Table Of Content54
Recent Results
in Cancer Research
Fortschritte der Krebsforschung
Progres dans Ies recherches sur Ie cancer
Edited by
V. G. Allfrey, New York· M. Allgower, Basel
K. H. Bauer, Heidelberg· I. Berenblum, Rehovoth
F. Bergel, Jersey· J. Bernard, Paris· W. Bernhard,
Villejuif· N. N. Blokhin, Moskva· H. E. Bock,
Tubingen . W. Braun, New Brunswick· P. Bucalossi,
Milano· A. V. Chaklin, Moskva· M. Chorazy,
Gliwice . G. J. Cunningham, Richmond
G. Della Porta, Milano· P. Denoix, Villejuif
R. Dulbecco, La Jolla· H. Eagle, New York· R. Eker,
Oslo· R. A. Good, New York· P. Grabar, Paris
H. Hamperl, Bonn· R. J. c. Harris, Salisbury
E. Hecker, Heidelberg· R. Herbeuval, Nancy
J. Higginson, Lyon· W. C. Hueper, Fort Myers
H. Isliker, Lausanne· J. Kieler, K@benhavn
G. Klein, Stockholm· H. Koprowski, Philadelphia
L. G.Koss, New York . G.Martz,Zurich
G. Mathe, Villejuif . o. Muhlbock, Amsterdam
W. Nakahara, Tokyo· L. J. Old, New York
V. R. Potter, Madison· A. B. Sabin, Rehovoth
L. Sachs, Rehovoth . E. A. Saxen, Helsinki
C. G. Schmidt, Essen· S. Spiegelman, New York
W. Szybalski, Madison· H. Tagnon, Bruxelles
R. M. Taylor, Toronto· A. Tissieres, Geneve
E. Uehlinger, Zurich· R. W. Wissler, Chicago
Editor in Chief: P. Rentchnick, Geneve
Malignant
Bone Tumors
Edited by
E. Grundmann
With 116 Figures
Springer-Verlag
Berlin. Heidelberg. New York 1976
VIth International Symposium of the "Gesellschaft zur
Bekampfung der Krebskrankheiten Nordrhein-Westfalen e. V."
Di.isseldorf October 17/18 1974
Prof. Dr. EKKEHARD GRUNDMANN, Pathologisches Institllt,
4400 Mi.inster, Westring 17
Sponsored by the Swiss League against Cancer
ISBN·13: 978·3·642·80999·6 e-ISBN-13: 978-3-642-80997-2
001: 10.1007/978-3-642-80997-2
Library of Congress Cataloging in Publication Data. Gesellschaft zur Bekampfung
der Krebskrankheiten Nordrhein-Westfalen. Malignant bone tumors. (Recent results
in cancer research; 54.) Proceedings of the 6th international symposium of the
Gesellschaft zur Bekiimpfung der Krebskrankheiten Nordrhein-Westfalen held in
Dusseldorf, Oct. 17-18, 1974 and sponsored by the Swiss League Against Cancer.
Bibliography: p. Includes index. 1. Bones - Cancer - Congresses. I. Grundmann,
Ekkehard. II. Schweizerische Nationalliga fur Krebsbekampfung und Krebsfor
schung. III. Series. [DNLM: 1. Bone neoplasms - Congresses. WI REI06P v.
54/WE258 M251 1974] RC261.R35 vol. 54 [RC280.B6] 616.9'94'008s [616.9'9471]
75-33987.
This work is subject to copyright. All rights are reserved, whether the whole or
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© by Springer-Verlag Berlin' Heidelberg 1976.
Softcover reprint of the hardcover I st edition 1976
The use of registered names, trademarks, etc. in this publication does not imply,
even in the absence of a specific statement, that such names are exempt from
the relevant protective laws and regulations and therefore free for general use.
Contents
Introduction
Bone Tumors - A Challenge for Cooperation.
E. GRUNDMANN 1
I. Experimental Tumors
Comparative Pathology of Bone Tumors in Animals, with
Particular Emphasis on the Dog. S. W. NIELSEN 3
Bone Tumors Induced by Inhalation of 238PU0 in Dogs.
2
J. F. PARK, J. E. LUND, H. A. RAGAN, P. L. HACKETT, and
M. E. FRAZIER 17
Experimental Induction of Bone Tumors by Short-Lived
Bone-Seeking Radionuclides. W. GassNER, O. HUG, A. Luz,
and W. A. MULLER 36
II. Pathogenesis
Etiology of Childhood Bone Cancer: Epidemiologic
Observations. R. W. MILLER 50
The Endogenous Origin and Transmission of RNA Viral
Genomes that Code for Cancer. R. J. HUEBNER 63
Pathogenesis of Radiation and Virus-Induced Bone Tumors.
M. P. FINKEL, C. A. REILLY JR., and B. O. BISKIS 92
Ill. Pathology
The WHO Classification of Bone Tumors. H. A. SISSONS 104
Primary Malignancy, Secondary Malignancy and Semi
malignancy of Bone Tumors. E. UEHLINGER 109
V
Common Errors Made by Pathologists in the Diagnosis of Bone
Tumors. L. V. ACKERMAN 120
Aspiration (Puncture or Needle) Biopsy in Bone Lesions.
F. SCHAJOWICZ and J. HOKAMA 139
Cytologic and Cytochemical Behavior of Primary Malignant
Bone Tumors. M. SALZER-KuNTSCHIK 145
Histochemical and Electron-Microscopic Aspects of Bone
Tumor Diagnosis. W. REMAGEN, F. GUDAT, and P. HEITZ 157
IV. Immunology
Morphological, Biological, Immunological and Biochemical
Studies on Bone Tumors of Animals and Man.
L. DMOCHOWSKI 166
Immunologic Aspects of Human Sarcomas. D. J. PRITCHARD,
J. C. IVINS, and R. E. RITTS, JR. 185
The Immune-Status in Patients with Bone and Soft-Tissue
Sarcomas. R. KOTZ, W. RELLA, and M. SALZER 197
Laboratory Models of Minimal Residual Cancer: Develop
ment and Preliminary Immunotherapy Studies.
CH. M. SOUTHAM 206
V. Therapy
The Treatment of Malignant Bone Tumors by Conservative
Surgery. R. C. MARCOVE 218
Management of Osteogenic Sarcoma at the Mayo Clinic.
J. C. IVINS and D. J. PRITCHARD 221
Surgical Treatment of Solitary Bone Cysts. H. H. MATTHIASS
and M. IMMENKAMP 231
Resection of Malignant Bone Tumors. M. SALZER and
K. KNAHR 239
Giant-Cell Tumors and Chondrosarcomas: Grading, Treatment
and Results (Studies of 209 and 131 Cases).
M. CAMPANACCI 257
X-Ray Therapy of Primary Bone Tumors. W. HOEFFKEN 262
Subject Index 271
VI
List of Participants
L. V. ACKERMAN, Health Sciences Center, Dept. of
Pathology, State University of New York, Stone Brook,
N. Y. 11790.
M. CAMPANACCI, Istituto Ortopedico Rizzoli, Clinica
ortopedica dell'Universid., 1-40100 Bologna.
L. DMOCHOWSKI, Univ. of Texas, Dept. of Virology,
M. D. Anderson Hospital, Houston/Texas 77025.
W. GassNER, Pathologisches Institut, Klinikum rechts d. Isar
cler TU, Ismaninger StraBe 22, D-8000 Munchen 80.
E. GRUNDMANN, Pathologisches Institut der Universidit,
Westring 17, D-4400 Munster.
W. HOEFFKEN, Strahleninstitut der Allgem. Ortskrankenkasse
Koln, MachabaerstraBe 19/27, D-5000 Koln 1
R. J. HUEBNER, National Inst. of Health, National Cancer
Institute, Viral Carcinogenesis Branch, Bethesda/Md. 20014.
M. IMMENKAMP, Orthopadische Universitatsklinik Munster
HufferstraBe 27, D-4400 Munster.
J. C. IVINS, Mayo Clinic, Dept. Orthopedic Surgery,
Orthopedic Oncology, Rochester/Minn. 55901.
R. KOTZ, Orthopadische Universitatsklinik, Garnisongasse 13,
A-l090 Wien.
R. C. MARCOVE, 517, East 71st Street, New York/
N. Y. 10021.
H. H. MATTHIASS, Orthopadische Universitatsklinik
Munster, HufferstraBe 27, D-4400 Munster.
W. MILLER, National Inst. of Health, National Cancer
Institute, Epidemiology Branch, A 521 Landow Building,
Bethesda/Md. 20014.
S. W. NIELSEN, Cornell University, Dept. of Pathology,
Ithaca/N. Y. 14850.
J. F. PARK, Battelle Pacific NW. Lab., Battelle Boulevard,
Richland/Wa. 99352.
VII
H. POPPE, Radiologische Klinik der Universitat,
Gomerstra~e 10, D-3400 Gottingen.
D. J. PRITCHARD, Mayo Clinic, Dept. Orthopedic Surgery,
Orthopedic Oncology, Rochester/Minn. 5590l.
CH. A. REILLY, JR., Argonne National Laboratory,
Experim. Radiation Pathology, Building 340, 9700 South
Cass Avenue, Argonne/Ill. 60439.
W. REMAGEN, Pathologisches Institut der Universitat,
Schonbeinstra~e 40, CH-4056 Basel.
M. SALZER, Orthopadische Univ.-Klinik, Garnisongasse 13,
A-1090 Wien.
M. SALZER-KuNTSCHIK, (Frau), Pathol.-Anatomisches Institut
der Universitat, Spitalgasse 4, A-1090 Wien.
F. SCHAJOWICZ, WHO/Osteo-articular Pathology Center,
Hospital Italiano, Gascon 450, Buenos Aires.
H. A. SISSONS, University of London, Institute of Ortho
paedics, Dept. of Morbid Anatomy, 234, Great Portland
Street, London W1N 6AD.
CH. M. SOUTHAM, Jefferson Medical Center, Dept. of
Medicine, Div. Medical Oncology, Philadelphia/Pa. 19107.
E. UEHLINGER, Pathologisches Institut der Universitat,
Kantonsspital, Schmelzbergstra~e 12, CH-8006 Zurich.
VIII
Introduction
Bone Tumors - A Challenge for Cooperation
E. GRUNDMANN
Among the wide variety of human tumors, those of the skeletal system
have an exceptional position in several respects. Above all, they are
comparatively rare, and that is why reliable diagnostic criteria were
compiled only recently, that is during the last three decades. It is
only five years since the outlines of an international code of classi
fication were traced. The code was applied and discussed critically
and with varying results by several international working groups. Cer
tain drawbacks are due to the broad and manifold spectrum of histolo
gic manifestations in neoplastic bone. Even the best experts in dia
gnostic histology would hardly be able to classify more than 85% of all
bone tumors after the proposed code system. For quite a long time the
osteoclastic giant cells, observed in almost any kind of bone tumor,
have so much fascinated the histologist's eye that he was apt to pro
claim the diagnosis "brown giant cell tumor" for almost any osteoclas
tic tumor regardless of its benignity or malignancy. Nowadays the group
of "giant cell tumors" though'restricted, still remains disputed in
terms of malignancy and benignity. The problem will certainly not be
settled in a definite way without extensive follow-up studies. In this
context we may see actual progress in new regional. bone tumor registries
being set up after the American example in many countries, among them
the German Federal Republic. The collection and registration of cases
will not only facilitate epidemiologic perspectives, but also the con
vention on a world-wide classification code for frequent tumor types,
accompanied by a separate list of rare and exceptional cases. The in
ternational exchange of data is called for, and the start has been most
auspicious.
The diagnosis of a bone tumor has to be based not only on histology,
but also on the roentgenogram. If the pathologist is not well trained
in the interpretation of roentgenograms - and this may be normal -
close cooperation between X-ray specialist and pathologist are a pre
requisite of effective and detailed diagnosis. In many cases cytologic
methods will facilitate, accelerate, or verify the results of diagnosis.
The additional support of electron microscopy is, for the present,
restricted to some very special cases.
An exact and detailed diagnosis is the prerequisite of adequate therapy.
Although surgery will always be predominant in therapy, the extent and
method of a surgical intervention will depend on the respective diagno
sis. As in diagnostics, experience has to set the scale in therapy plan
ning. Surgery must be as sparing as possible and as radical as neces
sary. In many cases it can be successfully supplemented by radiothera
py and even by chemotherapy in some cases, or by recently developed
methods of immunotherapy.
Whereas malignant tumors of epithelial origin tend to occur in persons
of advanced age, the most frequent of the primary malignant bone tumors
will appear before the age of 40. This was observed especially in osteo
sarcoma and in Ewing's sarcoma. There is a rule in malignant tumors of
the bone: when the P3tient is you~ger than 40, you have to look out
first for a primary bone tumor, if he is over 40, you have to think of
metastases. This preferential manifestation in younger people increases
the responsibility with regard to diagnostic and therapeutic measures.
Based upon experiments, the virus hypothesis of tumorigenesis is be
coming much more probable with respect to malignant bone tumors. Corres
pondingly bone tumors may be seen in analogy to hemoblastoses, the
origin of which is also found in the skeletal system. The fact that
ionizing radiation is a potential cause of bone tumors, has its bearings
on another inter sting problem: it appears possible that ionizing radia
tion is able to activate latent tumor viruses. A similar concept is,
by the way, discussed for malignant epithelial tumors, and this is how
results and conclusions drawn from bone tumor findings, may become para
digmatic for cancer research as a whole.
We are only at the beginning of our research on etiology and patho
genesis of bone tumors. We are still living in the age of the "hunters
and gatherers." Therefore the exchange of experience among research
groups is of vital importance in the field of bone tumor diagnostics
and therapy. Every bone tumor that is not listed in a registry, will be
lost forever as far as compilation of diagnostic criteria and, in the
end, the improvement of therapy are concerned.
The present volume intends to show some contemporary knowledge about
origin, pathology, and clinical management of bone tumors; its addi
tional purpose will be an appeal for international cooperation in all
these fields.
2
1. Experimental Tumors
Comparative Pathology of Bone Tumors in Animals,
with Particular Emphasis on the Dog
s.
W. NIELSEN
I. OSTEOSARCOMA
The osteosarcoma is the most frequent bone tumor in dogs (Table 1).
It appears characteristically as a localized swelling of long bones
in the metaphysis at the junction of the shaft and epiphysis. The over
lying skin is usually intact, and there is often subcutaneous and intra
muscular edema distal and proximal to the tumor, due to impaired cir
culation. The degree of bone destruction varies a great deal from tu
mor to tumor, ranging from a few osteolytic foci (Fig. 1a) to complete
destruction (Fig. 1b). Advanced muscular atrophy of the affected leg,
resulting from inactivity because of pain or compression of motor ner
ves, is often present in neglected cases. When the tumor is cut, bone is
sometimes felt against the knife. Hemorrhagic areas are scattered among
firmer grayish portions that contain yellowish irregular necroses in
some cases. Sectioning of the regional lymph nodes often reveals these
to be enlarged and mOist, due either to tumor invasion or to congestion.
Table 1. Histologic typing of 133 canine bone tumors (LING et al., 1974)
86 Osteosarcomas
15 Chondrosarcomas
12 Fibrosarcomas
8 Hemangiosarcomas
8 Osteomas
4 Chondromas
A high percentage of metastases are present in the dog, approximately
50 percent of cases necropsied having pulmonary metastases. They ap
pear as multiple, firm, grayish nodules ranging from the size of a pea
to that of a chestnut. When these are cut, osteoid tissue with varying
degrees of calcification can be seen.
Histopathology. It is almost impossible to describe any histologic pic
ture as being characteristic of osteosarcoma. The neoplastic os teo
blasts are either round or spindle-shaped cells. They are situated in
a loose fibrous or myxoid intercellular substance in which foci of tu
mor bone are seen. The amount of bone formation varies widely and does
not seem to be related to the clinical behavior of the tumor. Other
characteristics, which are found to be more closely associated with the
speed of growth, are the cellularity, the number of mitoses, and the
degree of pleomorphism present (Fig. 2). Multinucleated giant cells are
3
