The centennial of Bowen’s disease—a critical review on the occasion of the 100th anniversary of its original description

Some issues are extremely simple if looked at without prejudice. This is also true for carcinomas. Carcinomas are malignant neoplasms of epithelial cells. Where are they going to arise? In the epithelium. Therefore, at the outset, they must be confined to the epithelium. How are they going to look in the beginning? Small and inconspicuous. How are they going to develop? They will grow and unfold the capacities with which they are endowed unless they are destroyed. This is nothing special but true for every living matter. 
 
But unprejudiced reflection is difficult because we all adopt conceptions of our time that channel our thinking. For many centuries, carcinomas were never treated before they had metastasized. Recurrences were soon to occur, and most patients died shortly after seeking treatment. The incurability of cancer was so deeply rooted in the worldview of physicians that the diagnosis of cancer was always challenged when a patient survived. Because carcinomas were excised only in stages far advanced, the bulk of the tumor was present in the dermis or deeper structures. That circumstance prompted Rudolf Virchow in 1855 to suggest derivation of carcinomas from cells of connective tissue, a concept to which he adhered for many years afterward. In 1865, Carl Thiersch proved the epithelial origin of cancer, but he believed that the true reason for the epithelial proliferation was a pathological weakness of the connective tissue that enabled sprouts of epithelium to grow in. As late as in 1894, Hugo Ribbert averred that carcinomas did not result from growth of epithelium into connective tissue but from growth of connective tissue into the overlying epithelium [1].


Introduction
Clarke White at Massachusetts General Hospital. One year later, he was elected instructor in dermatology at the Harvard Medical School. Following White's retirement in 1902, Bowen was promoted to assistant professor, and in 1907 he became the first Wigglesworth Professor of Dermatology [2].
Bowen devoted himself especially to dermatopathology.
In cases that required histopathologic clarification, his expertise was sought. When White in 1889 gave the first precise description of dyskeratosis follicularis, Bowen provided the histopathologic part, described a "keratosis of the epithelial lining of the mouths of the follicles" with "scattered bodies of a concentric arrangement" and came to the correct conclusion that he was dealing with a disorder of cornification [3]. A few months later, the disease was described independently by Jean Darier of Paris who considered those "concentric bodies" to be parasites, so-called "psorosperms," and referred to the disease as "psorospermose folliculaire végétante." Bowen, however, after having studied additional biopsy specimens, insisted that the psorosperm-like bodies in the horny layer "undergo at least a partial keratosis, or, in other words, are subject to much the same changes that    in 1896 completely retracted his psorosperm theory and acknowledged that Bowen was right [4,5].
Most scientific contributions of Bowen had a distinct histologic or histopathologic focus. Some of them dealt exclusively with findings obtained by microscopy ( Figures   2-5), e.g., a study in 1889 about "The epitrichial layer of the skin" in which Bowen proposed the existence of a distinct epithelial layer on the surface of the skin of human embryos between the third and sixth month of gestation [6]. Others wedded clinical and histopathologic findings, including Bowen's study of the disease that came to bear his name. It was published in the Journal of Cutaneous Diseases in 1912 under the title "Precancerous dermatoses: a study of two cases of chronic atypical epithelial proliferation" [7].
Bowen by far preferred the microscope to seeing patients.
He was a member of several medical societies and in 1902 president of the American Dermatological Association, but he did not like public appearances. Lectures were almost a torture to him. He loved children, but he never married.
Though very sociable in his youth, he withdrew more and more into himself as life went on. Following his retirement in 1927, he read a lot and used to spend the summer months in Europe, especially in France. In those years, he began to suffer from vertigo that became worse steadily. Bowen died in Boston on December 3, 1940 [2].

History of the description of Bowen's disease
More than seventy years later, Bowen's name is still remembered by every student of medicine. That fact can be attributed chiefly to Jean Darier. The French pioneer of dermatopathology never met Bowen personally, but he had great esteem for his American colleague and suggested in 1914 that the disease described by Bowen be linked eponymically to his name [8]. Two years earlier, Bowen had detailed findings in two patients who presented with localized, irregular patches and plaques on the buttock and on the calf, respectively. The lesions measured about four inches in diameter.
Bowen described them as "only slightly elevated above the normal skin, of a moderately firm consistency, and dull red in color. The surface was in some places slightly crusted; in other places it had a papillomatous character. The lesions were in places confluent, forming areas of tumorlike masses; in other places, especially at the edge of the affected areas, they were discrete, or assumed annular or serpiginous figures. Apparently, the lesions never disappeared spontaneously" [7]. he considered the skin lesions to represent "long-persistent eczema, or psoriasis," and suggested "that a superficial disease induces in the structures beneath it, in the course of many months, such degeneracy as makes them apt to become the seats of cancer" [9].
In the subsequent years, carcinomas developing on preexisting "eczematous" lesions were also described at other sites, such as the scrotum (Crocker, 1888) or the glans penis (Pick, 1891). At the International Congress of Dermatology in London in 1896, William Dubreuilh of Bordeaux introduced the term "precanceroses" for solar keratoses ("keratoma senile"), arsenical keratoses, "cornu cutaneum," "leukokeratoses," and other epithelial lesions that commonly gave rise to carcinoma. In contrast to Paget, Dubreuilh recognized that the "pre-existing" lesions were not benign. He emphasized that "this is not a malignant transformation, as we are used to call it; this is simply an aggravation or acceleration of the process because one finds in these precanceroses the essential characteristics of the malignant tumor." Nonetheless, Dubreuilh refrained from calling the lesions malignant because they could "remain stationary indefinitely, they may also heal spontaneously" [10]. The fact that malignant neoplasms may grow extremely slowly, or apparently not at all, and that even widespread metastases may at times regress spontaneously, was beyond the horizon of physicians of that time.
For decades to come, intraepithelial malignancies were referred to as "precanceroses." One example was "erythroplasie du gland," described in 1911 by Louis Queyrat of Paris on the glans penis of four men. Because three of those great importance, are in reality of secondary nature . . . the day has passed when epithelium can be considered noncarcinomatous or at the most only precarcinomatous because it is within the confines of the so-called basement membrane and, conversely, carcinomatous because it has penetrated beyond this barrier. It is therefore imperative that the microscopist take into consideration the character of the epithelial cells above everything else in order to arrive at a correct diagnosis" [15].
It may seem curious that such truisms needed to be emphasized at all. However, only after Broders had coined the term "carcinoma in situ," the obvious came to be accepted, namely, that a malignant neoplasm of epithelial cells begins in the epithelium. It took many more decades until the fact was appreciated that "lentigo maligna" is a synonym for melanoma in situ occurring in sun-damaged skin, and "Bowen's disease" a synonym for a particular type of carcinoma in situ characterized by scatter of markedly atypical epithelial cells in all reaches of the epidermis.
The importance of referring to lesions by an unambiguous name that reflects their true biologic behavior could not be illustrated more emphatically than by reviewing the original articles of 1912. Dubreuilh suggested refraining from treatment of the "circumscribed precancerous melanosis," arguing that, "to me, the surgical operation does not seem to be justified in regard to the pure melanosis because its malignant transformation is uncertain" [14]. John Templeton Bowen treated lesions of his patients with various techniques but never strove for eradicating them completely. This was reflected by the outcome: "New lesions slowly grew at the periphery of the areas that had been treated by the curette or by freezing, and there were apparently some recurrences in the cicatrix or within its boundaries" [7]. Had Dubreuilh and Bowen appreciated fully the malignant nature of the neoplasms they described, they would have been in a far better position to manage their patients.

Resurgence of Bowen's problems of interpretation in modern pathology
of patients. What is an "intraepithelial neoplasia"? Benign or malignant? Does an epithelial tumor with markedly atypical nuclei and myriad mitoses really become malignant only after its first cells have traversed the basement membrane? And can early "invasion" be recognized consistently? Is it not the "character of the epithelial cells" that must be taken into consideration "above every else in order to arrive at a correct diagnosis"? In recent years, the simple logic of Albert C.
Broders has been suspended in some realms of medicine, and physicians once again find themselves in the same position as John Templeton Bowen 100 years ago.