Rare Disorder Reveals Interplay of Cancers And Body's Defenses
By NATALIE ANGIER
Published: September 17, 1991
WHEN the 50-year-old woman first went to see Dr. John E. Greenlee, she could hardly speak an intelligible word, and her jaw did not stay still: it jerked open and shut and from side to side, clacking and chattering like a puppet's mouth gone amok.
Her eyes rolled round and round in their sockets, unable to focus on anything, and the movement of her limbs was wildly uncoordinated. If she reached for anything, her hand either swung way past the object or knocked it over clumsily.
A month later, she could not walk, but lying down was no better. Her body jittering and flailing in all directions, she looked like a mental patient on nonstop electroshock therapy.
"She was totally incapacitated," said Dr. Greenlee, a professor of neurology at the University of Utah in Salt Lake City. "The level of neurological damage was extraordinary."
Half a year later, the woman was dead, killed by an ovarian tumor that in a roundabout way had set off the neural devastation in the first place. Rare and Devastating
The woman suffered from neurological paraneoplastic syndrome, a rare and bizarre disorder that accompanies a small percentage of cases of cancers of the ovaries, uterus, breast and lung.
The syndrome is not the result of spreading cancer cells, but rather an autoimmune response: a perverse byproduct of the body's campaign to heal itself. Rallied to help stifle a nascent malignancy, the immune system at the same time begins destroying the healthy cells of the brain and other parts of the nervous system.
Until very recently, the puzzling syndrome was almost completely unknown outside neurology circles, and as a result was often misdiagnosed, as multiple sclerosis, meningitis or even alcohol-induced dementia.
But in a rush of discoveries, researchers have begun to understand precisely what causes the syndrome, and they are using their insights to better understand the subtle interplay between the immune system and cancer.
They have identified the components of the nervous system that are the mistaken targets of the body's battle against cancer, and they are learning why gynecological and lung tumors are the likeliest to set off an autoimmune response against nerve tissue. Tests Detect Disorder
Dr. Jerome B. Posner of Memorial Sloan-Kettering Cancer Center in New York, a pioneer in the study of paraneoplastic syndrome, and his colleagues have devised simple antibody tests that can detect some types of aberrant immune reaction as easily as clinicians now pick up thyroid disease.
The new discoveries are spurring physicians of all persuasions to take heed of paraneoplastic syndrome, and that awareness can make a considerable difference for patients. The neurological symptoms often appear long before a person is aware of having cancer, or indeed before evidence of a tumor shows up on an X-ray or any other standard test. In some instances, the same immune cells that are erroneously assaulting the nervous system seem to be especially effective at keeping the tumor in check.
After proving with an antibody test that a patient's neurological disorder is the sign of an underlying tumor, the physician can then proceed to hunt down the malignancy and root it out as quickly as possible.
More fundamentally, the new research offers an unusual opportunity to explore how the body discriminates between tumor cells and its own healthy cells, and why that process sometimes goes awry.
"We've got a unique window onto the immunobiology of human cancer in these patients," said Dr. Vanda A. Lennon, the director of the neuroimmunology laboratory at the Mayo Clinic in Rochester, Minn. "I consider paraneoplastic syndrome to be the first unambiguous evidence that the human immune system can respond to tumors."
Researchers also expect that as they explore paraneoplastic disease more thoroughly, they will find many variations on the autoimmunity theme. Uncertainty on Incidence
By current estimates, fewer than 1 percent of patients with gynecological and small-cell lung cancers suffer from paraneoplastic syndrome, and only 100 to 200 new cases of the disorder are firmly diagnosed each year in the United States, but most in the field believe many cases are overlooked.
"I think we're only seeing the tip of the iceberg," said Dr. Lennon. "I think paraneoplastic syndromes will prove to be uncommon, but not as rare as the textbooks say they are."
Doctors have known since the beginning of this century that some cancers can have an ancillary effect on the nervous system, and the syndromes were given the name paraneoplasia, after "para," for beside or next to, and "neoplasia," a new growth or malignancy.
But until recently the syndromes were suspected to be the result of, for example, the release of toxic hormones by the tumor cells.
With the development of advanced methods for identifying antibodies and antigens, the components of cells hat antibodies recognize and latch onto, researchers have learned that the cause of paraneoplastic syndrome is an unfortunate resemblance between proteins on tumor cells that prompt an immune attack and proteins on healthy neurons.