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.     

Ophthalmic manifestations, cytology, immunohistochemistry, and molecular analysis of intraocular metastatic T-cell lymphoma: report of a case and review of the literature

We report a case of T-cell lymphoma metastatic to the eye, with an accompanying review of the literature. A 78-year-old white male with bilateral vitritis was diagnosed with primary cutaneous peripheral T-cell lymphoma unspecified, via vitreous biopsy. The tumor was found to be clonally related to the prior cutaneous malignancy using cytology, immunophenotyping, and molecular analysis. The vast majority of primary intraocular lymphomas are malignant B-cells, whereas intraocular T-cell lymphomas are uncommon. This case demonstrates the utility of immunophenotyping and molecular analysis with microdissection and polymerase chain reaction, as critical adjunctive studies, in patients presenting with a masquerade syndrome, and later diagnosed with T-cell intraocular lymphomas. Vitreo-retinal without uveal involvement in this case, similar to many ocular metastatic T-cell lymphomas reported in the literature, is particularly intriguing because the uvea, not retina, is the typical ocular tissue involvement in the majority of metastatic B-cell lymphomas.     

Ocular manifestations of cancer

Cancer may affect the eye and orbit as a direct result of metastatic neoplastic infiltration, compression, or circulating antibodies involving paraneoplastic retinal degeneration. A metastatic tumor to the uvea is the most common form of an intraocular metastatic process. The choroid is the most common site for uveal metastasis; metastases to the ciliary body, iris, retina, optic disk, and vitreous are rare. Approximately one-third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung carcinomas for women and lung and gastrointestinal carcinomas for men most commonly metastasize to the eye and orbit. The short-term prognosis for vision is usually good after an individualized therapeutic approach (chemotherapy, hormonal therapy, external beam radiotherapy, or plaque radiotherapy), but the systemic prognosis is poor. The visual paraneoplastic syndromes encompass several distinct clinical and pathological entities including carcinoma-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse melanocytic uveal proliferation (BDUMP). The CAR syndrome affects photoreceptors, MAR is thought to affect bipolar cell function, and BDUMP targets the uveal tract. Identification of circulating antibodies against retinal proteins (recovering, 23-kDa retinal protein; 46-kDa and 60-kDa retinal proteins) serves to recognize the paraneoplastic nature of the patient's symptoms, which frequently develop before the cancer is diagnosed. Anecdotal therapeutic responses are described after systemic steroids, immunoglobulin injection, and plasmapheresis. Recognition of their visual symptoms and ocular findings should alert the ophthalmologist to the possibility of cancer and systemic evaluation should be pursued.     

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.     

Incidence and clinical characteristics of symptomatic choroidal metastasis from breast cancer

PURPOSE: To determine the clinical incidence and characteristics of symptomatic choroidal metastasis (CM) in breast cancer. METHODS: Forty-six consecutive patients with CM from breast cancer were retrospectively reviewed in respect of ocular findings, medical history and systemic disease. Clinical incidence of CM was determined and compared with the incidence predicted from prevalence data obtained in ocular screening studies. RESULTS: Choroidal metastasis occurred with a median interval of 42.4 months after diagnosis of breast cancer and was predominantly unilateral (63% patients) and solitary (57% affected eyes). A total of 32% of patients had no history of metastatic tumour disease, but systemic screening with CT and scintigraphy revealed metastatic disease in 100% of patients. A median number of three other organs were affected by metastasis. Median survival from diagnosis of CM was 13.1 months. The mean number of local patients diagnosed with CM was 2.9 per year, which was one order of magnitude less than predicted from clinical screening studies. CONCLUSIONS: Choroidal metastasis occurs in advanced metastatic breast cancer, indicating a grave vital prognosis. In a minority of patients (32%) it is the first sign of metastatic disease. The clinical incidence of CM is far smaller than predicted from prevalence data obtained from ocular screening studies.     

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.     

Risk factors for metastasis in retinoblastoma.

Children with retinoblastoma typically survive their cancer due to advances in early diagnosis and treatment. Despite this success, risk factors persist for metastasis that are thought to be related to patient age, sex, laterality, treatment, genetics, histopathology, and extraocular extension. This review has found that invasion of the uvea, orbit, and optic nerve continue to be the most important predictors of metastatic retinoblastoma. Bilaterality and delays in diagnosis are also important factors. We examine molecular and genetic studies that offer the potential of predicting which tumors are likely to metastasize, which will recur within the eye, and which will undergo senescence. In this review, we describe which clinical evaluations, genetic studies, and histopathologic evaluations of retrieved specimens are currently used widely. This review has been performed to help those caring for patients with retinoblastoma and to aid informed consent.     

Clinical characteristics of metastatic orbital tumors

The authors reviewed the clinical and histopathologic records of 38 patients with metastatic orbital tumors. Diplopia, ocular motility limitation, and mass effect with displacement, proptosis, or palpable mass were common signs and symptoms. Enophthalmos occurred in 25% of cases. The authors found that the clinical presentations could be broken down into four generalized syndromes of presentation: infiltrative (20 cases, 53%); mass (14 cases, 37%); inflammatory (2 cases, 5%); and functional (1 case, 3%). An infiltrative pattern of presentation may be a clue to the metastatic nature of the orbital tumor. There may be no history of systemic cancer; in 25% of the patients in this series, the orbital tumor was the initial manifestation of systemic disease. Although the prognosis is poor for patients with metastatic cancer (average survival in this series, 10.2 months), modern treatment methods continue to improve and long-term palliation is often possible. The ophthalmologist plays a vital role in the diagnosis, histologic evaluation, and referral of these patients.     

Ocular manifestations of cancer.

Cancer may affect the eye and orbit by a direct effect of metastatic neoplastic infiltration or compression or by circulating antibodies involving paraneoplastic retinal degeneration. Metastatic tumor to the uvea is the most common form of an intraocular malignant process. The choroid is the most common site for uveal metastasis; metastases to the ciliary body, iris, retina, optic disc, and vitreous are rare. Approximately one third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung carcinomas for women and lung and gastrointestinal carcinomas for men most commonly metastasize to the eye and orbit. The short-term prognosis for vision is usually good but the systemic prognosis is poor. The visual paraneoplastic syndromes encompass several distinct clinical and pathologic entities including carcinoma-associated retinopathy, melanoma-associated retinopathy, and bilateral diffuse melanocytic uveal proliferation. The first affects photoreceptors, the second is thought to affect bipolar cell function, and the third targets the uveal tract. Identification of circulating antibodies against retinal proteins (recoverin, 23-kD retinal protein; 46-kD and 60-kD retinal proteins) serves to recognize the paraneoplastic nature of the patient's symptoms, which frequently develop before the cancer is diagnosed. No therapy exists to stop the inexorable progressive loss of vision. Metastasis to the eye and orbit and paraneoplastic disorders represent a very bad prognostic sign. Recognition of their visual symptoms and ocular findings should alert the ophthalmologist to the possibility of cancer and systemic evaluation should be pursued.     

Ocular presentations of breast cancer

CONTEXT: Breast cancer is the most common malignancy in women, with increasing incidence in Europe and North America. The frequency of involvement of the eye and visual pathways is reported to be as high as 30% in patients with known metastatic disease. In some cases, ophthalmic involvement can be the first sign of metastatic spread. Metastasis occurs via the haematogenous route and predominantly involves the choroid. Metastases to other ocular structures, the orbit and the visual pathways have also been described. Paraneoplastic effects are rare but significant. TREATMENTS: Different modalities are employed in the treatment of breast cancer and its metastases. These include chemotherapy and radiotherapy. The ocular adverse effects of these have been well described, but recently developed new treatment modalities, such as monoclonal antibodies, may have different side-effects. With the increasing incidence of breast cancer and the advent of new treatment strategies, the complications of the disease and the sequelae of therapy are highly relevant to both oncologists and ophthalmologists.     

Clinical, histologic, and immunohistochemical evaluation of iris metastases from small cell lung carcinoma

CASE REPORT: We report the case of a patient with small cell lung carcinoma who developed multiple metastases in the iris. The eye was enucleated after failure of a conservative approach. The specimen underwent histologic and immunohistochemical evaluation that confirmed the diagnosis. COMMENTS: Metastatic carcinoma is the most common form of intraocular malignancy, and breast is the most prevalent primary location, followed by lung. Small cell lung carcinoma constitutes 23.1% of lung neoplasias. It has a significantly worse prognosis than non-small cell carcinoma due to its propensity for early and widespread dissemination. Uveal metastases involve the choroid more often than the iris and ciliary body, probably because the arterial distribution is more abundant in the posterior than in the anterior uvea. Iris involvement represents only 9% of the metastatic uveal tumours.     

22例眼眶转移癌临床病理分析

目的探讨眼眶转移癌的临床特征和原发部位。设计回顾性病例系列。研究对象22例眼眶转移癌患者。方法分析1999～2007年武警总医院眼眶病研究所22例眼眶转移癌患者的临床、影像学和病理诊断资料。主要指标临床表现、影像学表现、病理形态学表现、原发部位。结果22例眼眶转移性肿瘤中原发肿瘤来自乳腺6例(27.3%),肺癌5例(22.7%),来源未明低分化腺癌3例(13.6%),肝癌2例(9.1%),甲状腺癌、宫颈癌、直肠类癌、下肢恶性黑色素瘤、腹膜后恶性副神经节细胞瘤及神经母细胞瘤各1例。女性13例,男性9例,平均年龄50.2岁(中位数年龄51岁,范围6～67岁)。病变位于右眼眶11例,左眼眶5例,双侧眼眶1例,同侧眼内加眶内转移2例,眶颅沟通3例。最常见的症状为视力下降、其次是眼球运动不良、眼球突出、眼痛和眼睑肿胀。10例(45.5%)眼部表现是首发症状,3例(13.6%)未找到原发灶。结论眼眶转移性肿瘤来自乳腺占第一位,其次是肺癌和来源不明的低分化腺癌。部分病例眼部症状为首发症状。(眼科,2007,16:403-406)     

Choroidal metastasis: case reports and review of the literature.

BACKGROUND: Choroidal metastases are recognized as the most common intraocular malignancy. Their diagnosis has become more common due to increased emphasis on comprehensive eye examinations for cancer patients and the improved life expectancy of patients with metastatic disease. They are most prevalent in female patients with breast cancer and male patients with lung cancer. METHODS: A thorough fundus examination, coupled with the use of A-scan and B-scan ultrasonography, will aid in their diagnosis. There are many ways of treating these tumors, including radiation therapy, chemotherapy, and monitoring. CASE REPORTS: Two case reports of patients diagnosed with choroidal metastases are discussed. Case 1 involved a patient with lung cancer who manifested a large bullous exudative retinal detachment due to an underlying choroidal metastasis. Case 2 dealt with treatment of a patient with metastatic transitional cell cancer who manifested a shallow exudative retinal detachment caused by a choroidal metastasis. CONCLUSIONS: Due to progress of chemotherapeutic medications, the number of patients who manifest choroidal metastases will continue to increase. It is essential for the practitioner to be able to recognize this disease process to prevent visual loss and institute referral for proper treatment for metastatic disease.     

Carcinoma metastatic to the eye

Cancer is a leading cause of death in America. Cancer to the eye is being diagnosed with increasing frequency. It is now considered the most common intraocular malignancy in adults. Although most ocular metastases do not require treatment, they have important prognostic implications for the patient's overall survival. Diagnostic errors leading to enucleation could be reduced if the incidence of metastatic tumors was always well considered. Presented here are two patients with metastatic tumors and a brief discussion of the nature of this ocular disease.     

Intraocular lymphoma

There are two distinct forms of intraocular lymphoma. One originates within the central nervous system (CNS) and is called primary CNS lymphoma. The second form arises outside the CNS and metastasizes to the eye. When primary CNS lymphoma initially involves the retina, it is named primary intraocular lymphoma (PIOL). Although PIOL is a rare malignancy, the incidence has dramatically increased in the past 15 years. Typical clinical manifestations include blurred vision and floaters. Ophthalmic examination reveals vitreitis and subretinal infiltrates. Diagnosis of PIOL can be difficult and requires neuroimaging, examination of the cerebrospinal fluid and/or vitreous. Molecular analysis detecting immunoglobulin gene rearrangements and ocular cytokine levels showing elevated interleukin (IL)-10 with an IL-10 to IL-6 greater than 1.0 are helpful adjuncts for the diagnosis. Treatment includes systemic chemotherapy and radiation with current regimens favoring the use of chemotherapy first. In contrast, metastatic systemic lymphoma, like other metastatic ocular tumors, is usually confined to the uvea, in particular the choroid. Compared with PIOL, metastatic systemic lymphomas have a much lower prevalence, better prognosis, and are less likely to create a diagnostic dilemma.     

Sympathetic ophthalmia in Singapore: new trends in an old disease

Background Sympathetic ophthalmia (SO) is an uncommon uveitic condition that occurs after injury to the uvea of one eye and may occur after accidental ocular trauma or ocular surgery. We sought to investigate the common causes of SO in Singapore and the demographic profile as well as the final visual acuity after treatment in these patients. Methods This was a retrospective, non-comparative case series in which patients with SO were identified from the Singapore National Eye Centre uveitis database in the period between 1993 and 2003. The patients' case records were examined for a history of ocular trauma or surgery and subsequent development of bilateral or contralateral uveitis consistent with SO or histopathological evidence of SO in enucleated eyes. The medical records of these patients were reviewed for details of the inciting event, presentation, treatment, and visual acuity. Results A total of ten patients (six men and four women) were diagnosed with SO in the period of study. SO occurred after accidental trauma in three patients and following ocular surgery in seven. Vitreoretinal surgery was responsible for four of these cases, and diode laser cyclophotoablation for another two, whereas neodymium:yttrium–aluminium–garnet (Nd:YAG) laser cyclotherapy was the cause in the last patient. Overall, six of ten patients underwent at least one vitreoretinal procedure. Four of the patients had a final visual acuity of 6/15 or better, whereas five had a visual acuity of 6/30 or worse. Good final visual acuity appeared to be associated with early initiation of immunosuppressive therapy. Conclusion In this series, ocular surgery, especially vitreoretinal surgery, had overtaken non-surgical trauma as the major cause of SO. A good outcome was possible in most cases if an early diagnosis was made and immunosuppressive treatment started promptly.     

Results of therapy for orbital malignant lymphoma

PURPOSE: To elucidate the clinical and histopathological features of orbital malignant lymphoma, and to develop a protocol for effective treatment. MATERIALS AND METHODS: The present study analyzed 18 cases of orbital lymphoma which were treated at Yamagata University Hospital over the last 14 years. The tentative strategy for choosing the treatment was to treat the cases of clinical stage I (Ann Arbor criteria) with curative intent and the cases of stage II-IV with palliative intent. RESULTS: Six patients had primary orbital lymphomas, 2 had secondary orbital lymphomas, and 10 had metastatic orbital lymphomas. Histopathologically, all the cases of primary lymphoma were of low-grade malignancy and all the cases of secondary lymphoma were of intermediate-grade malignancy. Of the metastatic lymphoma cases, 3 were of low-grade and 7 of intermediate-grade malignancy. The cases of primary lymphoma were Stage I and were treated by radiation or chemotherapy. The cases with secondary lymphoma were Stage II and were treated by both radiation and chemotherapy. The cases with metastatic lymphoma were Stage III or IV and were treated by chemotherapy and/or radiation. Control of orbital lymphoma was achieved in all 6 cases with primary lymphomas. Although the survival rate was 0% for secondary lymphomas and 50% for metastatic lymphomas, ocular complications were improved during the remainder of the patients' life. CONCLUSIONS: All the primary orbital lymphomas were treated effectively by radiation or chemotherapy. For secondary and metastatic orbital lymphoma, our strategy for treatment was beneficial by improving ocular complications and the quality of life.     

Incidence and clinical characteristics of symptomatic choroidal metastasis from lung cancer

Purpose: To determine the clinical characteristics of symptomatic choroidal metastasis (CM) resulting from metastatic lung cancer. Methods: Twenty‐two consecutive patients with symptomatic CM resulting from lung cancer were retrospectively reviewed for ocular findings, medical history and systemic disease. All patients underwent a complete screening for further organ metastasis by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was determined and compared with the incidence predicted from ocular screening studies. Results: In eight of 22 (36%; 95% confidence interval [CI] 17–59) patients, lung cancer had been diagnosed before occurrence of CM, with a median interval of 13 months. In 14 patients lung cancer was detected after diagnosis of CM, with a median interval of 1 month. Choroidal metastasis was unilateral, solitary and located close to or at the posterior pole in the majority of patients. Further organ metastasis with a median number of three affected organ systems was present in 19 (86%; 95% CI 65–97) patients. Median survival after diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung cancer patients with CM identified in an ocular screening study. The mean number of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was two orders of magnitude less than predicted from screening studies. Conclusions: Symptomatic choroidal lung cancer metastasis in the majority of patients presents as a solitary tumour before diagnosis of lung cancer in patients with multiple organ systems affected by metastatic disease. Contrary to predictions from ocular screening studies, it is a rare clinical entity.