Jill Broffman, M.D.

The following case presents a patient who develops a retinal vein thrombosis, undergoes an extensive evaluation for risk factors, then returns one year later with non-Hodgkins lymphoma.

Case Report

A 52-year-old female presented with loss of vision in her left eye. This sole symptom occurred over several days, was painless, and affected central, but not peripheral vision. Her right eye was unaffected. She was otherwise healthy, with previous medical history significant only for menopause, 50 pack-years smoking and benign colonic polyps. Recent mammogram, PAP and colonoscopy were negative. Her family history was significant for ovarian and breast cancer in her mother and maternal grandmother. There was no family history of bleeding or coagulation disorders.

Her exam was remarkable only for left vision loss with fundoscopic findings of a dilated branch of the retinal vein and small, localized hemorrhages. Routine labs were essentially normal. Chest radiograph showed a large mass in the right cardiophrenic angle and changes consistent with chronic obstructive pulmonary disease. Chest CT confirmed a benign appearing pericardial cyst and obstructive lung disease. Additional tests for hypercoagulable state and autoimmune diseases were negative.

Patient was diagnosed with a left branch retinal vein thrombosis. Her visual loss stabilized after several laser photocoagulation treatments, and subsequently her vision has gradually improved.

One year after the retinal vein thrombosis, she returned with a 5-week history of enlarging and recently painful masses in her groin area. Thinking they would go away, she deferred evaluation until the largest mass was pressing on her thigh and causing significant pain. She denied fevers, chills, weight loss, fatigue or cough. Exam was remarkable for a 4 cm by 5 cm, firm, non-tender right inguinal mass and several smaller bilateral inguinal masses. There was no hepatosplenomegaly or other adenopathy noted. Fine needle aspirate and excisional biopsies revealed a nodular small cell lymphoma. Additional tests confirmed a clinical stage II lymphoma and the patient was started on chemotherapy and radiation.

Discussion

Retinal vein thrombosis (RVT) is a common cause of retinal vascular disease second only to diabetic retinopathy. Affected patients are most often older than 40 years, and they frequently have an underlying systemic disease. RVT in patients younger than 40 years is much less common and has a low incidence of associated conditions. Systemic disorders that are associated with an increased risk of RVT in older patients include hypertension, diabetes, malignancies, vasculitis, hypercoagulopathies and hyperviscosity syndromes.¹

It is uncertain as to what extent a patient with RVT should be evaluated for possible underlying diseases. Some studies suggest an aggressive evaluation in children with RVT, while others recommend intensive work up only in adults presenting with bilateral or recurrent RVT.^2,3 It remains a challenge for the primary care physician to determine the appropriate evaluation for occult systemic disease when a low risk patient develops a RVT.

This patient had several risk factors for malignancy related to heavy smoking, past colon polyps and a strong family history of ovarian and colon cancer. Therefore, when she developed the RVT in the absence of diabetes or hypertension, but with the risk factors above, an occult malignancy was suspected. A thorough evaluation failed to uncover an occult disease before its clinical presentation one year later. Less than 7% of non-Hodgkin\'s lymphoma patients have ocular involvement. Only a few cases have been reported in which a patient presents with the RVT prior to clinically apparent non-Hodgkin\'s lymphoma.⁴ The most common type of ocular involvement is direct tumor infiltration; second is compression of ocular structures or vasculature by an enlarging CNS mass; third is in association with hypercoaguable or hyperviscosity syndromes. The RVT in this case may have been related to abnormal clotting associated with an (as of then) undetectable malignancy, unmeasured hyperviscosity or other risk factors such as smoking and chronic pulmonary disease which are associated with thrombosis.

There are few case reports of RVT in patients with non-Hodgkin\'s lymphoma due to abnormal coagulation or elevated serum viscosity and a few more with combined retinal artery and retinal vein throm-bosis.^4,5,6 A number of reports cite paraproteinemias, blood dyscrasias, autoimmune disorders and malignancies as the cause of a hypercoagulopathy or hyperviscosity syndrome, which was responsible for the RVT.^4,5,7

In the case presented, laboratory results did not detect either a hypercoagulable state or hyperviscosity syndrome, and it remains controversial as to what constitutes the appropriate evaluation for patients with a RVT. Some suggest a limited evaluation for hypertension and diabetes, while others recommend a more comprehensive search for occult diseases. Perhaps those under 60 years of age with other risk factors (such as prior cancer, smoking history or family history of cancer) should be screened for other malignancies, and followed up at regular intervals. Even if an extensive evaluation for underlying malignancy is not undertaken, patients should be educated about any risk factors, and to remain vigilant and report any unusual signs and symptoms to their physician. This may lead to earlier diagnosis and a more favorable prognosis than conventional follow-up visits in selected high-risk individuals.

Hayreh recently published a prospective review of 1090 consecutive patients with retinal vein occlusion and reported the prevalence of associated systemic diseases.⁸ They found that the prevalence of systemic disease varied with the type of retinal vein occlusion and recommended categorizing patients into six groups: non-ischemic and ischemic central retinal vein occlusion, non-ischemic and ischemic hemi-central retinal vein occlusion and major and macular branch retinal vein occlusion. They recommended that generalizing about the group as a whole was misleading, and that apart from a routine medical evaluation, extensive and expensive work-ups for systemic diseases is unwarranted for the great majority of patients with this problem. Furthermore, the presence of an association with systemic disease does not necessarily imply a cause and effect relationship.

The case reported was instructive. Despite an extensive negative work-up, the patient delayed reporting significant, progressive new symptoms for more than a month, \"hoping that it would go away.\" Even with earlier detection, the outcome benefit remains to be determined.

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