Adrenocortical carcinoma in a 17th-century girl.

Adrenocortical carcinoma (ACC) is a rare, often fatal disease, that may be seen sporadically or with hereditary predisposition syndromes. Patients with ACC are usually girls under the age of seven who present signs of excess production of adrenal glucocorticoids and androgens, with the diagnosis being confirmed by imaging. Here we reproduce and examine what we believe to be the first autopsy case report of a child with ACC, reported by Dr. Henry Sampson in Philosophical Transactions, published by The Royal Society of London in 1697. The paper describes the autopsy of a girl with severe virilization and profound signs of Cushing syndrome who died at age six, strongly suggesting ACC. She apparently had extensive pulmonary metastases, and may have had liver involvement. The report indicates her disease arose from her left kidney and there is no indication of an adrenal origin, perhaps because the adrenal gland was not generally known as a separate organ at that time. This classic example of an early case report is particularly instructive in the context of medical knowledge and understanding in the 17th century compared to current knowledge.

Pathology of the adrenal cortex: a reappraisal of the past 25 years focusing on adrenal cortical tumors.

A reappraisal of the major advances in the diagnostic pathology of adrenal cortical lesions and tumors in the last 25 years is presented, with special reference to the definition of malignancy in primary adrenal cancer and its variants. Slightly more than 25 years ago, Weiss proposed his diagnostic scoring system for adrenal cortical carcinoma. This represented a milestone for adrenal pathologists and the starting point for further modifications of the system, either through minor changes in the scoring procedure itself or concentrating on some particular Weiss criterion such as mitotic index, integrated into alternative scoring schemes or algorithms that are currently under validation. Improvements in diagnostic immunohistochemistry have led to the identification of markers of cortical origin, such as Melan-A, alpha-inhibin, and SF-1 and of prognostic factors in carcinoma, such as the Ki-67 proliferation index and SF-1 itself. With regard to hyperplastic conditions, genetic investigations have allowed the association of the majority of cases of primary pigmented nodular adrenocortical disease (PPNAD) in Carney complex to mutations in the gene encoding the regulatory subunit 1A of protein kinase A (PRKAR1A). Other hereditary conditions are also associated with adrenal cortical tumors, including the Li-Fraumeni, Beckwith-Wiedemann, Gardner, multiple endocrine neoplasia type 1, and neurofibromatosis type 1 syndromes. Moreover, several advances have been made in the knowledge of the molecular background of sporadic tumors, and a number of molecules/genes are of particular interest as potential diagnostic and prognostic biomarkers.