Paraneoplastic Presentations of Testicular Cancer — Clinical and Immunological C
August 1, 1999 3 minutes read
Paraneoplastic Presentations of Testicular Cancer—Clinical and Immunological Characterization
Abstracts & Commentary
Sources: Voltz R, et al. A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med 1999;340:1788-1795; Dalmau J, et al. Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 1999;122:27-39; Bennett JL, et al. Neuro-ophthalmologic manifestations of a paraneoplastic syndrome and testicular carcinoma. Neurology 1999;52:864-867.
In this study by voltz and colleagues, 13 testic-ular cancer patients with a syndrome of limbic and brainstem encephalitis were tested for the presence of serum antineuronal antibodies. Ten of these patients (ages 26-45) had antibody positive sera against a 40-kd protein, which were then used to identify a cDNA clone (termed Ma2) from a recombinant brain library. The expression of Ma2 is normally highly restricted to the brain and testis (2 immunologically isolated organs that do not typically express MHC antigens), and is likely to be a phosphoprotein.
The study by Dalmau and colleagues describes a related neuronal protein (Ma1) that was characterized with antibodies from four patients’ sera with other tumor types (parotid, breast, colon, and large cell lung cancer) and a paraneoplastic limbic encephalitis. Three patients had brainstem and cerebellar dysfunction, and one had dysphagia and motor weakness.
In a detailed report of two cases by Bennett and associates, the patients, ages 28 and 30, presented with supranuclear gaze disorders and limbic encephalitis associated with testicular cancer. One patient had confusion, somnolence, visual and auditory hallucinations, and a vertical gaze palsy. The second had vertical diplopia that progressed to oscillopsia with dysarthria and ataxia.
Commentary
In these three related papers by investigators at Memorial Sloan Kettering Cancer Center, a growing family of paraneoplastic antigens is further defined. Their findings have importance for clinical practice, beyond the excellent clinical characterization of this syndrome; in eight of the 10 patients studied by Voltz et al, the neurologic symptoms and signs preceded the diagnosis of testicular cancer. Thus, in male patients presenting with a limbic and brainstem encephalitis, an underlying malignancy may be diagnosed at an earlier and potentially more curable stage. The serum assay for Ma1/Ma2 is now offered as a commercial test by Athena Diagnostics (800-394-4493).
Even with apparent resection of testicular cancer, however, the neurological disorder often does not improve even with plasmapheresis or IVIG. This refractory disease process may reflect, in part, irreversible neuronal loss and gliosis, in addition to an activated T- and B-cell population directed against the Ma1 and Ma2 brain antigens. At present, our ability to diagnosis paraneoplastic diseases surpasses our ability to treat them. Although uncommon, a paraneoplastic disorder should be considered in certain patients with limbic and brainstem encephalitis not related to infection or toxic-metabolic causes. —ba
Which of the following statements is incorrect?
a. Paraneoplastic limbic encephalitis usually precedes the diagnosis of cancer.
b. Paraneoplastic limbic encephalitis is only seen with testicular cancer.
c. The brain protein Ma2 is also found in the testis.
d. Plasmapheresis has not been an effective therapy in paraneoplastic limbic encephalitis.
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