Pulmonary Tumour Embolism Complicating a Case of Leiomyosarcoma

Patient. A case of peripheral leiomyosarcoma presenting with features of pulmonary thromboembolism is described. Discussion. Persistence of the embolus despite triple-armed thrombolytic therapy and the presence of intravascular tumour invasion suggest the rare entity of pulmonary tumour embolism from a leiomyosarcoma.


C ase history
A 73 year-old housewife w ith an 8-w eek history of increasing shortness of breath presented with acute dysp noea and collapse one week follow ing tru-cut biopsy of a hard, ® xed 20 cm 3 10 cm swelling of the adductor com partm ent of the left leg. T his was a leiom yosarcom a w hich had been slowly enlarging over the previous 2 years. O n examination she was unwell and dyspnoeic w ith a respiratory rate of 33 per m inute. She w as in sinus rhythm 74 beats per m inute, blood pressure 100/50, raised JV P of 10 cm . She had a right sternal heave and a loud P2 on auscultation. T here was hepatom egaly.
Chest radiograph was norm al and oxygen saturation on air 82% . ECG showed right bundle branch block, right axis deviation, inverted T waves in leads V1 to V3, Q w ave and inverted T wave in lead III and S w ave in lead 1.
An IVC ® lter was inserted and pulm onary angiography perform ed. This demonstrated bilateral em boli with a large embolus occluding the left inferior pulm onary artery (see Fig. 1).
A 5F Berenstein catheter was placed at the origin of this artery via a fem oral approach and 5 m g of recom binant tissue plasm inogen activator (rtPA) w as infused as a bolus followed by l mg/hour over the next 24 hours. Angiograms at 6 hours and 24 hours (see Fig. 2) showed no change and therefore the rtPA was stopped, although system ic heparinisation was continued for the next 4 weeks.
V/Q scan con® rm ed bilateral gross perfusion defects with sparing of the left apical region and norm al ventilation pro® le. C onsecutive echo-cardiogram s demonstrated a dilated right ventricle with reversed septal m otion and dilated right atrium. T he pulmonary artery pressure was 74 m m Hg. This failed to im prove, as did her oxygen saturation on  air varying from 82% to 86% . D oppler ultrasound scan of the deep venous system of the leg was negative. Four weeks after presentation a w ide excision of the tum our was perform ed under general anaesthetic. At operation the surrounding super® cial and deep veins w ere ® lled with tum our extending proxim ally into the fem oral veins. As m uch as possible of this tum our w as retrieved using a F ogarty catheter. T he content of the veins was proven by histology to be leiom yosarcoma and no signi® cant throm bus was found.
Histological exam ination demonstrated wellcircum scribed nodules of focally m yxoid spindle cell sarcom a com posed of fusifo rm cells with bluntended hyperchromatic nucleii and eosinophilic cytoplasm . The app earance was consistent with a diagnosis of leiom yosarcom a of intermediate grade.
M any of the tum our lobules were growing within the vessels.
Excision was com plete but unfortunately the patient died 5 w eeks later without im provem ent in her cardiovascular status and post-m ortem exam ination was refused.

D iscussion
T he patient presented with clinical and radiological features of recurrent m assive pulm onary thromboembolism . T he evidence is indirect but we suggest that the pathophysiology in this case was pulmonary tumour embolism from the peripheral leiom yosarcom a.
The em bolus w as totally refractory to the triplearm ed therapy com prising an IV C ® lter; infusion of 29 m g rtPA/24 hours directly on to the site of the m ain perfusion defect; 4 weeks system ic heparinisation. T he ef® ciency of this regimen in the m anagem ent of pulm onary embolism has been veri® ed by G oldhaber et al. 1 who reported clot lysis in 34 of 36 patients treated with rtPA only using up to 90 m g over 6 hours infused peripherally. A lower dose was used in the presented case but was selectively adm inistered to the site of obstruction. Rosenthal et al. 2 use a sim ilar triple-arm ed protocol and found rtPA showed a m ore rapid im provem ent compared with streptokinase. W interbauer et al. 3 conducted a retrospective analysis using clinical records and post-m ortem ® ndings of 366 cases of renal cell carcinoma, hepatocellular carcinom a, choriocarcinom a, gastric and breast carcinom a and found an incidence of pulm onary tum our embolism of 26% with clinically signi® cant emboli of 8.3% . Renal cell tum our, hepatocellular carcinom a and choriocarcinom a characteristically invade m ajor vessels. H epatic m etastases app eared im portant in the incidence of pulm onary tum our em bolism of gastric and breast carcinom a doubling the incidence in the form er (23% compared with 10%) and trebling the incidence in the latter (27.5% compared w ith 11%). T he authors (3) argue that the frequency of invasion of the central and sm all hepatic veins in these m etastases accounts for this difference. This illustrates tw o points: that pulm onary tum our embolism occurs m ore frequently than is clinically recognised and is m ore com m on in tum ours that invade veins. The ® ndings of m acroscopic venous invasion at operation and histological con® rm ation of intravascular leiom yosarcom a emboli therefore supports pulm onary tum our em bolism as the pathophysiology in this case. An alternative explanation for pulm onary tum our embolism in our patient is that the leiom yosarcom a arose from the vein wall and extended into the surrounding soft tissue rather than the other way round. Leiomyosarcom as are generally locally invasive and tend to com press rather than invade m ajor vessels, unless they arise from the vessel walls. Relatively few of the low-grade tum ours m etastasize; about 50% of the high-grade tumours w ill do so. In this case w e assu me m etastasis is by m icroembolisation rather than by extensive tumour perm eation. A literature search identi® ed four cases which presented with features of pulmonary em bolus but were subsequently identi® ed as leiomyosarcom as arising from the pulm onary arteries them selves (Schlecht et al., 4 Reinbold et al., 5 M adu et al. 6 and Prom isloff et al. 7 Arbeit et al. 8 described a case in w hich an extensive retroperitoneal leiomyosarcom a with anaplastic elements invading the inferior vena cava w as presum ed to have embolised during surgical excision. There were no clinical features of pulm onary embolisation post-operatively and investigations w ere norm al until 16 months later when, despite prophylactic chemotherapy and radiotherapy, a right hilar m ass, identi® ed as leiom yosarcom a, developed. The patient died 4 m onths later after pneum onectom y w ith widespread m etastases. D em oulin et al. 9 described a case of leiom yosarcom a arising from the inferior vena cava and extending from 10 cm below the renal vessels along the entire length of the inferior vena cava with extension into the right atrium , ventricle and pulm onary infundibulum w hich presented with features of pul-m onary em bolism . Although tumour fragm ents were found in the peripheral branches of the pulm onary arteries at post-m ortem the patient had previously undergone a T rendelenburg operation and required intraoperative de® brillation which m ay have fragm ented the tum our. The preoperative features of pulm onary embolism m ay have been caused by tumour extension rather than true embolisation. W hat is unusual, though not unique, about this case is the extensive perm eation of tum our throughout the venous system which resulted in m acroscopic tum our em bolisation into the pulm onary arterial tree.
In cases of established neoplasia it m ay be worth considering intralum inal biopsy at the time of angiography if a large pulm onary em bolus is refractory to direct throm bolysis.