On this day in medical history: Dr. Cushing’s most baffling case

On this day in medical history, February 21, pioneering neurosurgeon Harvey Cushing, MD, performed the first of three brain surgeries on what he described as his “most baffling problem”—the case of Mary D.’s “interpeduncular cyst.”

Dr. Cushing, regarded as the father of American neurosurgery, left a legacy of clinical discoveries and surgical innovations. Among his many accomplishments, Dr. Cushing introduced blood pressure measurement and local anesthesia to the United States, and was a pioneer in using X-rays to diagnose brain tumors. He won the Pulitzer Prize for his two-volume biography of Sir William Osler. And, of course, he was the first to describe the endocrine disorder named after him, Cushing’s syndrome.

But at the start of the 20th century, Dr. Cushing was an intrepid, energetic young doctor who was just beginning his life’s calling as a brain surgeon.

Mary D.’s mysterious malady

In December 1901, Mary D., a 16-year-old seamstress, presented to Johns Hopkins Hospital in Baltimore, MD, with complaints of back pain, dizziness, and headache. She was overweight and physically and mentally underdeveloped (adiposogenital dystrophy). She reported failing eyesight with “dark spots” clouding her sight. Vision testing revealed a suspicious blurring of the nasal half of the visual fields.

She was followed closely until mid-February, when her visual fields suddenly narrowed. Ophthalmoscopic examination revealed mild pallor of the optic nerves with low-degree optic disc edema, suggesting an intracranial mass. She was transferred to the surgical ward.

On February 21, 1902, Dr. Cushing performed his first procedure on Mary D., an exploratory frontoparietotemporal craniotomy of the left hemisphere, which revealed hydrocephalus. A month later, he performed the same procedure on the right hemisphere, which resulted in almost complete resolution of the optic disc edema.

But a few days later she developed symptoms of ataxia, which led Dr. Cushing to perform a third operation, a suboccipital craniectomy and an exposure of the cerebellum, which proved negative. Her condition worsened rapidly after this procedure. She fell into a coma and died 6 weeks later.

An autopsy finally revealed a golf-ball sized tumor in the infundibular space overlying the pituitary body (the gland was found to be anatomically intact). The head pathologist classified the tumor as a teratoma, containing a mixture of cartilage, bone cells, myxomatous tissue, and other types of tissue cells.

The most baffling problem

At the same time that Dr. Cushing was puzzling over Mary D.’s case in Baltimore, Alfred Fröhlich, MD, in Vienna, Austria, published an account of a 14-year-old boy with an extraordinarily similar presentation. In a fortuitous twist of fate, the two doctors had met and worked together the previous summer in Liverpool, England.

In his paper, Dr. Fröhlich described his patient’s symptoms as a new syndrome (later dubbed Fröhlich’s syndrome) linked to a rare type of tumor involving the pituitary gland.

Dr. Cushing didn’t learn of Dr. Fröhlich’s report until after Mary D.’s death. But upon reading it, Dr. Cushing requested a histologic reanalysis of Mary D.’s “teratoma,” only to learn that the pathology department had somehow lost it.

Dr. Cushing was furious. From that day on, he demanded that he himself should keep all clinical charts and specimens removed from his patients. Thus, Mary D.’s case eventually yielded what is now the Cushing Brain Tumor Registry, a collection of about 500 brain specimens and thousands of records, currently on display at Yale University Medical Library, New Haven, CT.

For the rest of his career, Dr. Cushing repeatedly attempted to accomplish an effective surgical approach for the type of “interpeduncular cyst” (which was likely an adamantinomatous craniopharyngioma) he had first encountered in Mary D.’s case.

“All in all, these cases offer the most baffling problem which confronts the neurosurgeon,” Dr. Cushing later noted.

Although Mary D.’s case itself was unsuccessful, it was the catalyst that led Dr. Cushing to a lifelong and productive pursuit of knowledge about the pituitary gland and its influence on human growth and development.