaneous malignant melanoma (one), cancer type unknown (two), and cause unknown (two). CONCLUSION: Overall, the characteristics of retinoblastoma patients with a unilaterally affected parent, were similar when compared with all retinoblastoma patients with a positive family history.     

Rapid improvement of radiation-induced neovascular glaucoma and exudative retinal detachment after a single intravitreal ranibizumab injection

Neovascular glaucoma is a serious complication arising from irradiation of uveal melanoma. Treatment options include panretinal photocoagulation, peripheral retina cryotherapy, photodynamic therapy with verteporfin, triamcinolone injections and surgical removal of the dying tumour mass. Nevertheless, enucleation of the affected eye often is inevitable. The authors describe a case report of a radiation-induced neovascular glaucoma and exudative retinal detachment caused by malignant melanoma of the uvea that was treated with intravitreal ranibizumab.     

Primary malignant tumours of eye and adnexa in Eastern Nepal

Background: The purpose of the present paper was to report the spectrum of primary malignant tumours of eye and adnexa at BP Koirala Institute of Health Sciences, Nepal, from 1995 to 2000. Methods: A retrospective study of medical records with histopathological confirmation of malignant tumours of the eye and adnexa was done for the years 1995?2000. A total of 116 consecutive medical records from the Department of Pathology at BP Koirala Institute of Health Sciences were retrieved. All those patients with primary ophthalmic malignancies were included and non‐malignant cases were excluded. Results: There were 80 patients of which 39 (48.8%) were male and 41 (51.2%) were female. Four patients had bilateral involvement. The most common malignancy was retinoblastoma (45.2%), followed by basal cell carcinoma (22.6%). Conclusion: Retinoblastoma is the most common eye cancer. The incidence of melanomas is correspondingly lower than that reported in the West. The present pilot study, the first of its kind, will lay the foundation for the monitoring of the future pattern of ophthalmic malignancies in Nepal and provide a basis for comparison elsewhere.     

Plasmacytoma of the uvea in a case of multiple myeloma

A case of plasmacytoma in the uvea, both clinically and grossly anatomically mimicking a malignant melanoma, is described in a 63-year-old man who died from multiple myeloma. This is an extremely rare condition in the eye. Only one report of a similar tumour has been found in the literature.     

Metastatic tumours to the conjunctiva: report of 10 cases.

AIMS/BACKGROUND: Ten patients with metastatic tumours to the conjunctiva and the clinical aspects of this rare form of ocular metastasis are described in this study. METHOD: All patients with ocular and adnexal metastatic tumours referred to an ocular oncology service were reviewed and those having conjunctival metastases were studied for the site of their primary tumour, clinical features, and treatment of the conjunctival tumour, associated ocular and systemic findings, and the patients' outcome. RESULTS: The primary malignancy was carcinoma of the breast in four, lung cancer in two, laryngeal carcinoma in one, cutaneous melanoma in two, and unknown in one patient. The conjunctival metastases appeared after the primary tumour over a mean period of 44 (8-130) months. They were solitary in eight cases, located in bulbar conjunctiva in six, palpebral conjunctiva in two, and in limbus and forniceal conjunctiva in one patient each. The tumour was yellow in colour in seven patients, red in two, and brown in one. Eight patients also had metastases to other ocular structures. Seven patients received external beam radiotherapy to the affected eye, two were managed by excisional biopsy, and one with chemotherapy. The mean survival after the diagnosis of conjunctival metastasis was nine (range 2-26) months. CONCLUSION: Metastatic tumours to the conjunctiva appear at an advanced stage of the systemic disease when there are other ocular and organ metastases. The presence of a conjunctival mass in a patient with a prior systemic cancer should alert the ophthalmologist to the possibility of a conjunctival metastasis and evaluation should be pursued.     

双眼异时性视网膜母细胞瘤21例临床分析

目的　通过分析双眼异时性视网膜母细胞瘤（RB）患儿的临床资料,确定高危因素,制订合理的随访计划,从而使肿瘤得以早期发现、早期治疗。方法　回顾性病例分析。收集2014年12月至2019年3月北京儿童医院收治的第一眼确诊为RB后,第二眼发现新发RB的病例共21例,分析双眼确诊间隔时间、发病年龄、首发症状,以及第二眼的确诊方法与肿瘤分期（IIRC）关系等。眼底检查以全身麻醉下间接眼底镜联合RetCam作为常规检查。结果　第一眼发病时患儿的年龄为1~36个月,平均12.2个月,13例年龄≤12个月;第二眼发病年龄为3~84个月,平均25.7个月,19例年龄≤36个月;双眼发病间隔时间为1~48个月,平均13.7个月。第二眼有首发症状者4例,17例（81.0%）在随诊例行检查时发现,无临床症状。第二眼肿瘤分期:A期8例,B期4例,C期1例,D期6例,E期2例。第二眼肿瘤以全身麻醉下间接眼底镜联合RetCam检查发现为主,患者多为早期。结论　第一眼RB发病年龄≤12个月是第二眼发生RB的高危因素,双眼确诊的间隔时间多≤ 36个月;定期、规律随诊和全身麻醉下间接眼底镜联合RetCam检查是早期发现第二眼RB的有效方法。     

A retrospective analysis of primary eye cancer at the University of Alabama at Birmingham 1958-1988. Part I: Eye and orbital cancer.

Records of 99 patients with 100 primary eye cancers seen at the University of Alabama Hospital for the years 1958-1988 were reviewed. Three ocular cancers were found to predominate: 1) choroidal melanoma, 2) retinoblastoma, and 3) squamous cell carcinoma. Epidemiologic distribution of the population is presented and compared to that of tumors commonly seen in general ophthalmic practice.     

Treatment of retinoblastoma and choroidal melanoma

Retinoblastoma and choroidal melanoma are two malignant ocular tumours that still give rise to discussions about diagnosis, natural history with respect to metastasis an choice of treatment. The therapeutic problems are best solved within a multidisciplinary oncology team in which the ophthalmologist, ophthalmopathologist and the general pathologist play an important role.In most institutes for ophthalmology a patient with a tumour in or in the region of the eye, is first seen by a specialist for eye diseases, who is also a surgeon in this field. In general the ophthalmologist decides on the diagnosis, the treatment and the follow-up without consulting other specialists in oncology. This solely ophthalmological approach can harbour a potential danger for the patient. Decisions on treatment made in a multidisciplinary team of specialists trained in oncological principles are responsible for the best results. Surgery combined with radiotherapy and chemotherapy can be a better choice than surgery alone, but even when surgery alone seems the best treatment, the discussion with the members of an oncological team can be of importance for the surgeon. The natural history of the tumour which includes the growth patterns, the growth rate and the tendency to metastasize may influence the choice of the surgical procedure; surgical intervention might be more or less extensive than previously foreseen.Dr. W.A. Manschot, professor in ophthalmic pathology, rightly advocates the contribution of the ophthalmopathologist to such an oncological team, because such a person has acquired knowledge in histopathology of the ocular tumours and experience in evaluating international literature in this field, the results of the treatment of groups of patients with the same tumour and publishing the statistically verified conclusions.As a chairman of the Dutch Eye and Orbit Tumour Committee Manschot was one of the enthousiastic initiators of its meetings of ophthalmologists, ophthalmic and orbital surgeons, radiotherapists, pathologists and medical oncologists.Two tumours have his special attention: the retinoblastoma and the choroidal melanoma.     

Screening for uveal melanoma metastasis. Literature review

Local tumour control in uveal melanoma has improved in the last decades. However, 5-year mortality due to metastases from large uveal melanomas remains high. Recently both isolated liver perfusion therapy and chemotherapy have reached encouraging results in improving metastasis survival. As such screening at an early stage, especially for liver metastases, becomes imperative.     

Brachytherapy of intra ocular tumors using ‘BARC I-125 Ocu-Prosta seeds’: An Indian experience

Aim:

To report our experience of brachytherapy using ‘BARC I-125 Ocu-Prosta seeds’ for the management of intraocular tumors with regard to tumor control, globe preservation visual outcome, and patient survival at Sankara Nethralaya, Chennai, India between September 2003 and May 2011.

Materials and Methods:

We reviewed records of 35 eyes of 35 patients who underwent ophthalmic brachytherapy between September 2003 and May 2011. Twenty-one cases had choroidal melanoma, nine had childhood retinoblastoma, two had adult-onset retinoblastoma, and there were one case each of vasoproliferative tumor, retinal angioma, and ciliary body melanoma. Brachytherapy was administered using a 15- or 20-mm gold plaque with or without a notch. Brachytherapy was the primary treatment modality in all tumors other than retinoblastoma, wherein brachytherapy was done post chemoreduction for residual tumor.

Results:

For choroidal melanomas, the mean radiation dose was 68.69 ± 15.07 (range, 47.72-94.2) Gy. The eye salvage rate was 13/20 (65%) and tumor control rate was 16/20 (80%) at an average follow-up of 24.43 ± 24.75 (range, 1.5-87.98) months. For retinoblastoma, the mean dose was 45.85 ± 3.90 (range, 39.51-50.92) Gy. The eye salvage rate and tumor control rate was 5/6 (83.3%) at an average follow-up of 38.36 ± 31.33 (range, 4.14-97.78) months. All eyes with retinoblastoma needed additional focal therapy for tumor control and eye salvage.

Conclusion:

The results of this retrospective study confirms that the use of ‘BARC I-125 Ocu-Prosta seeds’ in episcleral plaques to treat intraocular tumors offers a viable option for the management of intraocular cancers.     

Hepatische Filiae bei CUP („cancer of unknown primary“) und schmerzhafter Amaurose

A 63-year-old woman presented with a 9-month history of painful amaurosis of the left eye caused by hemophthalmos. She was already undergoing chemotherapy for histopathologically proven liver metastases caused by an assumed melanoma. The location of the primary tumor was unknown. Whole-body FDG-PET/CT staging identified a lesion with characteristically malignant uptake in the region of the left eye as the primary tumor. After enucleation, a primary uveal melanoma was verified that expressed the serological marker melanoma inhibitory activity (MIA). FDG-PET/CT was able to successfully align hepatic metastases due to CUP with local ophthalmologic diagnostic findings and led to a correct diagnosis.     

Clinico-pathological Correlations: Posterior Compartment of the Eye and Orbit

Diseases of the posterior compartment and the orbit are characterised by histological findings, most of which can be reproduced clinically. Examples are the examination of calcifications in retinoblastoma by ultrasonography. In the present review, histological findings of tumour and other diseases of the posterior ocular compartment and the orbit are presented and correlated with the clinical pictures and imaging techniques: uveal melanoma, choroidal nevus, choroidal metastases, choroidal hemangioma, retinoblastoma, Coat's disease, sympathetic ophthalmia, pleomorphic adenoma (benign mixed tumour) of the lacrimal gland, dacryoadenitis, lymphoma, rhabdomyosarcoma, Langerhans cell histiocytosis, orbital metastases, and phthisical eyes. Histopathology is usually the gold standard for a definitive diagnosis. It is very important for residents and those in training to become familiar with clinico-pathological correlations as these provide insight in pathophysiological processes. Regarding ophthalmic surgery, ophthalmic pathology offers the possibility to study wound healing and complications. A close collaboration between clinicians and ocular pathologists allows for an optimised processing of the submitted tissue and diagnosis. Thus, pre- and postoperative care can also be improved. This outstanding knowledge that ophthalmologists have gained over the last decades and beyond, should be preserved and passed on to the next generations in order to maintain a high standard in ophthalmological care.     

Intraocular metastasis from cutaneous malignant melanoma

Metastatic melanoma to the eye can show a number of unusual features. Two cases with intraocular metastases from primary cutaneous malignant melanoma, with a latency of 5 and 16 years, respectively, from excision to debut of ocular symptoms are reported. In the first case, tumour cell invasion of the chamber angle caused an advanced secondary glaucoma. This eye was enucleated some months later when the tumour extended through the sclera despite palliative external radiation therapy. In the other seeing eye, small melanoma metastases were treated with laser. The patient died of systemic involvement. In the second case, a probable melanoma metastasis was revealed by a vitrectomy of a thickened posterior vitreous membrane. Ophthalmoscopy and B-scan ultrasonography 8 months later showed growths projecting 2 mm into the vitreous cavity. Metastases from a malignant melanoma with infiltration of the retina forming nodules, but also affecting adjacent choroid and optic nerve, was disclosed by histology. The patient died of metastasis to the brain.     

Diagnosis and management of cancer metastatic to the uvea: a study of 70 cases.

Although metastatic cancer to the uvea is reported to be the most common intraocular malignancy, most ophthalmologists have had little experience with its diagnosis and treatment. This report describes our experience with the diagnosis and management of 70 patients with metastatic cancer to the uvea. Many patients were evaluated with modern diagnostic modalities such as fluorescein angiography, ultrasonography, and the 32P test when indicated. Thirty-one percent of patients had no history of previous malignancy, and the ocular complaints represented the first symptoms of systemic cancer. The ocular malignancy often simulated better-known ophthalmic entities, and the referring diagnosis was correct in only 38% of cases. This series, therefore, reflects the clinical problem confronting the practicing ophthalmologist. About one-half of the patients were treated with external beam irradiation to the involved eye(s), which often resulted in dramatic resolution of the tumor and visual return. Other patients had either no treatment, chemotherapy, or enucleation in selected instances.     

Intravitreal chemotherapy and laser for newly visible subretinal seeds in retinoblastoma

Background: There has been no effective method for treating newly visible (“new”) subretinal seeding in retinoblastoma except enucleation. The objective of this report is to determine whether intravitreal chemotherapy combined with 810 nm indirect laser can successfully treat retinoblastoma eyes with “new” subretinal seeding which appeared after intra-arterial chemotherapy (ophthalmic arterial chemosurgery: OAC).

Material and Methods: Single center retrospective study from a tertiary cancer hospital of a case series of 14 eyes treated with combined intravitreal chemotherapy and laser from 2012 to 2017. Ocular salvage, patient survival, recurrence-free ocular survival, metastases, and extraocular extension were assessed.

Results: A total of 14 eyes in 13 unilateral or bilateral retinoblastoma patients with “new” subretinal seeding after initial eye salvage therapy were treated with combined intravitreal injection of melphalan (30 ug) or melphalan (30 ug) and topotecan (20 ug) and with 810 nm indirect continuous wave laser. All eyes were salvaged. Only two eyes (14%) recurred again for subretinal seeds after 6 and 8 months, respectively, and required additional cycles of intravitreal injections and laser. Combined intravitreal injection of melphalan or melphalan plus topotecan with 810 nm indirect continuous wave laser was not associated with any metastatic events, patient deaths, extraocular extension, or need for enucleation.

Conclusion: There has been no effective treatment for “new” subretinal seeding after OAC except enucleation or second course OAC. Combined intravitreal chemotherapy with 810 nm indirect laser may be an effective and safe alternative to enucleation.