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The first detailed medical descriptions of skin diseases can be found in the medical literature at the end of the 18th century, when scientists started to use the concept of the skin as an organ. Before that time, it made no sense to describe details of skin changes as we do today, since they were thought to be only signs of an uneven distribution of internal body fluids. These disturbances could much better be diagnosed by examination of urine.
Giovanni Battista Morgagni (1682-1771) postulated the importance of tissue and organs. One of the first books of skin diseases regarding the skin as an organ was written by Anne Charles Lorry (1726-1783) in 1776. He also described tumors [''Fleischgewachse (Sarcome)''] that develop in the skin, grow, multiply, and fester. It is not possible to make a clear retrospective diagnosis of these lesions.
In 1806, Alibert (1768-1837) presented an extraordinary skin disease which he described in detail under the name of "Pian fungoides'' in 1814 and as "Mycosis fun-goides'' in 1832 in his second volume of "Monographie des Dermatoses." He called this "a strange disorder of the skin with mushroom-like tumors'' (1,2). The case he observed was a patient named Lucas. The disease began with a desquamating rash ("eruption furfuracee''). Lucas died 5 years later of illness with numerous tumors on his face and body.
With the clinical symptoms Alibert described and looking at the figure published in 1832 (Fig. 1), we would still diagnose the disease as mycosis fungoides.
In the atlas mentioned above, there is also the famous illustration of the "Arbre des Dermatoses'' showing the classification of skin diseases Alibert created (Fig. 2). In this tree, we can find mycosis fungoides in the branch of the venerous diseases, as in the opinion of Alibert, it was a European form of the tropical disease "smallpox of Amboyna'' or ''pian ruboide'' or yaws (Fig. 3).
The tropical disease "smallpox of Amboyna'' had been described by Bontius (1592-1631) (3) (Fig. 4). Bontius identified the difference between this disease and
syphilis (e.g., that it is not transmitted by sexual intercourse). After the death of Bontius, his notes had been published in 1658 by Gulielmo Piso in six books of his work ''de Indiae utriusque re naturali et medica'' (Fig. 5). It is worth noting that Alibert in 1832 copied part of the text from Bontius word by word.
Although he gave the disease the name, it would be a mistake to say that Alibert was the first to describe a lymphoma of the skin, for at this time the etiology of the disease was completely unclear, neither were the characteristics of cancer defined nor was there a theory of cells as components of the body structure. White blood cells had not yet been discovered. Still believing that the atmosphere played an important role in the genesis of most diseases, Alibert was astonished that his patient in Paris got the disease in a climate that was much milder than that of Indonesia.
In the following decades, Alibert's description of mycosis fungoides has been discussed by many different authors and has often been compared with or used as a synonym for ''Molluscum of Bateman,'' a disease Thomas Bateman (1778-1821) published which we can today diagnose as neurofibromatosis.
Another step towards the establishment of lymphomas of the skin was taken when it was recognized that the tumors represented an alteration of lymphocytes. The development of new staining techniques with some highly specialized stains made it possible to categorize the lymphomas. During the second half of the 19th century, the main emphasis was on observing skin biopsies and interpreting skin changes with the knowledge gained from histological changes.
In 1864, Heinrich Kobner (1838-1904) published the first histological description of a lymphoma of the skin and called it ''beerenschwammahnliches Papillar-geschwulst der Haut'' (sponge-like papillary tumor of the skin). Along with many contemporaries, he assigned them to the "Granulationsgeschwiilste" which develop as a response to some unknown agent. In 1845, Rudolf Virchow (1821-1902), one of the most famous advocates of the cell theory, created the term "lymphoma" for a group of tumors with structures similar to the lymphatic tissue, such as the intestinal follicles. Lymphoma was used to describe a tumor of lymphatic cells without differentiating between malignant proliferations and inflammatory hyperplasia. In his lectures, Virchow mentions the work of Kobner but still felt that mycosis fungoides was not a lymphoid disease but rather similar to yaws.
The first connections of mycosis fungoides with the lymphoid system were made in 1869. The microscopic studies of Xavier Gillot and Louis Antoine Ranvier (1835-1922) in Paris indicated that mycosis fungoides was caused by regeneration of lymphoid tissue in the skin. They considered mycosis fungoides as a cutaneous manifestation of lymphoma—called lymphadenie cutanee (4). It was Gillot who in his thesis was the first to describe different clinical stages of mycosis fungoides. He assigned the symptoms to four stages:
Taches congestives (erythematous stage: itching and red colored patches)
Plaques lichenoides (lichenoid stage: itching and different plaques with small papules)
Tumeurs fongoides (fungal stage: mushroom-like tumors of different size)
Ulcerations et cicatrices (the tumors are breaking up)
Ernest Bazin (1807-1878) published his three different stages one year later than Gillot. Nevertheless, he is today regarded as the original describer of the clinical stages of mycosis fungoides (5):
Periode erythemateuse (erythematous stage: red colored patches)
Periode lichenoide (the lichenoid stage: itching and different plaques with small papules)
Periode fongoidique, mycositique (fungal stage: mushroom-like tumors of different size)
A second type of mycosis fungoides was found in 1885 by Emile Vidal (1825-1893) and Jean-Louis Brocq (1856-1928). They published a review of six cases as ''Etude sur le mycosis fungoides.'' Their cases III, V, and VI corresponded to the stages of Bazin. But cases I, II, and VI were missing the typical initial stages. The disease started directly with tumors and its course was rapid and fatal. This type was called mycosis fungoides d'emblee.
In 1892, Frangois Hensi Hallopeau (1842-1919) and Ernest Besnier (1831-1909) wrote about a third variant of mycosis fungoides: the erythroderma type
(6). All of the six cases they had observed began with a reddish rash over the entire body. They denied a connection to leukemia. It was Albert Franz Sezary (1880-1956) who at a meeting of the French Society of Dermatology and Syphiligra-phy in February 1938 presented a patient with an erythroderma "avec presence de cellules monstrueuses dans le derme et le sang circulant'' (with monstrous cells in the skin and circulating blood) as a leukemic variant of a reticulosis (cancer of lymphatic cells) of the skin—this disease nowadays still bears his name as an eponym
The development of electron microscopy finally made it possible for Lutzner to describe the cells in Sezary syndrome with their cerebriform nuclei in detail. They are known today as ''Lutzner cells'' (8). In the following years, many research groups used electron microscopy, cytophotometry, and cytogenetics to search for connections of the different clinical aspects and diseases such as Sezary syndrome and mycosis fungoides. In 1975, Lutzner and others confirmed that they could be classified as entities in the spectrum of cutaneous T-cell lymphomas (9).
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