Hindawi Publishing Corporation
Volume 2011, Article ID 457532, 4 pages
EwingSarcoma: AnEponymWindowto History
Timothy P. Cripe1,2
1Division of Hematology/Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, ML7015, OH 45229, USA
2University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Correspondence should be addressed to Timothy P. Cripe, firstname.lastname@example.org
Received 27 June 2010; Accepted 30 October 2010
Academic Editor: R. Pollock
Copyright © 2011 Timothy P. Cripe. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
and influential. He essentially launched oncology as a discipline with the publication of his seminal textbook and founded the
Since his initial report, these organizations have helped us achieve numerous milestones in understanding and treating patients
with Ewing sarcoma.
There are thousands of medical eponyms, and keeping
track of even a small number is a constant challenge for
medical students. At first, such esoteric labels for disease
processes or syndromes seem arcane, especially when the
underlying molecular defects or mechanisms are known,
making much more precise descriptors readily available.
But attaching a person’s name to a disease or therapy
provides a point-of-entry for historical discovery, which may
lead to important insights and perspectives that would not
otherwise be apparent. The risk of using an eponym, of
course, is a reductionist tunnel-vision; one tends to think the
person made a singular contribution to medicine. In reality,
most historical figures had a far greater impact on their field
than a simple eponym would imply. Such is certainly the
case with James R. Ewing, who was a pioneer in the field
of cancer research, and whose vision continues to steer our
cancer research enterprise nearly a century later.
2.James Ewing:FromModest Beginnings to
James Ewing’s biography has been recounted in several
publications [1–3], but some of the highlights are worth
retelling. He was one of five children of a judge, born
in Pittsburgh on Christmas Day in 1866. At age 14, he
suffered from osteomyelitis of his femur after he was injured
while ice skating  and was bedridden for months. He
occupied much of this time being tutored and entering
contests, and in a turn of events that may have influenced
his career choice, he won a microscope in one contest for
his word play on “Constantinople.” Shortly after completing
his medical training, he married Catherine Halsted at the
turn of the century, and within two years became a father.
Unfortunately, his wife and unborn second son died during
childbirth in 1903, and he remained a widower the rest
of his life. His resulting personal reclusivity may have
contributed to his professional productivity, as his seminal
cancer textbook took 10 years to write “including holidays,
nights and weekends” .
By all accounts, James Ewing was an academic giant. He
assembled an impressive curriculum vitae, first studying as
an undergraduate at Amherst College and then completing
his medical training at the prestigious New York College
of Physicians and Surgeons in 1891. After a brief stint at
the Western Pennsylvania hospital, he did his internship
at the Roosevelt Hospital and Sloane Maternity, where he
cultivated his interest in anatomic pathology. He volunteered
for a year as a contract surgeon to the US army, then
in 1899 he managed to land the very first professorship
of pathology at the recently minted Medical College of
Cornell University in New York City. He published his first
textbook only two years later, Clinical Pathology of Blood:
A Treatise on the General Principles and Special Applications
of Hematology. He remained in his position at Cornell for 33
As a young professor, Ewing began to study cancer in
animals, such as canine lymphosarcoma, and he quickly
became a noted spokesman for cancer research and an
avid fundraiser. He established the P. Huntington Fund
for Cancer Research in 1902, cofounded the American
Association for Cancer Research in 1907, and founded
the American Society for the Control of Cancer, now
the American Cancer Society, in 1913. In addition, he
founded the Journal for Cancer Research and teamed with
philanthropist James Douglas to create Memorial Hospital
of New York, where he later became its first director
of research. In his leadership position, Ewing guided the
institution’s evolution into the nation’s first cancer center,
now known as Memorial Sloan-Kettering Cancer Cen-
Ewing’s most influential academic contribution was his
1919 cancer textbook, Neoplastic Disease: A Textbook on
Tumors, of which he was the sole author. This comprehensive
treatise on cancer spanned early cancer history to modern
biologic theory to detailed pathologic descriptions and clas-
sifications of all known cancer types. With this publication,
Ewing essentially founded oncology as a medical subspe-
cialty. In 1931, Ewing’s broad contribution to the cancer field
was recognized by Time magazine, which featured a sketch
of his visage on the cover, calling him “Cancer Man Ewing”
Despite his intensive work schedule, a limp from hip
ankylosis, and a nagging facial neuralgia, Ewing managed to
maintain his interest in sports, playing tennis on weekends
and taking in professional baseball games. Although his
adulthood was spent in New York, he remained an ardent
fan of the Pittsburgh Pirates and is said to have once skipped
one of his own lectures when they were in town to play
the New York Giants (then a baseball team). According
to accounts, three of his students were also truant and
spotted him at the game . Skipping his classes was
probably a rare event, as he was said to be “beloved by
students and colleagues; a physician of the highest ideals”
Ironically, the Cancer Man died of bladder cancer in
1943 at the age of 76, and at autopsy was also found
to have low-grade prostate cancer . His life’s impact
was evident at his funeral, which was attended by over
a thousand people. Ewing shed a bright light on cancer,
bringing it into the public eye long before it became
a national priority. His vision of establishing six $10
million cancer centers throughout the United States was
a blueprint for the current network of National Cancer
Institute designated cancer centers, which now number 65
and approach $300 million in core funding. As an Amherst
alumnus, James Ewing certainly fulfilled the College’s motto,
Terras Irradient, meaning “Let them give light to the
3.Diffuse Endothelioma Tumor
In 1921, two years after he published the first edition of his
cancer textbook, Dr. Ewing reported in the Proceedings of
the New York Pathological Society several cases of a new
bone cancer he called “diffuse endothelioma of bone,” which
ultimately became his eponym . In his paper, he described
a 14-year-old girl who developed a tumor of the radius that
was thought to be an osteosarcoma, which was already well
known to clinicians and was usually treated by amputation.
Although radiotherapy was increasingly being used for
other cancers, osteosarcoma was known to be radioresistant.
For reasons not known, this particular patient was given
therapies other than amputation, including eight injections
of Coley’s toxin. That treatment was derived from bacterial
erysipelas cultures and used by William Coley via direct
intratumoral injection to induce an inflammatory response
to the toxin and the tumor . After these injections failed
to improve the tumor, she was treated at Memorial Hospital
with 12,760 miCu-hr of radium every two weeks for three
doses, and surprisingly experienced a complete response
by examination and plain films. The effect of radiotherapy
suggested at least to some clinicians that the tumor was
distinct from osteosarcoma. After the tumor unfortunately
recurred, the “conflict of opinion” prompted a biopsy to
settle the issue. The pathology was indeed different from
osteosarcoma, and Ewing used the vague term “round cell
sarcoma.” He thought the cells looked like blood vessels of
the bone, and thus termed it “endothelioma of bone.”
In his report, Ewing recounted six other similar cases he
had seen in the prior four months. The patients were 14–19
years old, and the primary tumor sites were the tibia, ulna,
ischium, skull, and scapula. He described the tumors as slow
distinguished his series from osteosarcoma: “A large portion
or the whole of the shaft is involved, but the ends are gener-
shaft is slightly widened, but the main alteration is a gradual
diffuse fading of the bone structure. Bone production has
been entirely absent... The radiograph is therefore rather
specific.” Based on Ewing’s publication, a few years later the
noted Boston surgeon, Ernest Codman, referred to this new
entity as Ewing sarcoma.
Interestingly, many of the features noted by Ewing in
his original report of only a few cases nearly 90 years ago
have withstood the test of time. Ewing sarcoma occurs most
commonly in adolescents, may appear in flat as well as long
bones, most often in the diaphysis rather than the epiphysis,
and radiation is a primary treatment modality. Of note, in
an ironic crisscrossing of eponyms, Ewing sarcoma is one
of the main differential diagnoses of Codman’s triangle, the
periosteal elevation visible on plain films that often results
from a bone tumor.
In the first 40 years after Ewing’s initial description, advances
in our understanding of Ewing sarcoma were limited to
descriptive isolated case and series reports, which better
1920’s1930’s 1940’s 1950’s1960’s 1970’s 1980’s 1990’s 2000’s
Named after Ewing
Case report descriptions
5 drugs > 3
James Ewing died
Figure 1: Timeline of historical milestones for Ewing sarcoma. See text for details. Survival data for children diagnosed at age <15 years old
are from Rosen et al.  and from the Surveillance, Epidemiology and End Results 9 registries as summarized in the work of Smith et al. .
defined the clinical spectrum of Ewing sarcoma (Figure 1).
Surgery and radiation were the only means of therapy
until the 1960s, when Ewing sarcoma was among the
first solid tumors found to be responsive to chemotherapy
including vincristine, daunomycin, and actinomycin D [8–
11]. Identification of the activity of ifosfamide and etoposide
as single agents each followed over the next two decades
[12, 13], though their combination (IE in Figure 1) took
another decade to be proven useful . Genetic diagnosis
became possible with the identification of a characteristic
chromosomal translocation in the 1980s [15, 16], and the
mechanism of tumorigenesis began to be elucidated with the
cloning of the breakpoint, identifying the EWS-FLI1 fusion
early the next decade . These studies also later enabled
the consolidation of other tumors, such as the clinically
similar but histologically distinct primitive neuroectodermal
tumor, into a common tumor family . Preclinical studies
were better enabled in the 1980s by the development of a
xenograft model . With the increased availability of MRI
in the 1980s  and FDG-PET in the 1990s , new
imaging modalities led the way to improved staging, refined
tumor response data . High-dose chemotherapy with
stem cell rescue was also pioneered for Ewing sarcoma in the
1990s , but after 20 years of use in selected circumstances
its utility is still uncertain . Chemotherapy for Ewing
clinical trials demonstrating that five drugs were better than
three  and that interval compression (every two-week
cycles) was superior to conventional timing (every three-
week cycles) [27, 28].
As a further illustration of Dr. Ewing’s long-lasting
impact, the organizations he founded played roles in each
these milestones, as some of the work was funded by
the American Cancer Society, reported at meetings of the
the Memorial-Sloan Kettering Cancer Center and other such
centers he envisioned. As we enter the last decade leading
toward the century anniversary of his initial case description,
further advances are likely to result from targeted molecular
approaches that are being intensively studied, such as
cell signaling and angiogenic pathways .
While best remembered by his eponym, James Ewing
changed the landscape of cancer care and research by single-
handedly penning the first comprehensive textbook on can-
cer and founding what is now the largest charitable organi-
zation in the world that supports cancer research, the largest
cancer research society in the world, and the largest cancer
center in the United States. His vision of comprehensive
cancer centers throughout the country, which would bring
together diverse experts to study cancer, remains the guiding
principle of our nation’s cancer research infrastructure. Yet
the story of Ewing sarcoma illustrates the slow pace of
medical advancement, at least as it occurred in the 20th
century. At the time of James Ewing’s death, 20 years after
he first identified Ewing sarcoma, little progress had been
and another 20+ years before the EWS-FLI1 translocation
gave insight into its biology, and yet another 20 years before
significant improvements in chemotherapy were realized.
durable, and the survival of patients today has significantly
improved over the past 90 years due to numerous diagnostic,
genetic, surgical, radiotherapeutic, and medical advances
made possible in part through his organizational efforts.
Hopefully such milestones will continue to be realized,
perhaps even at a brisker pace, until the day when all patients
diagnosed with Ewing sarcoma are curable.
The author thanks Lars Wagner for critical review. This
manuscript was supported by the Cancer Free Kids Pedi-
atric Cancer Research Alliance, teeoffagainstcancer.org, and
NCI/NIH Grants R21CA133663 and R01CA114004.
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