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. 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