History of Bone Tumor Pathology
Moderators: K. Krishnan Unni and Franco Bertoni
Section 1 -
The Registry of Bone Sarcoma: A History
Edward F. McCarthy
There have been many national cooperative efforts led by panels of physicians, usually
pathologists, to formulate nomenclature of particular diseases. Most of these efforts have dealt with
neoplastic diseases, and their goal has been to correlate specific histologic features with a name and a
prognosis. Examples of such panels are The Early Malignant Melanoma Panel, the Wilm's Tumor Study Group,
and the Non-Hodgkin's Lymphoma Pathologic Study Group. These cooperative efforts to formulate
nomenclature have their origin in the vision of one energetic surgeon, Ernest Codman, who, in 1921,
established the Registry of Bone Sarcoma. Working under the auspices of the American College of
Surgeons, Codman's goals were to record living patients with bone sarcoma, to revise inadequate existing
nomenclature, and to learn the behavior of these neoplasms. The project lasted many years and was a
great success. Not only did the Registry accomplish Codman's three goals, it achieved other further
reaching effects. As the first national prospective study, it provided a model for studies of other
diseases. Also, because many hospitals contributed to the Registry, it helped spearhead the movement
toward hospital standardization. Finally, because the Registry depended on the working together of
surgeons, pathologists, and radiologists, cooperative practice became fundamental to the treatment of
Ernest Codman (1869-1940) was a Boston surgeon with a special interest in bones. By 1897,
only a year after Roentgen had discovered x-rays, Codman was emphasizing the importance of this tool in
the clinical management of patients with bone disease . In 1909 he had described the
triangle of reactive periosteal bone adjacent to bone tumors that bears his name . Codman was
also a founding member of the American College of Surgeons, formed in Chicago in 1913 .
In 1920 Codman had a patient with what he thought was a bone sarcoma. The family of this
patient gave Codman a $1,000 gift to find out if any patients survived a bone sarcoma and, if so, what
treatment they had. The treatments available at that time were amputation, x-rays, radium, and Coley's
toxin. Coley's toxin, used from the early 1890s until World War II, was a sterilized suspension of
streptococci cultures which, when inoculated into patients, was believed to enhance their resistance to
Codman began his $1,000 study by writing a letter to every member of the American College
of Surgeons, then about 4,000. The letter began as follows:
Dear Doctor: Have you any living cases of bone sarcoma? I include in this
question, recent cases which are now under treatment and also any cases
which you may consider as having recovered .
The response was a surprise. One hundred and seventy one members responded immediately
and wrote descriptions of patients they believe to have bone sarcoma. In addition, 345 members also
wrote to show their support of the study and suggested that such studies be made of other surgical
Because of this enthusiastic response, Codman was able to persuade the Regents of the
American College of Surgeons to establish the Registry of Bone Sarcoma on June 7, 1921. Fifteen hundred
dollars was appropriated by the College to continue the work . Codman invited two other
experts in bone diseases, James Ewing and Joseph Bloodgood, to work with him. James Ewing (1866-1943)
was a pathologist in New York, at that time working at Cornell University. He had already published his
book, Neoplastic Diseases , and he had just described the entity,
diffuse endothelioma of bone, a malignant tumor which immediately (to his great protests) bore his
name . Joseph Bloodgood (1867-1935), a surgeon and director of surgical pathology at Johns
Hopkins in Baltimore, also had an interest in bone tumors. He had already published his observation
based on his own cases and those he culled from the literature, that "giant cell sarcoma" behaved as a
benign tumor . Thus, the three physicians in charge of the Registry of Bone Sarcoma, were the
country's most respected experts of bone tumors.
Codman continued to solicit cases of bone sarcoma from the members of the College. Only
living patients could be registered. Surgeons sent the clinical history, details of the physical
examination, radiographs, and histologic material (preferably wet tissue) to the Registry's headquarters
of 227 Beacon St. in Boston . The diagnosis and method of treatment was also submitted. The
Registry sought yearly follow-up on each case and thus became the first national prospective study.
Upon receipt, the Registry filed all the submitted material in a numbered envelope. Data
about the case was entered on the face of the envelope. Groups of cases were placed in boxes to be
circulated to other renowned pathologists like Mallory, Wright, or Wolbach, whom the Registry had
enlisted to provide their opinion. Each case was then labeled with the consensus diagnosis.
By 1925, the Registry had collected the clinical history, radiographs, and histologic
material on 560 cases. The results of the analysis of these cases were published that year by Codman in
a small monograph. This monograph represents the first attempt to standardize and disseminate the
nomenclature of a particular disease .
Earlier primitive attempts to classify tumors (including bone tumors) had generally been
based on gross characteristics. However, in 1879, Samuel gross published the first systematic study of
165 cases of bone sarcoma which included histologic analysis . Gross' classification, which
influenced pathologists for many years, was based on two parameters. One was location of the tumor –
whether the tumor was central or periosteal. The other was cell type – giant cell, spindle cell, or
round cell. For example, in his classification there was a central round cell sarcoma and a periosteal
spindle cell sarcoma. Other classification systems were based on the type of neoplastic tissue that
predominated: fibro, myxo, chondro, or osteo. Thus, a sarcoma might be called a fibromyxosarcoma and
other call a chondro-osteosarcoma.
Codman felt that these methods of classifying sarcomas were like classifying dogs
according to the color of their spots. Moreover, observers rarely agreed on the classification of any
sarcoma using these systems. Using the cases submitted to the Registry, Codman proposed a classification
based on combined clinical, radiographic, and histologic features. Cases fell into only eight groups.
The first six represented the primary bone tumors:
- Periosteal fibrosarcoma
- Benign and malignant osteogenic tumors
- Giant cell tumor
- Ewing's tumor
- Myeloma (what today are lymphomas and plasma cell myelomas)
The seventh and eight groups were metastatic carcinoma and non-neoplastic disorders such
as osteiitis fibrosa, myositis ossificans, and bone cysts. Interestingly, this system did not include
chondrosarcoma. It was not until 1930 that Dallas Phemister suggested that this malignant tumor might be
a distinct entity .
Today, we recognize at least twenty specific types of bone tumors. Some of these have
many well-defined subtypes. However, the six categories of bone tumors proposed by the Registry would be
the nucleus of all future classifications.
The Registry made an important observation very early – that many lesions submitted as
bone sarcomas were, in fact, not primary malignant tumors of bone. Of the 560 cases collected by 1925,
about one half were either metastatic carcinomas or non-neoplastic bone diseases. Fortunately, Codman
had urged surgeons to submit cases even if they feared their diagnosis might be proved wrong. By means
of publications and presentations, the Registry sought to raise the awareness that it was easy to
misdiagnose a bone tumor. In 1926, Codman published a paper in which he defined 25 clinical,
radiographic, and histologic features of osteogenic osteosarcoma . It was the first effort by
any physician to rigorously define a disease entity in order to avoid misdiagnosis.
By 1926, the Registry had also confirmed the suspicion that the prognosis for bone sarcoma
was very poor. Of the approximately 250 cases which the members of the Registry agreed were bone
sarcomas, only 17 (4 Ewing's tumors and 13 osteogenic sarcomas) were alive long enough to be considered
cured. All but one of these cases had been treated by amputation. Some had had additional x-ray,
radium, or toxin treatment. The members of the Registry then made a diligent attempt to define the
features of the sarcomas of the 17 surviving patients. Although this attempt was unsuccessful, the
members did conclude that x-ray treatment held great promise.
Codman suspected correctly that the Registry might provide some epidemiologic data.
Because he repeatedly petitioned all the members of the American College of Surgeons, he believed the
Registry was following almost all the cases living at any moment in the United States. He originally
estimated this number to be no more than 500, but as the registry grew he revised this number to 1,000.
He also was convinced that all the surgeons in Massachusetts were contributing all their cases, and
knowing the population of the state, he could calculate the incidence of bone sarcoma to be 1/100,000.
In addition to increasing the knowledge about bone tumors, Codman's project resulted in
several broader benefits for medical practice. The first of these was hospital standardization. That
many hospitals were substandard was evidenced by the frequent diagnostic errors submitted to the Registry
and the often poor quality of the histologic slides, radiographs, and clinical histories. Codman
believed that by participating in the bone sarcoma study, hospitals would be forced to improve – to
produce only good quality radiographs and histologic specimens and to demand accurate and complete
clinical histories. He even subtly hinted that a hospital's unwillingness to send cases to the Registry
indicated inferior practices.
Codman was also interested in patient follow-up, another issue of hospital
standardization. Many hospitals had inadequate follow-up systems. Codman had suggested mechanisms of
patient follow-up to the American College of Surgeons as early as 1913 . He believed in the
importance of the concept of "end results" – that every hospital should follow a patient long enough to
determine the final results of treatment. The "end result" concept was the foundation of the Registry of
Bone Sarcoma. Codman believed that hospitals which submitted cases would have to be meticulous about
In addition to hospital standardization, another lasting effect of the Registry was the
model it provided for national clinical research. The Registry's success proved that, guided by a panel
of experts, physicians across the nation could communicate and use their collective experience to benefit
future patients. Patients with rare diseases could not longer be treated at the caprice of an individual
surgeon who had never seen such a case before. Rather, each case would be backed by the collective
experience of the entire medical world. Codman, Ewing, and Bloodgood also envisioned that the cases
collected would be a library of information to be built on by future researchers.
The final effect of the Registry of Bone Sarcoma was to establish the principle
fundamental to modern orthopedic practice – that bone diseases are not isolated radiologic or histologic
entities. Instead, they are defined by a combination of clinical, radiographic, and histologic
features. This was the principle of the Registry's classification system, and it demands close
cooperation of surgeons, radiologists, and pathologists.
The Registry of Bone Sarcoma continued for many more years after the publication of its
first classification system. By 1925, it had outgrown its facilities in Boston and was transferred to
Chicago where, fully funded by the American College of Surgeons, Dallas Phemister was appointed to be its
supervisor. In 1927, 700 cases were on file and were summarized by Anatole Kolodny of the University of
Iowa . The number of cases was so large by 1939 that Ewing requested that only unusual cases
be submitted. The collection was dormant during World War II, and in 1953 the entire collection, finally
closed, was presented to the Armed Forces Institute of Pathology in Washington .
The patient whose family gave Ernest Codman $1,000 to start his project eventually died
and was found to have metastatic carcinoma, not a bone sarcoma. But the gift has benefited bone tumor
patients ever since.
- Bloodgood, J.C. The Conservative Treatment of Giant-Cell Sarcoma, with the Study of Bone Transplantation. Ann. Surg., 56:210-39, 1912.
- Codman, E.A. The use of the X-Ray and Radium in Surgery. In W.W. Keen, Surgery, Its Principles and Practice by Various Authors. W.B. Saunders, Philadelphia. 5:1170, 1909.
- Codman, E.A. The Registry of Cases of Bone Sarcoma. Surg. Gynecol. Obstet., 34:335-343, 1922.
- Codman, E.A. The Method of Procedure of the Registry of Bone Sarcoma. Surg. Gynecol. Obstet., 38:712-721, 1924.
- Codman, E.A. Bone Sarcoma: An Interpretation of the Nomenclature Used by the Committee on the Registry of Bone Sarcoma of the American College of Surgeons. Paul B. Hoeber, Inc., New York. 1925.
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- Ewing, J. Diffuse Endothelioma of Bone. Proc. NY Path. Soc. 21:17-24, 1921.
- Gross, S.W. Sarcoma of the Long Bones; Based on a Study of One Hundred and Sixty-Five Cases. Am. J. Med. Sci. 78:2-57, 338-77, 1879.
- Kolodny, A. Bone Sarcoma: The Primary Malignant Tumors of Bone and the Giant Cell Tumor. Surgical Publishing Co., Chicago. 1927.
- Obituary. Ernest Amory Codman. Trans. Am. Surg. Assoc. 59:611-613, 1941.
- Peltier, L.F. Orthopedics, A History and Iconography. Norman Publishing, San Francisco, 1993.
- Phemister, D. Chondrosarcoma of Bone. Surg Gynecol. Obstet. 50:216, 1930.
- Stephenson, G.W. American College of Surgeons at 75. American College of Surgeons, Chicago. 1990.