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Seminars in Surgical Oncology 6:231-233 (1990)

Incidence of Regional Lymph Node Metastasis in


Operable Osteogenic Sarcoma
EDUARDO CACERES, MD, MAYER ZAHARIA, MD, FRCR, AND RUTH CALDERON, MD
From the Instituto Nacional de Enfermedades NeoplAsicas, Lima, Peru
Records of 182 consecutive patients with the diagnosis of operable osteo-
genic sarcoma, treated between 1954 through 1980 by the Breast, Bone
and Mixed Tumors Department of the Instituto Nacional de Enfermedades
Neoplasicas (Lima, Peru), were reviewed to study the incidence of re-
gional lymph node metastases in this disease.
All the patients included in this study had radical surgery, which means
the complete resection of the bone where the tumor is located, including
the proximal joint, which permitted excision of the regional lymph nodes.
Nineteen patients (10.4%) had evidence of sarcoma metastatic to drain-
ing lymph nodes. A comprehensive analysis of the literature shows that
the incidence of metastasis to the lymph nodes in this study, is higher than
those cited in a review of the literature, probably due to the policy in the
management of osteogenic sarcoma in our institution, during the period of
study.
KEY WORDS: major amputations, eradication of lymph nodes, literature review
INTRODUCTION
At the Instituto Nacional de Enfermedades Neoplasi-
cas (INEN), since 1954, osteogenic sarcoma has been
treated by complete resection of the bone at the location
of the tumor, including the proximal joint, which permits
excision of the regional lymph node.
Twenty years ago, a clinicopathologic analysis on the
incidence of lymph node metastasis occurring in 35 con-
secutive cases of osteogenic sarcoma treated by radical
surgery, was made by Caceres et al. [l]. This is an
extension of that study and comprises 182 patients, in-
cluding the 35 previous reported cases are included.
Traditionally, it has been stressed that sarcomas
spread by the vascular system and seldom by the lym-
phatic system. However, with bone and soft tissue sar-
coma treated by radiation therapy and chemotherapy,
lymphatic metastasis occurs if the patient survives long
enough 121.
Tumor cells may penetrate the bloodstream either in
the primary tumor, by lymphatic or venous connections
in a lymph node, or by passage up to the lymphatic chain
to the thoracic duct. Whether lymph nodes can serve as
a temporary filter for metastatic tumor cells still is not
clear [3]. In most of the experimental animal systems
used to investigate this, normal nodes have been sub-
0 1990 Wiley-Liss, Inc.
jected to an influx of a large number of tumor cells, a
situation that may not be analogous at all to the regional
lymph nodes in the early stage of tumor spread in hu-
mans [4]. The development of metastasis is a highly
selective, complex process that is dependent on the in-
terplay of host and tumor cell properties.
MATERIAL AND METHODS
We reviewed the charts of 182 patients with osteo-
genic sarcoma of the extremities treated by radical sur-
gery by the Breast, Bone and Mixed Tumors Department
of the Instituto Nacional de Enfermedades Neoplasicas
(INEN) (Lima, Peru) between January 1963 and Decem-
ber 1980. Patients considered operable at the time of
diagnosis and those who underwent major amputations
(modified hemipelvectomy , interscapulothoracic ampu-
tation, forequarter-mid-thigh amputation) including re-
gional lymph node in the surgical specimen, form the
basis of this study. Patients with parosteal sarcoma were
excluded from the study.
Patients with local regional relapses or distant metasta-
sis were excluded. The lack of metastasis was routinely
Address reprint requests to Dr. Eduardo Caceres, Instituto Nacional de
Enfermedades Neoplasicas, Lima 34, Peru.
232 Caceres et al.
assessed by complete physical examination, chest radi-
ography, lung linear tomography of the chest, bone scan,
and blood chemistries performed at the time of presen-
tation at INEN.
There were 182 patients that conformed to the require-
ments of the study, consisting of 105 men and 77
women, ranging in age from 2 to 38 years. The primary
tumor location was femur 148 (81.3%), humerus 8
(4.4%), tibia 23 (12.7%), fibula 2 (l.l%), and scapula 1
(0.5%). Most patients had large tumors, with the small-
est 10.5 cmin diameter and the largest 16 cm.
Surgical treatment was as follows: 148 underwent
modified hemipelvectomy , 9 interscapulothoracic ampu-
tation, and 25 mid-thigh amputation. From the operative
specimen, a11the lymph nodes from the femoral iliac,
axillary , and popliteal regions were individually dis-
sected and examined histologically for metastasis. In
each case, the microscopic picture was carefully com-
pared with the primary tumor; only those that were com-
patible were accepted as metastasis. The characteristics
of the 182 patients included in the study are presented in
Table I.
INCIDENCE OF LYMPH NODE METASTASIS
Metastatic spread of osteogenic sarcoma of bone from
the original bone site to the regional lymph nodes is not
a frequent event in the natural history of this disease; it is
a subject that has received little attention in the literature.
It is difficult to estimate the true incidence of lymph
node metastasis in osteogenic sarcoma. Data are scant,
and most published series provide relatively brief com-
TABLE I. Clinical Characteristics of 182 Patients Treated for
Osteogenic Sarcoma by Radical Surgery, in Which Lymph Node
Metastasis Was Investigated
ments and imprecise information regarding lymph node
metastasis. In a review of the literature, five studies
[ 1,5431 were devoted to lymph nodes spread from osteo-
genic sarcoma.
Detection of metastasis to regional lymph nodes at
diagnosis of the primary lesion is even less frequent.
Occasionally, however, it is possible to visualize in the
radiographic picture an ossifying metastasis in the re-
gional lymph node [9], since bone formation in the pri-
mary lesion and the metastasis is a peculiar characteristic
of these tumors (Fig. 1).
Regional lymph node involvement occurred in 10.4%
of the 182 patients treated by radical surgery at INEN
from 1963 through 1980. This observation is in disagree-
ment with those from other centers (Table 11), which
report a lower incidence.
This finding may have been influenced by the overall
design of our therapeutic procedure, which includes the
eradication of the regional lymph nodes; the probability of
metastasis depends on histologic grade of the tumor and
size of the primary sarcoma. All our tumors were larger
than the average reported in the literature (10.5-16 cm).
No. of patients 8
Sex
Female 77 42.3
Male 105 57.7
18 9.9
135 74.1
24 13.2
5 2.8
Site of primary tumor
Femur 148 81.3
Humerus 8 4.4
Tibia 23 12.7
Fibula 2 1.1
Scapula 1 0.5
Treatment of the primary tumor
Fig. 1. Osteogenic sarcoma of the humerus, with an ossifying lymph
node metastasis. Patient alive 24 years after interscapulothoracic am-
putation. (Reproduced with the permission of J .B. Lippincott Co.,
Hemipelvectomy 148
Mid-thigh amputation
Interscapulothoracic amputation 9
25 13.8 from Cancer, Vol. 30, pp. 63-38, 1972.)
Node Metastasis and Operable Osteogenic Sarcoma
233
TABLE 11. Incidence of Involvement of Lymph Nodes in Series
of Patients Treated for Osteogenic Sarcoma
Cases with
involved nodes
No. of
Investigators cases N % Comments
Jenkin et al. [5] 51 2 3.9
Caceres et al. [l] 35 4 11.4
Rao and Nagaraj [6] 139 2 1.4
McKenna et al. [7] 276 18 6.5
Weingrad and
Rosenberg [8] 31 1 3.2
Jeffree et al. [l l ] 1 24 4 3.2
Caceres et al. 182 19 10.4
Phelan et al. [lo] 12 6 50.0 Autopsy
McKenna et al. [7] 48 15 31.3 Autopsy
Jeffree et al. [l 11 29 3 10.0 Autopsy; regional
hmDh nodes
This series included 35 cases previously reported.
There are few reports in the literature on the incidence
of lymph node metastasis in autopsy material. Phelan
and Cabrera [lo] reported an incidence of 50% in 12
patients for whom a complete autopsy report was avail-
able and in the series of McKenna et al. [7], 15 of 48
patients (3 1.3%) had involvement of nodes at the time of
autopsy, suggesting a progressive increase in metastasis
during the course of the disease.
Jeffree et al. [ 111 found 10% of regional lymph node
metastasis of the 29 autopsied cases of tumors of the long
bones and in only 3% of the 124 clinical records. How-
ever, none of these figures approaches the 50% fre-
quency of lymph node involvement reported by Makai et
a1. [ 121 on lymphographic evidence.
DISCUSSION
There has been no internationally accepted method of
staging osteogenic sarcoma that could help us in deter-
mining the spread of disease. Traditionally, it has been
stated that lymph node metastases are seldom observed
or occur only occasionally in patients with osteogenic
sarcoma. This has been shown to be a misconception, as
many of these tumors metastasize directly to the regional
lymph node in the operable stage of the disease, and the
eradication of these lymph nodes represents an integral
part of the treatment policy.
The prognostic significance of the regional lymph
node in osteogenic sarcoma and their role in the immune
response against osteosarcoma has been suggested by
Shrikhande and Rao [13], who have stressed its impor-
tance and suggest that preservation of regional nodes in
cases of osteogenic sarcoma is justified.
The involvement of regional lymph nodes has been
accepted as a powerful predictor of a poor outcome for
patients with osteogenic sarcoma. In our experience, the
results are more encouraging; 4 of 19 patients (21%)
remain free of disease for more than 5 years and 1 female
patient with osteogenic sarcoma of the humerus is alive
without evidence of disease for more than 24 years (see
Fig. 1). It is stressed that a significant number of osteo-
genic sarcomas metastasize to the lymph nodes, and the
eradication of these lymph nodes represents an integral
part of treatment policy.
REFERENCES
1. Caceres E, Zaharia M, Tantalean E: Lymph node metastasis in
osteogenic sarcoma. Surgery 65:421-422, 1969.
2. Lee YTNM: Lymph node involvement in soft tissue and bone
sarcomas. In Weiss L, Gilbert MA, Ballon SC (eds): Lymphatic
System Metastasis. Boston: GM Hall, 1980, 410433.
3. Sugarbaker EV: Cancer Metastasis: A Product of Tumour-Host
Interactions. Vol. 3. Chicago: Year Book Medical Publishers,
4. CamI: Lymphatic Metastasis. Cancer Metastasis Rev 2:307-319,
1983.
5. Jenkin RDT, Allt WEC, Fitzpatrick PJ: Osteosarcoma. An as-
sessment of management with particular reference to primary ir-
radiation and selective delayed amputation. Cancer 30:393-400,
1972.
6. Rao RS, Nagaraj D: Prognostic significance of the regional lymph
nodes in osteosarcoma. J Surg Oncol9:123-130, 1977.
7. McKenna RJ, Schwinn CP, Soong KY, Hinginbotham NL: Sar-
comata of the osteogenic series (osteosarcoma, fibrosarcoma,
chondrosarcoma, parosteal osteogenic sarcoma and sarcoma aris-
ing in abnormal bone). An analysis of 552 cases. J Bone Joint
Surg 48A:1-26, 1966.
8. Weingrad DN, Rosenberg SA: Early lymphatic spread of osteo-
genic and soft tissue sarcomas. Surgery 84:231-240, 1978.
9. Case Records of the Massachusetts General Hospital: Osteogenic
sarcoma of humerus, with ossifying metastasis in the regional
nodes. N Engl J Med 225:953-956, 1941.
10. Phelan J T, Cabrera A: Osteosarcoma of bone. Surg Gynecol Ob-
stet 118:33&336, 1964.
11. Jeffree GM, Price HG, Sisson HA: The metastatic patterns of
osteosarcoma. Br J Cancer 32537-107, 1975.
12. Makai F, Belan A, Malek P: Lymphatic metastasis of bone tu-
mours. Lymphology 3:109-113, 1971.
13. Shrikhande SS, Rao RS: Histopathological study of regional
lymph nodes in osteosarcoma. J Surg Oncol 9:371-377, 1977.
1979, 1-59.

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