The site of origin of a histologically documented carcinoma is not identified clinically in approximately 3% of patients; this situation is often referred to as carcinoma of unknown primary (CUP) origin or occult primary malignancy.[1,2,3,4,5,6]
Prognosis and Survival
The definition of a CUP varies from study to study; however, at a minimum, this determination should include a biopsy of the tumor and a thorough history and complete physical examination that includes head and neck, rectal,...
Enucleation for large intraocular tumors, followed by risk-adapted chemotherapy when the eye cannot be saved.
Conservative ocular salvage approaches when the eye and vision can be saved.
Chemoreduction with either of the following:
Systemic chemotherapy with subtenon chemotherapy.
Ophthalmic artery infusion chemotherapy.
Local treatments including cryotherapy, thermotherapy, and plaque radiation therapy.
External-beam radiation therapy (EBRT).
Enucleation followed by chemotherapy
Because unilateral disease is usually massive and often there is no expectation that useful vision can be preserved, up-front surgery (enucleation) is commonly performed. Careful examination of the enucleated specimen by an experienced pathologist is necessary to determine whether high-risk features for metastatic disease are present. These features include the following:[1,2,3,4,5]
Anterior chamber seeding.
Massive choroidal involvement.
Tumor beyond the lamina cribrosa.
Scleral and extrascleral extension.
Pre-enucleation magnetic resonance imaging has low sensitivity and specificity for the detection of high-risk pathology.
Systemic adjuvant therapy with vincristine, doxorubicin, and cyclophosphamide or with vincristine, carboplatin, and etoposide has been used to prevent the development of metastatic disease in patients with certain high-risk features assessed by pathologic review after enucleation.[3,7,8]; [Level of evidence: 2A]
Conservative ocular salvage approaches
Conservative ocular salvage approaches, such as chemotherapy and local-control treatments, may be offered in an attempt to save the eye and preserve vision. Ocular salvage rates correlate with intraocular stage. In selected children with unilateral disease, the Reese-Ellsworth (R-E) Group was correlated with ocular outcomes. While the possibility of saving the eye without the use of EBRT was greater than 80% for children with R-E Group II or III disease, the ocular outcomes for children with R-E Group V eyes were poor, with less than 40% ocular salvage rates, even after the use of EBRT.
Caution must be exerted with extended systemic chemotherapy administration and delayed enucleation when tumor control does not appear to be possible, particularly for Group E eyes. Pre-enucleation chemotherapy for eyes with advanced intraocular disease may result in downstaging and underestimate the pathological evidence of extraretinal and extraocular disease, thus increasing the risk of dissemination.