Diagnosis of occult melanoma using transient receptor potential melastatin 1 (TRPM1) autoantibody testing: a novel approach.
OBJECTIVE
To report the first case of melanoma-associated retinopathy (MAR) and underlying occult melanoma diagnosed based on the presence of serum transient receptor potential melastatin 1 (TRPM1) autoantibodies.


METHODS
Interventional case report with basic science correlation.


METHODS
One patient with MAR.


METHODS
Testing for the presence of serum TRPM1 autoantibodies.


METHODS
Diagnosis of an occult melanoma involving the axillary lymph nodes (unknown primary site) and MAR based on the presence of TRPM1 autoantibodies in the patient's serum.


RESULTS
The patient's clinical exam was remarkable for mild intraocular inflammation in both eyes and retinal hemorrhages with an apparent choroidal neovascularization in the left eye, which was confirmed by fluorescein angiography and indocyanine green angiography testing. Humphrey visual field 30-2 SITA-fast (Humphrey Visual Field Analyzer, Carl Zeiss Meditec, Inc, Dublin, CA) demonstrated diffuse depression in both eyes out of proportion to the clinical exams, prompting electroretinography testing that revealed an electronegative response. Dark-adapted thresholds were markedly elevated and mediated by cones. Due to concern for MAR, a systemic work-up for melanoma was performed by the primary care physician that was unrevealing. Given our continued clinical suspicion for MAR, the patient's serum was sent for evaluation for TRPM1 autoantibodies. The patient's serum applied to normal human retina exhibited positivity in the inner nuclear layer. Application of the patient's serum to wild-type and TRPM1 knockout mouse retina revealed strongly labeled bipolar cells in the wild-type retina, but not in the TRPM1 knockout retina, indicating TRPM1-dependent immunoreactivity. The antigen was confirmed as TRPM1 by labeling of TRPM1-transfected human embryonic kidney 293 cells. Additional systemic work-up prompted by this finding resulted in identification of an occult metastatic melanoma involving the axillary lymph nodes with an unknown primary site. The patient underwent surgical excision of the occult melanoma without evidence of other sites of metastases. He also received intravenous immunoglobulin therapy and his vision has stabilized.


CONCLUSIONS
This is the first reported case of a melanoma-associated retinopathy diagnosed utilizing the innovative approach of testing for serum TRPM1 autoantibodies.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Monica D
MD
Dalal
Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon.
Catherine W
CW
Morgans
Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon.
Robert M
RM
Duvoisin
Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon.
Elizabeth A
EA
Gamboa
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Brett G
BG
Jeffrey
Mid Atlantic Retina, The Retina Service of Wills Eye Institute, Philadelphia, Pennsylvania.
Sunir J
SJ
Garg
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Chi-Chao
CC
Chan
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: senh@nei.nih.gov.
H Nida
HN
Sen
D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D001365:Axilla; D015415:Biomarkers; D004596:Electroretinography; D005451:Fluorescein Angiography; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000556:secondary*; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000473:pathology*; D059545:Paraneoplastic Syndromes, Ocular / Q000175:diagnosis* / Q000276:immunology; D051245:Retinal Bipolar Cells / Q000473:pathology; D050053:TRPM Cation Channels / Q000276:immunology*; D058609:Visual Field Tests
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human