Association of non-traumatic complex regional pain syndrome with adenocarcinoma lung on 99mTc-MDP bone scan

INTRODUCTION

Complex regional pain syndrome (CRPS) or reflex sympathetic dystrophy (RSD) is an excessive or exaggerated response to an injury of an extremity manifested by (a) intense/unduly prolonged pain (b) vasomotor disturbances (c) delayed functional recovery (d) associated trophic changes.[1] CRPS typically occurs after an inciting event like trauma, surgery etc., However, in 10-26% cases no identifiable cause can be found. Other suspected inciting factors include cerebrovascular accidents, myocardial infarction, medicines including anticonvulsants, barbiturates, diseases of cervical spine, neuromuscular disorders etc.[2] Criteria have been set by Kozin et al.[3] and Mackinnon and Holder[45] for interpretation of bone scan findings and are widely followed.

CASE REPORT

A 56-year-old male, smoker since last 30 years presented to the physician with complaints of cough and hemoptysis since 3 weeks. A chest radiograph showed a right lung upper zone mass with surrounding consolidation [Figure 1]. There was no bone destruction. Non-contrast computed tomography scan of the chest showed a homogeneous mass with lobulated margins and surrounding consolidation in the right upper lobe. There was no calcification or cavitation seen in the mass. Mass showed a broad area of contact with the anterior chest wall, superior vena cava, and right brachiocephalic vein. No rib destruction or brachial plexus involvement were noted. Mass was not extending in to the paravertebral location where the stellate ganglion is located. There was no significant mediastinal adenopathy or lung metastasis seen [Figure 2]. A tru-cut biopsy revealed adenocarcinoma lung. The patient was referred for a bone scan to rule out metastases. The Nuclear Medicine physician observed swelling and redness in the right hand of the patient. The patient underwent a three phase 99mTc-MDP bone scan with intravenous administration of 20 mCi (740 MBq) radiotracer. Flow and pool phase study revealed diffusely increased tracer activity in the right hand and elbow [Figure 3]. Whole body anterior and posterior views taken 3 h later showed no evidence of metastases but right wrist joint and hand showed diffusely increased juxta-articular uptake consistent with CRPS. Also noted was increased uptake along long bones of the lower limbs especially in the tibiae, consistent with hypertrophic osteoarthropathy (HPOA) [Figure 4]. A radiograph of bilateral hands showed juxta-articular osteopenia consistent with CRPS and there was increased soft-tissue shadow in the right hand suggestive of subcutaneous edema. There was also periosteal reaction seen in the distal radius and ulna suggestive of HPOA [Figure 5]. Seven days after the diagnosis on bone scan, the patient developed pain in the affected hand. He was prescribed NSAIDS for these symptoms which did not relieve his symptoms appreciably. The patient was referred to the pain clinic of our institution for further management in addition to his oncologic treatment.

Close

Figure 1 Chest radiograph PA view shows a mass lesion (thick arrow) seen in the right upper zone with surrounding consolidation. No obvious bone destruction seen. There are no other nodules seen in bilateral lung fields. Bilateral cardiophrenic angles are free

Export to PPT

Close

Figure 2 (a,b) Non-contrast computed tomography scan of thorax in mediastinal (a) and lung window (b) show homogeneous lobulated mass lesion seen in right upper lobe with wide area of contact with chest wall and mediastinal vessels. No calcification or cavitation seen in the mass. The location of stellate ganglion in the paravertebral location (thick arrow) is free from the mass. There is surrounding consolidation (*) seen in the right upper lobe

Export to PPT

Close

Figure 3 (a,b) PA radiograph of bilateral hands with wrists (a) and cropped image of distal radius and ulna (b) show juxta-articular osteopenia (thick arrow) in bilateral hands along with increased soft-tissue in the right hand. There is also periosteal reaction seen in the distal shaft of right radius and ulna (thin arrow). These findings along with clinical features are suggestive of reflex sympathetic dystrophy with hypertrophic osteoarthropathy

Export to PPT

Close

Figure 4a Flow phase images of both hands after injection of 20mCi 99mTc-MDP reveals increased flow to the right hand

Export to PPT

Close

Figure 4 (b,c) Anterior and posterior pool phase images of both hands after injection of 20mCi 99mTc-MDP reveals increased pool activity in the right wrist and hand

Export to PPT

Close

Figure 4 (d,e) Anterior and posterior pool phase images of both hands after injection of 20mCi 99mTc-MDP reveals increased pool activity in the right elbow

Export to PPT

Close

Figure 5a Delayed whole body image after injection of 20mCi 99mTc-MDP reveals no evidence of metastases but increased juxta-articular uptake in the right wrist and small joints of right hand consistent with reflex sympathetic dystrophy

Export to PPT

Close

Figure 5b Delayed spot view after injection of 20mCi 99mTc-MDP reveals increased juxt-aarticular uptake in the right wrist and small joints of right hand consistent with reflex sympathetic dystrophy

Export to PPT

DISCUSSION

Since CRPS/RSD lacks specific histopathologic or biochemical markers, a clear and accurate definition is necessary. The diagnosis of CRPS is often by exclusion depending heavily on clinical examination, corroborated by bone scan. There are many published reports of cases of the RSD syndrome[36] in association with malignancy, including carcinoma of bowel, ovary, pancreas, lung, and chronic myelogenous leukaemia. In most of these CRPS was the presenting feature with the tumor being detected subsequently, with substantial time gap between the two.[7] This case highlights the association of CRPS with underlying malignancy. We did not find reports where the RSD syndrome reversed completely after successful tumor removal, therefore a direct cause-effect relationship is difficult to establish. Although, the etiology of CRPS is unknown, its occasional association with an apparently distant neoplastic process suggests that as yet unidentified circulating humoral factors may be responsible. It is possible that the tumor produces humoral factor(s) that may act at either the internuncial pool of the spinal cord to lower fiber threshold with increased activity spreading to sympathetic efferents or at a peripheral site to stimulate sympathetic fibers. There is an evidence to suggest that noradrenaline lowers the threshold of peripheral mechanoreceptors[8910] thus, enhancing abnormal firing in peripheral sensory nerves, which may account for the spontaneous pain and hyperaesthesia seen clinically. The case highlights the need for a thorough search for underlying malignancy in patients presenting with the so called ‘idiopathic’ CRPS.

This case also shows that CRPS can be associated with lung cancer and a keen observation on part of the imaging physician may help in its diagnosis and therapy. Spontaneous development of CRPS should alert the physician to the possibility of an underlying malignancy.