|Year : 2011 | Volume
| Issue : 3 | Page : 335-338
A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs
N Krishnamoorthy, SS Desai, B Rekhi, NA Jambhekar
Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India
|Date of Web Publication||14-Sep-2011|
N A Jambhekar
Department of Pathology, Tata Memorial Hospital, Parel, Mumbai
Source of Support: None, Conflict of Interest: None
Background: Metastasis of soft tissue sarcoma most commonly occurs to the lungs. There are very few studies on histology of pulmonary metastatectomy and hardly any wherein the histology of the primary tumor has been compared with the metastasis. Aims and Objectives: To review histologically all metastatic sarcomas to lung and compare with the primary where available. Materials and Methods: Ninety-five patients with pulmonary metastases from sarcoma were analyzed histologically for type of sarcoma, chemotherapy-related changes, and changes in adjacent lung. Various clinical parameters like laterality, multiplicity, and interval between primary and metastasis were also studied. Results: Osteosarcoma constituted half of the metastatic sarcomas (48 cases, 50.5%) followed by synovial sarcoma (16 cases, 16.8%) and high grade spindle cell sarcoma-NOS (10 cases, 10.5%). The histology of primary and the metastases was similar in 60% of cases of osteosarcoma. Conclusions: Osteosarcoma is the commonest metastatic sarcoma to the lung. There is often a change to fibroblastic histology in patients of conventional osteosarcoma treated with chemotherapy.
Keywords: Chemotherapy, histology, lung, metastasis, metastatectomy, osteosarcoma, sarcoma, synovial sarcoma
|How to cite this article:|
Krishnamoorthy N, Desai S S, Rekhi B, Jambhekar N A. A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs. Indian J Cancer 2011;48:335-8
|How to cite this URL:|
Krishnamoorthy N, Desai S S, Rekhi B, Jambhekar N A. A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs. Indian J Cancer [serial online] 2011 [cited 2020 Jan 21];48:335-8. Available from: http://www.indianjcancer.com/text.asp?2011/48/3/335/84942
| » Introduction|| |
The lung is the most common site for metastasis of all malignant tumors including sarcomas, with the exception of those which are drained by the portal venous system.  Approximately, 20% of the patients with extremity sarcomas will develop isolated pulmonary metastatic disease at some point in the course of their disease.  The development of pulmonary metastasis is a factor of very poor prognosis and the majority of untreated patients die within 6 months of diagnosis.  Early resection of metastatic tumor in soft tissue sarcoma markedly improves survival with the three-year survival rate reaching 46%.  In metastatic osteosarcomas, the association of multi-agent chemotherapy and surgery has improved the five-year survival rate to 70%.  Histological confirmation of these metastasis is vital as it significantly affects the outcome of treatment and prognosis. There are very few large studies histologically documenting the pulmonary metastasis with hardly any articles comparing the histology of the primary and the metastasis.  Herein, the clinico-morphological details of 96 pulmonary metastases are being documented.
| » Aims and Objectives|| |
To histologically review all resected metastatic sarcomas to lung and compare with the primary tumor wherever available.
| » Materials and Methods|| |
The pathology archives of eight years spanning 2002-2009 were searched for pulmonary metastases of sarcoma from soft tissue and bone. A total of 120 cases were identified, but complete clinical data was available in only 95 cases and these have been included in this study. The clinical features regarding age, sex, site of primary tumor was abstracted from the files. As regards metastases, the laterality (unilateral/bilateral), number (solitary /multiple), time interval between primary and metastasis, and details of treatment were also abstracted for all 95 cases.
All histological material in the form of slides and paraffin blocks were retrieved. The lung lesions were evaluated for morphological type of the sarcoma, chemotherapy-related changes, and changes in the adjacent lung tissue. The features were compared with the primary tumor in 20 cases where available. The histological confirmation was based on metastatectomy in 91 cases and on tru-cut biopsy in four cases.
| » Observations and Results|| |
The 95 patients with histologically confirmed pulmonary metastatic sarcoma had a mean age of 29 years (range 6-69). There were 70 males (73.6%) and 25 females (26.3%). Of these, 13 patients (13.6%) were less than 15 years. The mean interval between the commencement of treatment of primary tumor and pulmonary metastasis was 16 months for all the histological subtypes (range - 2 months to 58 months).
The primary tumor was in the lower extremity in 72 cases (74.4%), upper extremity in 15 (15.7%), chest wall/breast in four (4.2%), and one case each from testis, neck, groin, and kidney (~1% respectively). At surgery, the metastatic lesions were found to be unilateral in 69 cases (72.6%) and bilateral in 26 cases (27.3%). The deposits were solitary in 42 (44.2%) and multiple in 53 (55.7%). When unilateral, the metastasis was solitary in 42 cases (60.2%) and multiple in 27 (39.7%). When multiple they were confined to one side in 50.9% and both sides in 49.1%. Histologically, the 95 cases were classified as 48 cases (50.5%) of osteosarcoma and 47 cases (49.5%) of sarcomas "other than osteosarcoma".
The mean age of patients with osteosarcomas was 20 years (range 6 -56 years) [Table 1]. Of these, eleven patients (22.9%) were less than 15 years of age. The primary site was the lower extremity in 42 (87.5%), upper extremity in five (10.4%), and the chest wall in one case (2%). The metastatic tumor was of osteoblastic type in 34 cases (70.8%) [Figure 1], fibroblastic in seven (14.5%) [Figure 2], chondroblastic in five (8%), and telangiectatic in one (1%). One case had no viable tumor; the primary of which was of osteoblastic type. Numerous osteoclast-like giant cells were seen in four cases. All cases of osteosarcomas had received chemotherapy. In 42 cases (87.5%), chemotherapy-related changes like necrosis, hyalinization, and dense sclerotic bone were noted [Figure 3]a and b. Empty turtle shell pattern of osteoid was appreciated in one case. Four cases (8.3%) had a pleomorphic look with osteoid formation, and the remaining two (4%) had a high grade fibroblastic appearance. The percentage necrosis ranged from 10% to 100%.
|Figure 3: Chemotherapy-related changes in osteosarcoma, (a) Necrosis, (b) Dense sclerotic bone|
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|Table 1: Distribution of age, sex, laterality, multiplicity of the most common pulmonary metastatic sarcomas|
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The second group of 47 cases of sarcomas "other than osteosarcoma" comprised 16 synovial sarcoma (16.8%) [Figure 4], 10 high grade spindle cell sarcoma NOS - 10 (10.5%), three malignant peripheral nerve sheath tumor (3.1%), three liposarcoma (two pleomorphic and one dedifferentiated) (3.1%), three Ewing sarcoma/PNET (3.1%) [Figure 5], two malignant fibrous histiocytoma (2.1%), two stromal sarcoma of breast (2.1%), two chondrosarcoma (2.1%), two leiomyosarcoma (2.1%), and one case each of metastatic lesions of rhabdomyosarcoma, epithelioid sarcoma, alveolar soft part sarcoma, and mesenchymal chondrosarcoma (1%). The 16 synovial sarcomas comprised 15 monophasic and one biphasic tumor. Only two synovial sarcomas were of poorly differentiated type.
The adjacent lung tissue showed non-specific interstitial pneumonia in three (3.1%), silicotic nodule in two (2.1%) and non-necrotizing epithelioid granulomas in one case (1%). Non-specific changes like congestion, hemorrhage were noted in eight cases (8.4%).
The histology of the primary tumor and metastasis was available for comparison in 20 cases all of which were osteosarcomas. The histology of the primary and metastases was identical in 12 cases (60%) of which 10 (50%) were osteoblastic and two (10%) were chondroblastic. In the remaining eight cases (40%), the histology of primary and the metastases differed. In four cases (20%), the primary was of osteoblastic type, but the metastases was fibroblastic in three and the last case was predominantly necrotic. In the remaining four cases, the tumor was chondroblastic type at the primary site, whereas the metastasis was osteoblastic in three and fibroblastic in one.
| » Discussion|| |
The lungs are a common site for metastasis of sarcoma especially those arising in the extremities. , In a study comprising 242 metastatic soft tissue sarcomas by Vezeridis et al.  the lung was involved in 38% cases. The overall mean age of the patients in the present analysis of pulmonary metastases was 29 years, but it was only 20 years in patients with a primary osteosarcoma.The average interval between the commencement of treatment of primary tumor and the diagnosis of metastatic disease was 16 months. An interval of less than one year was an indicator of poor prognosis in pulmonary metastases of soft tissue sarcomas in a study by Billingsley et al.  The lower extremity was overall the commonest site of the primary sarcoma (73.6%) especially with osteosarcoma (87.5%); the femur being the most common site (45.8%). A similar observation was noted by Antunes et al,  who reported that primary tumours of the lower limb as the source for pulmonary metastases in 65% cases of osteosarcomas.
The prognostic significance of the number of metastatic lung and nodules present is controversial. , Some studies have indicated better prognosis when there are three or four nodules , , while another study has not found multiplicity of nodules to be significant.  In the present analysis, solitary pulmonary metastasis was seen in 41 cases (43.7%), whereas they were multiple in 53 cases (56.3%). When multiple they were unilateral in 50.9% and bilateral in 49.1%.There were almost an equal number of patients with less than four metastatic nodules (26 patients, 49.6%) and those with more than four nodules (27 patients, 49.4%). The follow-up however was inadequate to gauge its impact on prognosis.
Histologically, osteosarcoma was the commonest metastatic sarcoma comprising half of the cases (48 cases, 50.5%) followed by synovial sarcoma (16.8%) and high grade spindle cell sarcoma -NOS (10.6%). In contrast, a study by Songur et al. revealed malignant fibrous histiocytoma (22.2%), osteosarcoma (18.8%), and liposarcoma (15.5%) as the three commonest metastatic pulmonary lesions.  In another study amongst soft tissue sarcoma, leiomyosarcoma was the commonest (21%) type followed by malignant fibrous histiocytoma (18%), liposarcoma (12%) and synovial sarcoma (14%). 
Previous studies have not demonstrated a relationship between histology of the metastatic lesion and outcome although some have shown a poor prognosis with liposarcoma (median survival 9.8 months). 
In the present study of the 20 post chemotherapy resected pulmonary metastases, two thirds (12 out of 20, 60%) had identical histology to the primary, whereas in seven, the histology was different and the last case was totally necrotic. The histological change in primary and metastases in the seven cases was from osteoblastic to fibroblastic in three cases, chondroblastic to osteoblastic in three cases, and chondroblastic to fibroblastic in one case. This alteration can be ascribed to differentiation due to chemotherapy. However, in a study by Dehner and Dunn  where patients did not receive any chemotherapy, although the histology of the primary and the metastases was identical in 66%, the metastatic lesion were less differentiated in 12% and surprisingly in 18% of cases the metastases revealed abundant osteoid and was more differentiated.
| » Conclusion|| |
Osteosarcomas are the commonest metastatic sarcoma to lung and although the primary and metastases have similar histology in two thirds, in the remainder of cases the histology can be different comprising only fibrosarcoma-like component.
Synovial sarcomas are the other common pulmonary metastatic sarcomas in young adults.
Histological confirmation is essential for proper management and follow-up of sarcomas metastatic to lungs.
| » References|| |
|1.||Willis RA. The spread of tumors in human body, 3 rd ed. London: Butterworth;1973:167-74. |
|2.||Gadd MA, Casper ES, Woodruff JM, McCormack PM, Brennan MF. Development and treatment of pulmonary metastases in adult patients with extremity soft tissue sarcoma. Ann Surg 1993;218:705-12. |
|3.||Antunes M, Bernardo J, Salete M, Prieto D, Eugenio L, Tavares P. Excision of pulmonary metastases of osteogenic sarcoma of the limbs. Eur J Cardiothorac Surg 1999;15:592-96. |
|4.||Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF. Pulmonary Metastases From Soft Tissue Sarcoma-Analysis of Patterns of Disease and Post metastases Survival. Ann Surg1999;229:602-12. |
|5.||Dunn D, Dehner LP. Metastatic osteosarcoma to lung: A clinicopathologic study of surgical biopsies and resections. Cancer 1977;40:3054-64. |
|6.||Robinson MH, Sheppard M, Moskovic E, Fischer C. Lung metastatectomy in patients with soft tissue sarcomas. Br J Radiol 1994;67:129-35. |
|7.||Vezeridis MP, Moore R, Karakousis CP. Metastatic patterns in soft tissue sarcomas. Arch Surg 1983;118:915-8. |
|8.||Putnam JB Jr, Roth JA, Wesley MN, Johnston MR, Rosenberg SA. Analysis of prognostic factors in patients undergoing resection of pulmonary metastases for soft tissue sarcomas. J Thorac Cardiovasc Surg 1984;87:260-8. |
|9.||Casson AG, Putnam JB, Natarajan G, Johnston DA, Mountain C, McMurtrey M, et al. Five year survival rate after pulmonary metastatetomy for adult soft tissue sarcoma. Cancer 1992;69:662-8. |
|10.||Songür N, Dinç M, Ozdilekcan C, Eke S, Ok U, Oz M. Analysis of lung metastases in patients with primary extremity sarcoma. Sarcoma 2003;7:63-6. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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