The first description of carcinoid tumors dates back to the 19th century, when Merling (1808), Langhans (1867), and Beger (1882) identified appendiceal carcinoids as a unique histologic entity. Lubarsh described multicentric small tumors in the small intestine originating from the intestinal glands (Lieberkiihn).7 In 1907 Oberndorfer for the first time used the term carcinoid to define the tumors as benign and carcinoma-like.8 Between 1914 and 1928 Masson described special staining techniques with silver impregnation (Grimelius), which showed the carcinoid tumor cells to be argentaffin.9'10 Thus, these tumors were attributed to the enterochromaffin cells named after Kulchitsky and were postulated to be of endocrine origin.11 In 1938 Feyrter, a German pathologist, described special cells and their morphologic similarity to other neuroendocrine cells and defined the diffuse endocrine system distributed throughout the body.12 In 1953 serotonin was identified as the characteristic product of the carcinoid tumors. In 1954, Thorson, coincidentally with Cassidy, Bjorck, Isler, Hedinger, and Waldenstrom, defined the "carcinoid syndrome" with the typical symptoms of flushing, diarrhea, and valvular heart disease.

Williams and Sandler classified carcinoid tumors according to their distribution in the foregut, midgut, and hindgut.13 In 1969 Pearse included carcinoid tumors in the amine precursor uptake and. decarboxylation (APUD) system.1415 However, their presumed common origin from the neural crest holds true only for some of these cells.1617 In 1984, Falkmer characterized carcinoid tumors by immunohisto-chemistry, showing a specific pattern of neurohormonal peptides. It has become apparent, however, that the general term carcinoid fails to describe the diverse spectrum of neoplasms with regard to functional state, localization, growth pattern, degree of differentiation, expression of different neuroendocrine marker molecules, and prognosis. A new classification emerged in 1995 that includes not only the site of origin but also variations in the histologic characteristics of carcinoid tumors (Table 86-1).418 Using this system, carcinoid tumors are classified as well-differentiated neuroendocrine tumors and well-differentiated (low-grade) and poorly differentiated (high-grade) neuroendocrine carcinomas. The term carcinoid tumor should preferably be used for classical midgut carcinoids, whereas other types of carcinoids should be termed neuroendocrine tumor followed by their primary location, for example, neuroendocrine thymic, gastric, small bowel, or rectal tumor.

TABLE 86-1 History of Carcinoid Tumors



Lubarsch (1888)

Identified small multicentric


Oberndorfer (1907)

Introduced the term carcinoid

Masson (1914-1928)

Presented silver staining of

enterochromaffin cells,

endocrine origin

Feyrter (1938)

Identified diffuse neuroendocrine


Lembeck (1953)

Investigated serotonin production

Thorson (1954)

Identified carcinoid syndrome

Williams (1963)

Introduced classification; foregut,

midgut, hindgut

Pearse (1969)

Introduced the APUD system

Falkmer (1984)

Presented state-of-the-art data:

IHC pattern of neurohormonal


Capella (1995)

Revised classification

APUD = amine precursor uptake and decarboxylation;

HC = immunohistocliemistry.

Rights were not granted to include this figure in electronic media Please refer to the printed publication

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