Leiomyosarcoma of the pulmonary artery masquerading as disseminated tuberculosis

1. Case report 

A 66-year-old retired lorry driver was investigated by chest physicians because of a left upper lobe cavitating lesion and back pain. His history was remarkable for a left lower lobectomy aged 18 for bronchiectasis, thought secondary to TB, from which his mother had died. He was an independent ex-smoker of forty pack years with no travel history outside the UK. Bronchoscopy to investigate his cavitating lesion was unremarkable, with samples being negative for bacterial culture and acid-fast bacilli. He was treated empirically with rifampicin, isoniazid and pyrazinamide with radiological improvement at six months.

One year later he re-presented with weight loss, night sweats, haemoptysis and back pain. A CT scan revealed a new right upper lobe cavity and scarring in the left upper lobe. An MRI scan was reported as showing lesions compatible with TB at L2 and S2. Sputum smears and serum ANCA were negative, bronchoscopic washings were negative for TB on direct smear and culture and conventional antibiotics were unhelpful. He was treated as reactivated TB with rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin. Clinical and radiographic improvement was seen again after one month in keeping with the presumptive diagnosis.

After two months of treatment he presented to a second hospital with a collapse and a two-week history of worsening back pain, dyspnoea and haemoptysis. CXR showed cavitating lesions in both upper zones. MRI showed persisting and new lytic lesions in several vertebral bodies most marked at L2 (Fig. 1). CT guided and subsequent open biopsies of L2 were undertaken but were non-diagnostic. There was no growth on either standard or TB culture and TB PCR was negative. Despite this anti-tuberculous chemotherapy was continued.

View Large Image Download to PowerPoint

Fig. 1 T1 weighted sagittal MRI of the spine demonstrating multi-level disease. With permission from Weston General Hospital, UK.

He re-presented after five months of treatment with fevers and worsening back pain. MRI revealed new spinal lesions. CT now showed multiple cavitating lung lesions (Fig. 2). Bronchoscopy, trans-bronchial biopsies and bronchoalveolar lavage were unremarkable, all laboratory tests for TB were negative. Repeat open vertebral biopsies demonstrated non-specific inflammation, bone culture and mantoux testing were negative. In the absence of clinical improvement or positive microbiology all anti-tuberculous medications were stopped, after a total of six months.

View Large Image Download to PowerPoint

Fig. 2 CT chest demonstrating cavitating lesions and loss of volume on the left. With permission from Weston General Hospital, UK.

Reassessment that week revealed a new systolic murmur and echocardiography demonstrated severe pulmonary hypertension. A CT pulmonary angiogram (CTPA) was negative for pulmonary embolus but the left upper lobe artery now appeared narrowed. There was a suggestion of abnormal soft tissue at the left hilum with progression of bony lesions and pulmonary cavities.

A trial of systemic steroids was initiated with improvement in pain and mobility permitting transfer to a spinal unit at a third hospital for stabilisation of L2.

At the spinal unit he developed left sided pleuritic chest pain. A CTPA showed that several of the pulmonary cavities were associated with thrombosed pulmonary vessels and that the left pulmonary artery appeared totally occluded (Fig. 3). Gadolinium enhanced MRI implied that this was due to thrombus rather than tumour. Additionally there were destructive bone lesions at multiple new sites (Fig. 4). Within days he succumbed to overwhelming respiratory sepsis, four years after his initial presentation.

View Large Image Download to PowerPoint

Fig. 3 CTPA demonstrating occlusion of the left pulmonary artery. With permission from North Bristol NHS Trust, UK.

View Large Image Download to PowerPoint

Fig. 4 T1 weighted sagittal MRI of the spine demonstrating progression of disease and collapse of L2. With permission from North Bristol NHS Trust, UK.

Post-mortem examination confirmed the left pulmonary artery to be occluded by old thrombus. There was dense fibrotic tissue involving the left pulmonary artery and evidence of cavitating infarction in both upper lobes with multifocal disease in the vertebral column. The right lung showed widespread pneumonic change of recent onset.

Histology from the left hilum and bony lesions was identical showing a spindle cell neoplastic lesion with a prominent storiform pattern. Immunohistochemical staining was positive for vimentin and smooth muscle actin and negative for cytokeratins, macrophage markers, CD99 and CD34. A diagnosis of pulmonary artery leiomyosarcoma (PA-LMS) with spinal metastases was made.

2. Discussion 

Leiomyosarcoma (LMS) is from a histologically diverse group of pulmonary artery sarcomas (PAS). It remains notoriously difficult to diagnose and although rare is the commonest primary pulmonary artery malignancy. Here we will discuss the condition with an emphasis on features which may hasten its diagnosis.

First described in 1923 by Mandelstramm, pulmonary artery sarcomas are thought to arise from pleuripotent cells found in the intima of the vessel. Because of its mesenchymal origins LMS is reported as arising within tissues as disparate as the testis1 and tongue2 which along with its propensity to cause systemic features, explains why it may be regarded as a great mimic.

The aetiology of leiomyosarcomas remains unclear. However malignant fibrous histiocytoma (MFH, one of the pulmonary artery sarcomas) is known to occur in areas of chronic inflammation such as gouty tophi3 at the site of internal fixation of fractures4 and at the site of chronic infection.5, 6 Takanami et al. report a latent period of sixteen years between pleuropneumonectomy and the diagnosis of MFH.7 It is therefore noteworthy that our patient had a history of thoracic surgery in the form of a left lower lobectomy, the same side as he later developed PAS.

An infective aetiology has also been postulated with a case of PA-LMS reported with the tumour itself expressing the Epstein Barr virus some years after symptomatic EBV infection in an immunocompetent individual.8

PAS usually affect adults within the age range of 45–64. Symptoms are largely related to the pathophysiology of the tumour which causes increasing disruption to the right ventricular outflow tract (RVOT). Patients most often present with exertional dyspnoea, but chest pain, cough, weight loss and haemoptysis are also seen.11 Syncope suggests significant compromise of the RVOT; chest pain and haemoptysis may be due to metastatic emboli (seen in approximately two thirds of cases9) or local invasion into an airway. Around half of PAS cases show transmural spread into the surrounding lung parenchyma, airways or lymph nodes.9 Tumour embolism may cause pulmonary infarction and result in fever and later cavitating disease. Presentation may not occur until there is significant occlusion of the pulmonary vasculature.10

Systemic metastases are found in 20%9 of cases and have previously been described at sites including the liver, pancreas, mesentery, brain, adrenals, kidneys, thyroid and the skin.11 To our knowledge our case of PA-LMS metastasising to the spine is unique. Bony deposits with PA-LMS are rare, our search revealed only two cases in the English literature, one involving the hip12 with the other site being unspecified.13

Laboratory findings are seldom helpful. Patients often have markers of systemic upset generally not seen in pulmonary embolus, with which they are erroneously diagnosed in more than half of cases.9 Laboratory features of chronic inflammation implicate a myriad of other conditions. There have however been case reports of leiomyosarcoma where these have been prominent and have resolved after excision of the tumour14 in keeping with a paraneoplastic phenomenon. The possible secretion of adrenaline-like substances from a PAS has also been reported with the patient presenting as if with phaeochromocytoma.15

Other reported misdiagnoses are pulmonary artery stenosis, extrinsic compression by bronchial tumour or mediastinal mass.9, 11

The clinical presentation of PA-LMS may be indistinguishable from that of pulmonary TB. Both conditions can incite a systemic inflammatory response with cavitating lung disease, which in the case of PA-LMS is due to pulmonary infarction. This dilemma has previously been reported with the patient being treated for TB on the basis of clinical suspicion alone.16 In our case the known exposure to TB and apparent improvement on anti-tuberculous treatment fuelled the pursuit of this diagnosis.

Chest x-rays may be normal or may show a hilar mass, pulmonary nodules or infiltrates, cardiomegaly, PA prominence, pleural effusion or oligaemic lung fields.

ECG may demonstrate right ventricular strain. Similarly echocardiogram may reveal elevated PA pressures and in some cases may delineate the tumour itself. Trans-oesophageal echo offers superior images of the pulmonary trunk and artery and so gives a greater chance of visualising the tumour.

As discussed PAS may be difficult to differentiate from the more frequently encountered PE. Distinguishing between these diagnoses is challenging; both may embolise distally or indeed co-exist where a vessel is narrowed by LMS. CT scanning is helpful in so far as it may show local invasion of the tumour or its metastases.13 However it cannot discriminate between tumour and thrombus in the PA. MRI with gallium based contrast media to achieve this was described as early as 1976.17 Tumour within the PA enhances with this technique.10, 18 Additionally tumour (but not thrombus) shows uptake on FDG-PET scanning.9 Angiography may show an intraluminal lobulated tumour which when pedunculated has been described as having a “to-and-fro” movement with each cardiac contraction.9, 11, 18

Ventilation-perfusion scanning offers little to allow differentiation between tumour and embolus. It is noteworthy however that perfusion deficits secondary to PAS will remain unchanged over time despite adequate anticoagulation11, 12, 13 and that large unilateral perfusion defects are uncommon in PE.19 Failure to improve despite adequate anticoagulation, with no clear risks for VTE and no evidence of DVT should raise the possibility of an alternative diagnosis.

Although surgery offers the only known means of cure, many cases are found intra-operatively to be unresectable. A high index of suspicion and a careful search for metastases may prevent inappropriate procedures and allow palliation. Potential surgical interventions include pneumonectomy, pulmonary endarterectomy and resection with PA reconstruction. Kaplan–Meier survival curves suggest a mean survival of 1.5 months after diagnosis, Parish et al. report a series with one case surviving 3.5 years after diagnosis.11 Surgical intervention (largely to ameliorate haemodynamic compromise) extends the median survival to 10 months.13 Death is usually related to RVOT compromise and RV dysfunction.

The role of chemotherapy remains unclear. Diagnosis is usually too late for it to be effective, and the rarity of the condition makes its evaluation far from straight forward.

Our unique case illustrates the diagnostic difficulties associated with pulmonary artery sarcomas as well as the way its presentation can overlap with that of pulmonary TB.

Conflict of interest Statement 

Angela Atalla, Sarah Bennett, David Smith have no conflict of interest.