r THE INSTITUTE OF ONCOLOGY, LJUBLJANA 7 RADIOLOGIC CHARACTERISTICS OF PULMONARY METASTASES FROM DIFFERENT HISTOLOGICAL TYPES OF HUMAN SARCOMAS Klanjscek G, and S. Plesnicar Summary: Pulmonary metastases configuration types were studied in 33 cases with osteogenic sarooma, 35 cases with soft tissue sarooma and 28 cases with malignant malanoma. lit was found that the most frequent dissemination type was characterised by the presence of a limited number of large and medium sized metastatic deposits which was found in 40 out of 96 studied cases. Solitary metastases were found most frequently (9/35 cases) in soft tissue sarcomas, while miliary and submiliary dissemination was characteristic for malignant melanoma cases. In our series in 4 out of 28 cases a miliary dissemination was ascertained. Medium and small sized metastases appeared in an almost identical proportion in osteogenic sarcoma (6/33 cases) and soft tissue sarcoma (5/35 cases), and was not observed in cases with malignant malanoma. Pleural effusion seems to appear in cases with metastases situated on the periphery of lung parenchyma. UDK: 616-006.3.04-06:616.24-006.04-033.2-073.75 Key words: radiologic characteristics, pulmonary metastases, human sarcomas Radiol. lugosl., 12; 615-620, 1978 L J Introduction. — The contributions on radiologic appearance of pulmonary metastases originating from human sarcomas of different histological types published so far have shown that differences in their characteristics, such as the size and number, may exist. Therefore a systematic description and characterization of pulmonary metastases from different types of sarcomas may reveal that they appear in different configuration types, which may be present, far instance, in preponderance among cases with a known histological type of sarcoma. The majority of studies on pulmonary metastases from malignant tumors, published in recent years are concerned with their growth characteristics, therefare differences in their radiologic appearance are reported sporadically. In a study (Cohen et al. 1974) the value of the scanning procedure with Sr-85 was compared with the radiologic appearance of the pathological changes observed in a patient with osteogenic sarcoma. It was noted that the pulmonary metastases were numerous and characteristically ossifying. In connection with this, the authors believe that radiologic examination is a superior method far detection and evaluation of pulmonary metastases. Similarly, the radiologic appearance of pulmonary metastases was also described in seven cases with pulmonary metastases originating from osteogenic sarcomas where a study of the Gompertzian type of growth was carried out (Miller 1976). Radiologic characteristics of pulmonary metastases were reported in a comparative study where differences were noted when comparing the radiologic appearance of pulmonary metastases originating from fi-brosarcoma case to those from osteogenic sarcoma cases. Pulmonary metastases from fibrosarco-ma were faund to be less numerous and their onset after primary treatment was delayed, a fact which could contribute to 2* 616 Klanjscek G. and S. Plesnicar a longer average survival. It was noted also, that longer survival periods were in relation to the histological differentiation of the primary tumor; the more differentiated tumor grows at a slower rate (Jefree and Price 1976). Differences in the metastatic appearances were reported in a series of seven cases with fibroxanthoma of the soft tissue. Metastatic deposits were found in mediastinal lymph nodes, kidneys, bones, in pleural cavity but preferentially, that is in five out of seven cases, in the lungs. In two cases solitary and in three cases multiple metastatic deposits were diagnosed in the lungs. Regardless their size the metastases were characterized by a fast growth rate. (Burgener and Landmann 1976.) Similar variations in the radiologic appearance, that is in the size and number of pulmonary metastases, were observed also in previous studies of growth characteristics of pulmonary metastases, reported elsewhere (Plesnicar et al. 1976, Plesnicar et al. 1978). Therefore, the purpose of the present communication is to ascertain possible existing differences in the number, size, distribution patterns and interrelationship, in the radiologic appearance of pulmonary metastases from different types of human sarcomas. Far this study, caes with pulmonary metastases from osteogenic sarcomas and malignant melanoma were considered. Material and methods. — Patients with pulmonary metastases originating from three different sarcomas were included into the study. Consequently the lung radiographs were studied in 33 cases with osteogenic sarcoma, 35 cases with soft tissue sarcomas and 28 cases with malignant melanoma. Altogether, 96 patients with pulmonary metastases from the three types of sarcomas were studied. The antero-posterior radiographs were taken on »Stratomatic-CGR« diagnostic x-ray machine et a standard 150 cm fo-kus-skin distance and with tube voltage being 150 kV. In the study were included cases with histologically confirmed primary sarcoma, not previously treated by chemo- or radiotherapy. OB O..;,-, Q) Cu bD P (j) Q 'E QJ 2 o n cj gad 0 5 z CJ U) Ctl 0 oj (fJ (Number of cases) Large sized, solitary Large and medium ,sized, limited lin number 1 2 3 14 9 12 2 14 Medium and small sized, numerous 3 6 5 1 Nodular, large number 4 o o 2 Miliary dissemination 5 o o 4 Ossifying metastases 6 3 o o Mediastinal lymph nodes metastases 7 o 4 o Pleural effusion 8 7 5 o Table — Distribution and frequency of pulmonary metastases configuration types from 96 patients with sarcomas (33 cases with osteogenic sarcoma, 35 cases with soft tissue sarcomas and 28 cases with malignant melanoma) Results. — According to their morphological and, consequently, 'radiologic .appearance several patterns of pulmonary metastatic growths were identified and subsequently grouped lin the following pulmonary metastases configuration types: 1. large sized, and usually solitary metastases, 2. large and medium sized metastases appearing in limited number, possibly in both lung parenchymas, 3. medium end small sized, numerous ¡metastases appearing ¡in both lungs, Cu ru rn Radiologic characteristics of pulmonary metastases 617 4. nodular or coarse granular metastases appearing in large number on both sides, the so called ¡submiliary type of metastatic dissemination, 5. miliary dissemination, represented by a large number of small sized metastases spread throughout both lung fields, 6. primary ossifying and, ussually, numerous metastases, 7. metastases in the mediastinal -lymph nodes, and 8. pleural effusion. Both last types, ii. e. the metastatic spread in the mediastinal lymph nodes and pleural effusion are reported as they appear often in connection with the metastatic dissemination in the lungs. The frequency and distribution of pulmonary metastases configuration types according to the site are presented in the table. Osteogenic sarcoma. — In the majority of cases, that is in 14 out of 33 patients with pulmonary metastases from osteogenic sarcoma, the seoond type that is large and medium sized metastatic growths were detected (Type 2). The second according to their frequency were six cases with medium and small sized but numerous metastases (Type 3). To the same group belong also three oases with primary ¡ossifying lung metastases (Type 6). Large sized and solitary metastases (Type 1) were found in three cases of the ¡studied group. Pleural effusion was ascertained in seven cases and it always went ¡along with solitary or smaller metastases which were situated along the lung periphery. This was ¡observed more frequently ¡in advanced cases. The submiliary or miliary metastatic dissemination (Type 4 and 5) were not observed in the studied series of patients with osteogenic sarcoma. Solf tissue sarcomas. — In this group, cases with soft tissue sarcomas of diffe- rent histology like fibrosarcomas, rhabdomyosarcomas, leiomyosarcomas and he-manghiopericytoma, liposarcoma and an-giosarcoma were studied. Again in the majority of cases, that ¡is in 12 out of 35 patients large and medium sized metastases were found in a moderate ■number (Type 2), meanwhile the next according to the frequency were in this group large and solitary metastases. These were found in 9 ¡oi.it of 35 cases (Type 1). Medium and small sized metastases in large number (Type 3) were detected in five cases. In ¡one ¡patient the radiologic appearance was characterized by the presence of large and medium ¡sized together with numerous small sized metastases thus presenting a ¡mixed picture of metastatic distribution (Type 2 and 3). Metastatic deposits ;in mediastinal lymph nodes were observed in four cases. In one patient lymph node metastases appeared during the terminal period of disease, after a complete cure by irradiation of a solitary metastatic deposit iin the right lung, which appeared and, was treated months before. Pleural effusion was found iin five cases, and tin all the oases it was an accompanying (phenomenon of the ¡pulmonary metastases. Submiliary or miliary metastatic spread {Type 4 and 5) was not ¡observed among ¡patients of the ¡studied ¡series. Malignant melanoma. — Large and medium sized metastases iin moderate number (Typq 2) weire found iin 14 out of 38 cases with malignant melanoma. .Next according to their frequency were four cases with miliary dissemination (Type 5). In these cases miliary dissemination appeared always combined with other types of metastases or .developed ¡subsequently to the already present metastatic spread of other types. For instance, in two cases miliary dissemination was found together with large ¡and medium sized metastases (Type 2) .and in another two cases combined with the submiliary dissemination (Type 4). The 616 Klanjscek G. and S. Plesnicar subimiiliary dissemination (Type 4) was diagnosed only in two cases, while independent miliary metastatic spread was not observed in the studied series. Wlith the exception of one case submiliary and miliary dissemination of pulmonary metastases (Type 4 and 5) was found to appear 'simultaneously, aiind to distinguish and characterize the dissemination type usually [Present difficulbi.es. Solitary metastases (TY]pe 1) were found in two while medium and small sized metastases (Type 3) were found in one case. The interesting frnding An the studied series was that pleural (effusion was never found iin cases with solitary metastases, whereas large, medium and small sized metastases (Type 2 and 3) were iin our cases -accompanied with pleural effusion. Fmm the presented observation of the metastatic diiss^nination of pulmonary metastases kom osteogenic sarcoma, soft tissue sarcomas and malignant melanoma the following general characteristics, regarding their radiologic appearance can be deduced: 1. The most frequent metastatic dissemination type 'observed in almost equal proportion in all tlnree instances is the appearance of a moderate number of large and medium sized pulmonary metastases (Type 2). 2. Solitary metastases (Type 1) were found most frequently iin cases with soft tissue sarcomas followed by its frequency iin cases with osteogenic sarcoma. 3. Submiliary and miliary dissemination (Type 4 and 5) were found iin patients with malignant melanoma. 4. Numerous, medium and small sized metastases (Type 3) appeared in an almost equal number of patients iin osteogenic sarcoma (6 cases) and soft .tissue sarcomas (5 cases) while they were least frequent in the series of cases with malignant melanoma, probably 'because outweighed by the frequent appearance of submiliary and miliary dissemination. 5. Ossifying metastases were evidently found in cases with osteogenic sarcoma. 6. Mediastmal lymph node metastases were found only in cases with soft tissue sarcomas. 7. Pleural effusion seems to be always accompanying pulmonary metastases and in these series was never observed to appear ¡independently. It appears most frequently in soft tissue sarcomas. Discussion. — In the prese nted work an attempt was made to define the possible existing different pul^mary metastases configuration types in osteogenic sarcoma, soft tissue sarcomas and malignant melanoma. According (to (the presened findmgs the most frequent configuration type of metastatic spread to the lung iiis thart: characterized by the presence of a moderate number of large and medium isized metastatic growths m both lungs. Analysing further on, it was possible to ascertain that different metastatic configuration, types were noted more .frequently in cases with isaft "issue sarcomas, while the miliary dissemination is characteristic for malignant melanoma cases. Medium and small sized metastases appeared in the same frequency :in cases with osteogenic sarcoma and soft tissue sarcomas, while they could not be detected in malignant melanoma patients. Thus lit appears that some of the 'described configuration types tend to he 'associated with a specific type of sarcomatous disease. Accordingly, different therapeutic measures could be foreseen for different configuration types. Since the ,miliary dissemination is the most common final type of metastatic spread tin malignant melanoma cases, it would be national to treat with systemic chemotherapy such patients even in cases where large or medium size metastases are already present. In this way it would be at least possible to delay the ¡appearance of miliary spread which leads the patients 1(o the respiratory insufficiency and consecutive death. However, in Radiologic characteristics of pulmonary metastases 617 -cases with 'solitary metastases which are frequently observed in patients with soft tissue sarcomas ad were not ascertained to lead to miliary dissemination, surgical treatment would be reccomanded. In cases with a moderate number of large and medium sized metastases .appearing relatively frequently in all three types of sarcomas, the possibility of a combination of ■chemotherapy and local, focused irradiation -of predominantly large metastatic deposits demands further ooaisideration. From the-.se briefly mentioned possible applications of therapeutic measures it appears that the •characterization of aanfiiguration types of metastatic spread :ie the lung oould also "have some practical beaming on ithe therapeutic planning. Sa že t a k RENDGENOLOŠKE KARAKTERISTIKE PLUČNIH METASTAZA RAZLIČNIH HISTOLOŠKIH TIPOVA SARKOMA ČOVEKA Na Onkološkom institutu u Ljubljani pro-učavali smo udaljene metastaze u 33 slučaja primarnog osteogenog sarkoma, kod 37 bole-snika sa primarnim sarkomom mekih česti različitih delova tela i različite histologije i kod 30 slučajeva malignog melanoma. Osim u 4 slučaja metastaza u kosti radilo se skoro isključivo o metastazama u plucima, u pleuri i u mediastinumu. Broj naših slučajeva (96) prilično' je visok i nam tirne omogucava ana-lizu različitih tipova metastaziranja u pluca. Svi primarni su tumori histološki potvrdeni. Metastaze u plucima merili smo u njihovom uspravnom (vertikalnom) i vodoravnom (horizontalnem) promeru na snimcima pod jed-nakim tehničkim uslovima i to na rendgen-skim snimcima sa tvrd.im zrakama 150 KV i kod. udaljenosti žarište (fokus) — film 150 cm. U obzir smo uzeli samo slučajeve, kod kojih pluca nisu bila zračena i koji nisu prirnali hemoterapiju. Broj, oblik, veličina i lokalizacija metastaza prikazani su na tabeli. Opis, nazive ras-podelu kao i oznake odnosno karakteristike metastaze morali smo pronaci sami, jer ih u nama pristupačnoj literaturi nismo pronašli. Sa stanovišta rendgenološke morfologije .mozemo metastaze u plucima podeliti na više .grupa i to: a) velike — solitarne b) velike i srednje — malobrojne c) srednje i malene — mnogobrojne d) nodularne (gruba zrna) — jako mnogobrojne — submiliarne e) tipične miliarne f) primarno koštane — mnogobrojne g) metastaze u limfnim čvorovima med.ia-stinuma h) pleuralni izliv. O s te o geni s ark o m je u plucima imao najviše velikih i srednjih — malobrojnih metastaza (14 slučajeva od 33 primera osteogenog sarkoma). Na drugom su mestu bile srednje i malene — mnogobrojne metastaze (6 slučajeva). U ovu grupu ulaze i metastaze, koje su bile primarno koštane — osificirane (3 slučajeva). Solitarne, velike metastaze bile su pronadene samo u 3 slučajeva. Submilijarnih i tipično milijarnih metastaza kod osteogenog sarkoma nismo našli. Pleuralni izliv bio je u 7 slučajeva, ali nikad.a samostalno' — prati-o je uvek periferne metastaze u plucima. Sarkomi m e kliih česti različite histologije (fibrosarkomi, rabdomiosarkomi , lei-omiosarkomi, hemangiopericitomi itd.) daju takoder najviše metastaza iz grupe velikih i srednjih, malobrojnih (12 slučajeva). Odmah iza njih dolaze velike, solitarne metastaze (9 slučajeva). Srednje velikih i malih, mnogo-brojnih metastaza bilo je u plucima kod 5 bolesnika. Submilijarnih i tipično milijarnih metastaza u ovoj grupi sarkoma nismo našli. Pleuralni izliv bio je 5 puta i uvek je pratio metastaze u plucima — nije dakle nastupao samostalno. U limfnim čvorovima mediasti-numa našli smo metastaze kod 4 bolesiJJika. Kod m a 1 i g nog me1 a nom a u plucima bilo je takoder najvliše velikih i srednjih — malobrojnih metastaza (14 slučajeva) — isto kao i kod osteogenog sarkoma. Na drugom su pak mestu tipične miliarne metastaze, koje su u ovirn slučajevima nastupile zajedno sa drugim tipovima metastaza ili su došle posle njih (2 puta nastupaju zajedno sa velikima i malobrojnima, a 2 puta zajedno sa submill-jarnima). Submilijarne samostalne metastaze viideli smo samo 2 puta, dok samostalnih tipičnih milijarnih metastaza uopšte nije bilo. Submilijarne i tipično milijarne metastaze nije bilo. Submilijarne i tipično milijarne metastaze nastupaju obično zajedno (4) i teško ih je medusobno razlikovati. Velike, solitarne metastaze videli smo u 2 slučaja. Pleuralni izliv je uvek pratio velike, srednje i malene — malobrojne i brojne metastaze, dok ga kod solitarnih metastaza nismo zapazili, što je ne-obiCno i bas obrnuto kao kod osteogenog sarkoma Nadamo se, da smo našom ocenom rendgen-ske morfologije pomogli kod. razjašnjavanja 616 Klanjscek G. and S. Plesnicar važnog pitanja plucnih metastaza kod razli-oitih vrsta sarkoma, što može biti -od pomoci prilikom donošenja odluka o eventualnom načinu terapije metastaza — pre svega soli-tarnih — u plucima. Literatura 1. Burgener F. A., S. Landmann: Die Ri:int-genmanifestation des Fibroxantbosarkoms. Fortschr. Roentgenstr. 125, 123-129, 1976. 2. Cohen Y., G. Brook, J. D. Sobel, L. Auslander: 85Sr uptake in lung metastases of osteogenic sarcoma. Oncology 30, 493—498, 1974, 3. Jeffree G. M., C. H. D. Price: Metastatic spread of fibrosarcoma of bone. A report on forty