Pancoast’s syndrome caused by lymph node metastasis from breast cancer

Abstract

Pancoast’s syndrome may be the result of neoplastic, inflammatory or infectious disease. We report an unusual case of Pancoast’s syndrome in a patient with metastatic breast cancer. A 54-year-old woman, affected by metastatic breast cancer, presented for severe shoulder pain, paraesthesia and numbness in the right arm. Despite further multiple lines of systemic chemotherapy, she developed a progressive enlargement of retropectoral, supraclavicular and infraclavicular lymph node metastases, which involved brachial plexus, apex of lung and anterior mediastinum. Physical examination revealed severe weakness of proximal muscles of the right arm. Neuropathic pain was managed with pharmacological treatment. Lastly, the patient has been treated with intrathecal analgesia with morphine and ziconotide with a good control of pain. The patient died after 3 months.

Background

Pancoast’s syndrome (PS) consists of a constellation of signs and symptoms including severe shoulder pain, due to invasion of the chest wall and brachial plexus, Claude-Bernard-Horner syndrome, related to invasion of the sympathetic chain and inferior cervical ganglion, weakness of muscles innervated from C8-T1, due to infiltration of the ulnar nerve and, sometimes, upper arm oedema, in case of occlusion of the subclavian vein.

PS may be the result of neoplastic, inflammatory or infectious disease. Apical lung tumour is the most known cause of PS. However, breast cancer (BC) can also damage structures of the thoracic inlet by direct invasion of the tumour, by spread of metastatic lymph nodes or by pleural metastases. The relationship between PS and BC is intricate and radiation-induced brachial plexopathy should also be considered in the differential diagnosis of a patient with a known history of BC.¹

Furthermore, pain from neoplastic brachial plexopathy often proves difficult to manage and may become disabling.

Case presentation

A 54-year-old woman presented for persistent and severe right shoulder pain, paraesthesia and numbness in the right arm.

She had received a diagnosis of right inflammatory BC with multiple bone metastases 12 years before. After first-line chemotherapy, she underwent right radical mastectomy and axillary dissection with histological evidence of residual disease from surgical breast and lymph nodes specimens. Subsequently, three different lines of endocrine therapies were administered achieving a prolonged disease control.

Of note, 7 years later, the patient presented with palpable nodal metastases in the supraclavicular and infraclavicular region, confirmed through biopsy. The disease showed a good clinical response to external radiotherapy and to two different regimens of systemic chemotherapy.

However, 3 years later, the patient had severe right shoulder pain with worsening of right arm oedema.

Despite further multiple lines of systemic chemotherapy, she developed a progressive enlargement of retropectoral, supraclavicular and infraclavicular lymph node metastases with stable disease in the other sites of metastasis.

Neurological examination demonstrated hypotrophy and severe weakness of deltoid, biceps and triceps brachii (Medical Research Council, 0/5). Cranial nerves were normal, except for slight anisocoria with right miosis. Sensation and strength were normal in the other limbs.

Investigations

MRI showed an solid mass of 9 cm in the supraclavicular and subclavicular region, enhanced in T1 postcontrastographic sequences, with invasion of brachial plexus, pectoral muscle, common carotid artery, subclavian artery, anterior mediastinum and lung apex compression (figure 1).

Figure 1.

MRI findings showing extensive involvement of right brachial plexus. In (A) coronal and (B) axial T1-weightened sequences showing an infiltrating mass encasing the right brachial plexus.

Nerve conduction studies were not performed due to poor patient compliance and considerable pain.

Treatment

The pain team was early involved in the management of our patient care. Palliative care focused on providing relief from neuropathic pain.

At the beginning, she was administered acetaminophen and oral weak opioid analgesics. When neoplastic brachial plexopathy worsened, the pain team suggested first pregabalin and corticosteroids, then transdermal buprenorphine and indomethacin with no enough relieve on symptoms. Finally, 3 months before death, after failure with medical therapy, the pain team proposed the placement of intrathecal catheter with infusion of morphine and ziconotide, achieving a good clinical response.

Outcome and follow-up

A few days after the analgesic procedure, the patient experienced orthostatic headache and vomit, suggesting an intracranial hypotension as a complication of intrathecal catheter positioning. It was confirmed by CT of the brain, which showed a subdural effusion.

In order to prevent further pericatheter cerebrospinal fluid leakage, the patient was treated with an epidural blood patch. After a period of approximately 3 months, the patient died.

Discussion

In the present case, we described clinical and radiological feature of PS^{2 3} due to progressive enlargement of supraclavicular and retropectoral lymph node metastasis from BC that involved brachial plexus, apex of lung and anterior mediastinum in a 54-year-old woman.

The majority of neoplastic cases of PS are caused by non-small-cell lung cancer,¹ followed by other primary or metastatic thoracic neoplasms. The incidence of ipsilateral supraclavicular lymph node metastasis in BC is reported to be as low as 1%–4.3%.⁴

Even if brachial plexopathy from BC has been previously reported in literature,^{1 5 6} to our knowledge, there are no studies describing ‘PS’ due to BC.

In a review on neuroimaging,⁵ MRI is the modality of choice for evaluation of brachial plexus and its pathological involvement. Among 104 cases with non-traumatic brachial plexopathy, radiation fibrosis (31% of cases), metastatic BC (24%) and primary or metastatic lung cancer (19%) were the most common causes. Metastatic lesions typically appear with low signal on T1-weighted sequences and increased on T2-weighted sequences. Lesions originating in the lung parenchyma usually have an irregular interface with the pulmonary parenchyma, whereas pleural and extrapleural lesions tend to have smooth borders.^{5 7}

Nevertheless, it remains difficult to differentiate between malignancy and radiation plexopathy on the basis of imaging, because both can show enhancement after gadolinium administration. In order to achieve the correct diagnosis the clinical picture, including the history, electromyographical findings play an important role. In this setting of patients, the positron emission tomography should be further evaluated.⁶

According to the literature,⁸ shoulder pain preceded the development of other neurological symptoms and signs. In this case, a prominent arm lymphoedema was related also to axillary dissection and it worsened with the onset of shoulder pain.

Our patient presented normal cranial nerves, except for slight anisocoria with right miosis, which is concordant with a Horner’s syndrome. However, in absence of ptosis and loss of hemifacial sweating, we could not achieve a defined diagnosis and MRI did not demonstrate sympathetic nerve involvement.

The treatment of patients with brachial plexopathy from pathological lymph nodes and recurrent BC may include lymph node dissection. In palliation, chemotherapy plus irradiation seems to obtain median time to progression rates superior to those reported for radiotherapy alone.^{4 9 10}

Progressive and severe pain represents the predominant complaint in PS.⁶ In these patients, pain from neoplastic brachial plexopathy can be caused by involvement of the brachial plexus, parietal pleura, endothoracic fascia, vertebral bodies and ribs. In fact, pain is often really difficult to manage and may become disabling as disease progresses.^{11 12} However, there is lack of reports concerning efficacy of therapies and management of pain in these patients.¹³

If oral therapy fails or intolerable side effects to systemic opioids develop, intrathecal analgesia has been proposed as a therapeutic option.¹⁴ Although there are potential benefits, this technique has dangerous complications due to catheter insertion, including cerebrospinal fluid leakage, which is usually managed with an epidural blood patch.¹⁵ It has been described treatment of neuropathic pain by local anaesthetics administered through an axillary catheter placed in the brachial plexus.¹⁶ Among invasive approaches, Gofeld and Bhatia proposed the use of real-time ultrasound guidance to facilitate percutaneous ablation of cervical nerve roots in a patient with PS with complete pain relief at 3-month follow-up.¹⁷

In conclusion, PS has a poor prognosis and is difficult to manage. This condition is often accompanied by a late diagnosis and can benefit from several conservative and invasive treatments. For these reasons, we suggest that pain due to injury to the brachial plexus should be treated under the supervision of a multidisciplinary pain team.

Learning points.

• Breast cancer metastases could compress or infiltrate structures of the thoracic inlet causing Pancoast’s syndrome.

• MRI of the brachial plexus is the gold standard in the evaluation of brachial plexopathy and could differentiate among malignancy, radiation plexopathy and fibrosis.

• Progressive and severe neuropathic pain represents the predominant complaint in Pancoast’s syndrome: a simultaneous care with implication of different specialists has a key role in the management of these patients.