Harvey Cushing and pituitary Case Number 3 (Mary D.): the origin of this most baffling problem in neurosurgery

From the very beginning of his career, Harvey Williams Cushing (1869-1939) harbored a deep interest in a complex group of neoplasms that usually developed at the infundibulum. These were initially known as interpeduncular or suprasellar cysts. Cushing introduced the term craniopharyngioma for these lesions, which he believed represented one of the most baffling problems faced by neurosurgeons. The patient who most influenced Cushing's thinking was a 16-year-old seamstress named Mary D., whom he attended in December 1901, exactly the same month that Alfred Frohlich published his seminal article describing an adiposogenital syndrome in a young boy with a pituitary cyst. Both Cushing's and Frohlich's patients showed similar symptoms caused by the same type of tumor. Notably, Cushing and Frohlich had met one another and became good friends in Liverpool the summer before these events took place. Their fortunate relationship led Cushing to realize that Frohlich's syndrome represented a state of hypopituitarism and provided a useful method of diagnosing interpeduncular cysts. It is noteworthy that Cushing's very first neurosurgical procedure on a pituitary tumor was performed in the case of Mary D.'s interpeduncular cyst, on February 21, 1902. Cushing failed to remove this lesion, which was later found during the patient's autopsy. This case was documented as Pituitary Case Number 3 in Cushing's masterpiece, The Pituitary Body and Its Disorders, published in 1912. This tumor was considered a teratoma; however, multiple sources of evidence suggest that this lesion actually corresponded to an adamantinomatous craniopharyngioma. Unfortunately, the pathological specimens of this lesion were misplaced, and this prompted Cushing's decision to retain all specimens and documents of the cases he would operate on throughout his career. Accordingly, Mary D.'s case crystallized the genesis of the Cushing Brain Tumor Registry, one of Cushing's major legacies to neurosurgery. In this paper the authors analyze the case of Mary D. and the great influence it had on Cushing's conceptions of the pituitary gland and its afflictions, and on the history of pituitary surgery.