Perspectives in Pathology
Siegfried Oberndorfer: Origins and
Perspectives of Carcinoid Tumors
IRVIN M. MODLIN, MD, P
H
D, FACS, MICHAEL D. SHAPIRO, BS,
AND MARK KIDD, P
H
D
Carcinoid tumors are rare, indolent neoplasms that, although
clinically well defined, are regarded as exotic and are consequently
often unrecognized. Although little is known of the lives of the men
who defined the tumor, described its distinct histology and cell type,
and delineated the clinical hallmarks of the disease even less is known
of the pathobiology of the lesion. In the nineteenth century, T.
Langhans (1839-1915), O. Lubarsch (1860-1933), and W. B. Ransom
(1860-1909) described unusual tumors in the small bowel but each
failed to adequately investigate these novel entities. This responsibil-
ity fell to Siegfried Oberndorfer (1876-1944), who became the first to
adequately characterize the nature of the tumors and refer to them as
“benign carcinomas.” During his tenure at the Pathological Institute
of the University of Munich, Oberndorfer noted in 1907 that the
lesions were distinct clinical entities and named them “karzinoide”
(“carcinoma-like”), emphasizing in particular their benign features.
In 1929 he amended his classification to include the possibility that
these small bowel tumors could be malignant and also metastasize.
Although the enterochromaffin cell, the carcinoid cell of origin, had
been identified as early as 1897 by N. Kulchitsky (1856-1925), it was
not until 1953 that F. Lembeck (1922–) established that such cells
synthesized and secreted serotonin—a potent bioactive amine. There-
after the protean clinical effects of serotonin, including “flushing,”
were recognized as was the associated relationship of carcinoid heart
disease (Bio¨rck in 1952) and fibrosis (Moertel in 1961). As the
centennial of the observations of Oberndorfer approaches, it should
be noted that the legacy of one of Germany’s most distinguished
pathologists, teachers, and scientists (whose career fell victim to the
machinations of the Third Reich) has been largely unrecognized.
Similarly, the biology and mechanistic analysis of these lesions remain
to a large extent unexplored. The present article describes the con-
tributions of the clinical and scientific pioneers in the elucidation of
carcinoid disease and traces the evolution of the discovery and un-
derstanding of carcinoid tumor biology. It also serves to memorialize
the extraordinary accomplishments of Oberndorfer, whose vision
exceeded his times. H
UM
P
ATHOL
35:1440-1451. © 2004 Elsevier Inc.
All rights reserved.
Key words: carcinoid, chromogranin A, neuroendocrine, Obern-
dorfer, serotonin.
Abbreviations: 5-HT, 5-hydroxytryptamine; 5-HTP, 5-hydroxytry-
tophan; APUD, amine precursor uptake and decarboxylation; DNES,
diffuse neuroendocrine system; EC, enterochromaffin; ECL,
enterochromaffin-like.
Carcinoid tumors are usually relatively slow-grow-
ing, indolent neuroendocrine neoplasms that some-
times behave in a highly malignant fashion, exhibiting
profuse metastatic behavior, most often to the liver and
lungs. They are the most common primary neoplasm of
the small bowel. Tumors usually present with flushing,
diarrhea, liver metastases, or small bowel obstruction,
due usually to peritumoral peritoneal fibrosis. Indeed,
the diagnosis of carcinoid lesions is often an incidental
finding in patients undergoing laparotomy or small
bowel resection for intestinal bleeding, obstruction, or
inexplicable perforation. Some patients present with
the classical carcinoid syndrome, characterized by
flushing, diarrhea, bronchoconstriction, and edema, or
exhibit carcinoid heart disease, most commonly pre-
senting as right-sided heart failure caused by subendo-
cardial valvular fibrosis.
Even with ever-increasing recognition and under-
standing of carcinoid tumors,
1
the memory of the pa-
thologist who first described this clinical entity has
faded into near obscurity. Siegfried Oberndorfer was a
pioneer in the field of carcinoid tumor biology, and his
early scientific contributions to the elucidation of car-
cinoid tumors provided the foundation of the disease
process.
SIEGFRIED OBERNDORFER
Siegfried Oberndorfer was born in Munich, Ger-
many on June 24, 1876, the second son of successful
real estate buyers in the Altstadt, the older part of
Munich. He spent his youth in Munich and obtained
his medical degree from the University of Munich in
1900. Oberndorfer initially demonstrated his interest in
pathology while spending a term of medical school in
Kiel (1898), where he studied with his first pathology
mentor, A. Heller (1840-1913). He cultivated this inter-
est by serving as an assistant at the Pathological Institute
of the University of Munich from 1902 to 1906, where
he was further influenced by his coassistant, Hermann
Du¨rck (1869-1941). In 1906, Oberndorfer made his
first significant contribution to the field of pathology, a
study of chronic appendicitis,
2
and was also appointed
as Lecturer of Pathological Anatomy at the Munich
From the Gastric Pathobiology Research Group, Department of
Surgery, Yale University School of Medicine, New Haven, CT. Ac-
cepted for publication September 15, 2004.
Address correspondence and reprint requests to Irvin M. Mod-
lin, MD, P
H
D, FACS, Yale University School of Medicine, 333 Cedar
Street, P.O. Box 208062, New Haven, CT 06520-8062.
0046-8177/$—see front matter
© 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.humpath.2004.09.018
1440