The Absent-Minded Professor: An Unusual Complication of Melanoma

The Absent-Minded Professor: An Unusual Complication of Melanoma

Multidisciplinary Consultations on Challenging Cases

The University of Colorado Denver School of Medicine faculty holds weekly second opinion conferences focusing on cancer cases that represent most major cancer sites. Patients seen for second opinions are evaluated by an oncologic specialist. Their history, pathology, and radiographs are reviewed during the multidisciplinary conference, and then specific recommendations are made. These cases are usually challenging, and these conferences provide an outstanding educational opportunity for staff, fellows, and residents in training.

The second opinion conferences include actual cases from genitourinary, lung, melanoma, breast, neurosurgery, gastrointestinal, and medical oncology. On an occasional basis, ONCOLOGY will publish the more interesting case discussions and the resultant recommendations. We would appreciate your feedback; please contact us at

E. David Crawford, MD
Al Barqawi, MD
Guest Editors

University of Colorado Health Sciences Center
and Univeristy of Colorado Cancer Center
Denver, Colorado

The patient is a geology professor who was evaluated in our multidisciplinary cutaneous oncology clinic for a new diagnosis of malignant melanoma with subsequent development of metastatic disease and melanoma-associated retinopathy.


The patient initially presented to our clinic in 1998. At that time, he was a 57-year-old geologist with a history of extensive sun exposure who had a pigmented lesion biopsied from his right posterior auricular region. The pathology revealed a Clark’s level IV, 1.28-mm malignant melanoma. He subsequently underwent wide local excision with concurrent sentinel lymph node biopsy. The reexicison specimen revealed no residual melanoma, and three lymph nodes were removed, none of which showed any evidence of metastatic melanoma. After much discussion with the patient, he elected to enroll on an adjuvant clinical trial of interferon with or without tamoxifen. He was randomized to receive interferon alone. He received interferon at 3 million units subcutaneously three times a week for a total of 18 months. The patient tolerated this treatment well, with only fatigue as a complaint. He was then followed with close observation.

He did very well until May of 2002, when he began to complain of trouble with his vision. He reported yellow and white flashing lights and floaters. An optometrist initially evaluated him but found no etiology for these symptoms. Magnetic resonance imaging (MRI) of the brain was performed in June 2002 to further evaluate these symptoms. The scans showed no evidence of metastatic melanoma. Despite this initial negative workup, the patient continued to report worsening vision with persistent flashing lights as well as new symptoms of memory loss. He was therefore evaluated by ophthalmology. Because of his symptoms, there was concern about lymphoma as a possible cause, and therefore a vitreous biopsy was performed. The biopsy was interpreted as vitritis. The pathology revealed inflammatory white cells, no definitive pigment cells, and no lymphoma, and all cultures were negative.

Symptoms particularly worsened in September 2002, with progressive short-term memory loss and difficulty with verbal expression. The patient stated, “I am losing my mind.” A repeat MRI of the brain was performed, revealing a 5×4.4×4 cm left frontal hemorrhagic metastasis. He was admitted to neurosurgery and began therapy with steroids and antiepileptics. A left craniotomy with complete resection was performed, and the pathology was consistent with metastatic melanoma.

Further evaluation with imaging demonstrated mediastinal lymphadenopathy and only postoperative changes on brain MRI. In October 2002 the patient was enrolled on a clinical trial with EPO906A, an experimental epothilone.

Figure 1: Patient's Own Drawing of His Visual Symptoms
Patient's Own Drawing of His Visual Symptoms

The patient’s short-term memory improved after treatment of the intracranial metastasis, but his visual complaints of flashing lights and floaters persisted. There was no improvement with systemic steroids. In December 2002, a retinal specialist evaluated him. At that time, the patient reported a bright yellow-white light that moved in and out of visual fields and faded within seconds. (Figure 1). Moth-eaten visual fields and an essential normal retinal exam were documented ­(Figures 2 through 4). Visual acuity was intact with 20/30 OD (oculus dexter, or right eye) and 20/40 OS (oculus sinister, or left eye). An electroretinogram revealed a marked loss of b-wave amplitude, pathognomonic for melanoma-associated retinopathy (Figure 5).

Figure 2: Right Eye Visual Field
Right Eye Visual Field
Figure 3: Left Eye Visual Field
Left Eye Visual Field
Figure 4: Funduscopic Exam
Funduscopic Exam

The patient was initiated on intravenous immunoglobulin (IVIg) monthly with stabilization and eventual improvement/resolution of his visual symptoms. He tolerated EPO906A very well and had a complete response to treatment with resolution of the mediastinal lymphadenopathy. The drug was eventually discontinued after 12 months of treatment. The IVIg is still required monthly. We have been unable to discontinue the IVIg, as his vision deteriorates with attempts to taper the dose or increase the treatment interval. He is currently still being followed by the multidisplinary team and shows no evidence of melanoma.


Ophthalmology Review

Dr. Ragini Kudchadkar: Dr. Kimura, can you please review for us the ocular findings of melanoma-associated retinopathy (MAR)?

Dr. Alan Kimura: Patients with MAR often provide a history of photopsias and shimmering patches of color, and in this case shimmering yellow lights, the reappearance of which is a marker for too long an interval between IVIg treatments. Visual acuity is typically fairly well preserved. The largest review of patients with MAR documented a visual acuity of better then 20/60 in greater than 80% of patients.[1] Visual fields, however, are typically affected. Our patient showed constriction in visual fields with central scotomas. Though this type of presentation is common, there are many reports of patients with MAR that have normal visual fields. Thus, there are no specific visual field findings in MAR.

Funduscopic exam is generally normal in these patients. The largest series of patients in the literature demonstrates that approximately half have an essentially normal funduscopic exam.[1] In our patient, funduscopic exam was essentially within normal limits; however, occasional window defects were noted. These are not of clear significance. Other funduscopic findings that have been documented in the literature are optic nerve pallor, vessel attenuation, retinal pigment epithelium changes, and vitreous cells, although these finding are more characteristic of cancer-associated retinopathy (CAR), a paraneoplastic disease with autoantibodies directed against recoverin, a critical moiety of the visual cycle found in the photoreceptor.

Vitreous fluid analysis is only documented in a few patients with MAR. Among those patients (n = 10), most do show some cells with varying degrees of inflammation.[1] Melanoma cells are rarely seen, with only four documented cases throughout the literature.

Figure 5: Electroretinogram

The most important clinical diagnostic test is the electroretinogram (ERG). ERG is a measure of the electrical response of the retina to varying stimuli of light, under dark-adapted, then light-adapted states. The a-wave represents photoreceptor function, and the b-wave represents inner retinal function, reflecting either Mller cell or bipolar cell function. The classic finding of MAR, as demonstrated by our patient (Figure 5), is the so-called “negative ERG” featuring a low b/a-wave ratio in the “maximal, combined rod and cone response.” This is seen with a markedly reduced b-wave and a normal dark-adapted a-wave, which in the right clinical scenario is pathognomonic for MAR. The loss of the b-wave is due to an autoimmune response involving antigens located within the bipolar layer. Selective b-wave loss on ERG is also seen in congenital stationary night blindness, and a number of other inherited and noninherited toxic states (Table 1).


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