Choroidal Metastasis from an Occult Primary
A 35-year-old female presented with pain in the right eye since 6 months with gradual diminution of vision in that eye since the last 2 months, which had progressed to a complete loss of vision since 15 days. The pain was dull, aching, referred to the forehead and unaccompanied by redness, discharge or coloured halos. For the last one week, she had also noticed redness in the nasal aspect of the right eye. There was no other significant ocular or systemic history.
A detailed ophthalmic examination of the right eye revealed no perception of light, intraocular pressure by applanation tonometry was 32.0 mm Hg, and there were prominent sentinel vessels medially [Figure - 1]. There was a total bullous retinal detachment and a superonasal non-pigmented mass lesion on fundus examination. Transillumination of the right eye was positive in all four quadrants. There was an afferent pupillary defect. The left eye was normal.
B-Scan ultrasound of the right eye showed a well-defined hyperechoeic choroidal mass in the superonasal quadrant, along with a small satellite lesion temporal to the optic nerve, with overlying total retinal detachment [Figure - 2]. The corresponding A-scan image revealed a high preretinal spike with very low internal reflectivity.
A detailed systemic work-up by the internist was ordered. There was no apparent breast lump or pulmonary finding. Per-rectal examination revealed nodules in the Pouch of Douglas (POD).
Differential diagnoses would include:
a) Intraocular metastasis
b) Choroidal melanoma
c) Choroidal haemangioma
Likely causes of pain are:
a) Secondary glaucoma
b) Involvement of the ciliary nerves by the tumour
Likely causes of visual loss are:
a) Retinal detachment
b) Involvement of the optic nerve
Keeping in mind the non-pigmented mass, positive transillumination and nodules in the POD, a diagnosis of atypical choroidal metastasis was considered.
This case is remarkable for several unusual features of choroidal metastasis. The classically described features are: [1},[2},[3}
a) Older age
e) Posterior pole masses
This patient presented with unusual features of:
a) Uniocular pain
b) Sentinel vessels
c) Secondary glaucoma
d) A large choroidal mass with a satellite lesion
These characteristics are more commonly seen in malignant melanomas rather than choroidal metastases.
In cases of choroidal metastasis, the breast is the most common site of primary cancer in women, followed by the lungs. In men, the lungs are the most common sites of primary malignancy.[1},[2},[3}
What investigations should be carried out in a case suspected to harbour a choroidal metastasis?
A thorough systemic investigation should be carried out to search for the likely primary site. It should include a complete blood count, liver, renal and thyroid function tests, chest skiagram, abdominal and pelvic ultrasound, and mammogram. In case all these are negative, a whole body CT scan and bone scan should be ordered.
In this case, a battery of investigations was ordered to hunt for the primary malignancy. Haematological and routine investigations for liver functions, renal functions, and thyroid functions were normal. Stool was negative for occult blood. Chest skiagram revealed diffuse cannon ball metastases ([Figure - 3], left). Mammogram was normal. Ultrasound of the abdomen showed multiple hypodense lesions in the liver suggestive of target lesions, with no mass lesion detected elsewhere. Pelvic ultrasonography revealed an enlarged right ovary and deposits in the POD ([Figure - 3], right). An ultrasound-guided fine needle aspiration cytology (FNAC) of the right ovary revealed no malignant cells. A whole body CT scan with 5.0 mm cuts was ordered which revealed metastatic deposits in both the lungs, abnormal echotexture of the liver, deposits in the pelvic region, but no evidence of the primary tumour.
Shields et al[3} in their experience of 520 eyes with choroidal metastasis, noted that 34% of patients gave no previous history of cancer. In approximately half of these (17%), the primary site remained undiagnosed in spite of extensive systemic investigations. Similar experiences have been found in other series of such patients.[4},[5}
Radiotherapy to the eye and chemotherapy of the primary is the standard method of care.[3}
Volpe & Albert[6} have defined three sets of patients who benefit from enucleation.
1. Palliative - Largest group - painful blind eyes due to secondary glaucoma.
2. Curative- Those with solitary tumour / low-grade metastasis- Resection of the tumour and enucleation of the eye may be curative.
3. Diagnostic- When primary amelanotic melanoma cannot be ruled out.
Is enucleation in such cases, a justifiable treatment option for the developing world?
Given the cost/benefit ratio of a search for an unknown primary, the implications for the developing world are daunting. Elaborate investigations using radiological studies focussed on identifying primary tumour sites offer little benefit to the vast majority of patients. Relatively specific immunohistochemical tests may be required to help identify the exact origin of metastatic tumours. These techniques require adequate malignant tissue for optimum results. Enucleation of the painful blind eyes seems justified for this purpose, especially in developing countries, where lack of optimum imaging facilities may not permit ultrasonic or fluoroscopic-guided sampling of metastatic foci. An extensive search for primary malignancies involves considerable medical risk and expense, yet is often unable to locate the primary tumour or improve the response to therapy or quality of life.[7},[8} The aim should be to identify curable patients while avoiding unnecessary efforts and discomfort for untreatable patients.
However, it must be kept in mind that appropriate chemotherapy for the primary tumour will usually melt the metastatic tumour also, and save the patient from cosmetic disfigurement. Also, often the primary tumour may be of the same size as the metastatic foci, and it could in fact be in the same organ as the metastasis.
Faced with no choice, in this patient, the painful blind right eye was enucleated [Figure - 4] for symptomatic relief and in the hope of obtaining tissue for histopathology that might help in finding the primary site of cancer. The final tissue diagnosis was mucinous papillary adenocystoid carcinoma [Figure - 5]. The tumour cells of the specimen were subjected to immunohistochemistry and were positive for Mucicarmine and Carcino-Embryonic Antigen (CEA), suggesting a primary in the gastrointestinal tract, breast or thyroid. Despite further investigation of these organs, the primary remained elusive.
Adenocarcinomas account for up to 60% of all metastatic neoplasms from an unknown primary site.[9} When identification of the primary tumour is impossible, a therapeutic trial remains the only method to determine if patients have responsive tumours. A fair response to combination therapy can be expected in breast, ovarian and prostatic cancer, while metastatic gastrointestinal or urogenital tumours remain difficult to treat.[7} Evaluation of a patient with an occult primary cancer should be structured in such a way that it can quickly distinguish treatable tumours from those that need only palliation so as to avoid prolonged testing.
The oncologist was consulted and chemotherapy (Adriamycin and 5-Fluorouracil) directed towards adenocystoid carcinoma was started in this patient. The response was poor and follow-up at 3 months revealed an increase in the size of the right ovary, free fluid in the pelvis, and enlargement of the target lesions in the liver. The patient has since been lost to follow-up.
Metastatic carcinoma from an unknown primary site accounts for 3-5% of all newly diagnosed malignant lesions.[1}[0} Although 85% of patients die within a year of diagnosis, 5-10% of them may be long-term survivors.
How common is it for an occult malignancy to present with ocular signs and symptoms alone?
This is an uncommon occurrence. The incidence of ocular metastasis in patients dying of all cancers is about 10%.[6}
An occult malignancy presenting with ocular signs and symptoms alone is a rare occurrence. When it occurs with atypical features as in this case, a correct diagnosis becomes even more important. A high index of suspicion is required to clinically detect systemic malignancies from the ophthalmological findings. In future, improved diagnostic modalities may help in detecting the primary tumour more frequently, but where not possible, judicious use of limited resources for chemotherapy in such patients may be more important than elaborate investigations.