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Pancoast Syndrome
Introduction
Superior pulmonary sulcus tumors or Pancoast tumors arise from the apical pleuro-pulmonary groove superior to the first rib. When these tumors involve the surrounding structures such as the brachial plexus, cervical paravertebral sympathetic nervous system, and stellate ganglion, they cause a group of signs and symptoms collectively called Pancoast syndrome. This is characterized by the ipsilateral shoulder and arm pain, paresthesias, paresis, and atrophy of the thenar muscles of the hand, and Horners syndrome (ptosis, miosis, and anhidrosis). However, the Pancoast syndrome should be differentiated from the Pancoast tumor. The most common cause of the syndrome is primary bronchogenic carcinoma. The Pancoast syndrome is characterized by radiating parascapular pain, the hand's intrinsic muscles atrophy, and the presence of a density at the apex of the lung with localized destruction of ribs and vertebrae.[1][2][3][4]
Etiology
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Etiology
Tumors in the superior sulcus of the lung, typically non-small cell lung cancer, cause Pancoast syndrome. Among all lung cancers, non-small cell lung cancer (NSCLC) accounts for the majority with up to 80% to 85% of all cases, whereas Pancoast tumors by themselves account for roughly 3% to 5% of all lung cancers. More than 95% of Pancoast tumors are NSCLC, and among NSCLC, squamous cell carcinoma used to be the most common histologic type; however, lately, studies have been showing a predominance of adenocarcinoma.[5]
Other than bronchogenic carcinomas, malignancies such as primary adenoid cystic carcinomas, thyroid carcinomas, lymphomas, or metastasis from any primary carcinoma or even benign tumors occupying the superior pulmonary sulcus are known to cause Pancoast syndrome. Rarely, other malignancies, including paravertebral thoracic schwannoma and myxofibrosarcoma, may cause the clinical findings pertinent with the Pancoast syndrome.[6][7] Even apical lung infections or abscesses can cause Pancoast syndrome involving the chest wall and surrounding structures.[8][9][10]
Epidemiology
Lung cancer is the second most common cancer and is the main cause of oncological mortality in either gender, both in the United States and globally. There were more than 200,000 cases of lung cancer in 2017 and with a 5-year survival rate of 18%, more than 150,000 died from lung cancer in 2017. Among all lung cancers, non-small cell lung cancer accounts for the majority with up to 80% to 85% of all cases; whereas, Pancoast tumors by themselves account for roughly 3% to 5% of all lung cancers.[11]
Pathophysiology
Pancoast or superior sulcus tumors, when they compress or invade the surrounding structures, cause a group of symptoms collectively called Pancoast syndrome. They typically involve the brachial plexus first and cause shoulder and arm pain in almost all patients. They can also involve the parietal pleura, ribs, or vertebral bodies and cause pain. Since pulmonary symptoms occur late in these patients, initial symptoms are often misdiagnosed as musculoskeletal, and diagnosis is often delayed.[12]
When the tumor extends further, it can also cause C8 through T1 radiculopathy with pain and paresthesia of the medial half of the fourth finger, fifth finger, and medial side of the hand, forearm, and arm. The weakness of intrinsic hand muscles affects fine motor skills and handgrip.[13][14][15]
When the tumor involves the sympathetic trunk and the cervical ganglion, initially patients can develop ipsilateral facial flushing and sweat due to irritation. Later with invasion, Horner syndrome with ipsilateral ptosis, miosis, and anhidrosis can be seen along with sometimes contralateral flushing and sweating as well. This happens due to a hyperactive contralateral sympathetic reaction called Harlequin syndrome.[16][17]
Histopathology
Squamous cell carcinoma historically has been the most common subtype associated with Pancoast tumors. However, adenocarcinoma has been predominant in recent times. Overall, the overwhelming majority of Pancoast tumors are non-small cell lung cancer (NSCLC).[18]
History and Physical
Pancoast syndrome refers to the collective group of symptoms associated with these tumors, which is secondary to the involvement of brachial plexus and associated chest wall, vertebral, or rib pain. Shoulder or arm pain with associated paresthesias along the medial half of the fourth, fifth fingers and medial side of the hand, arm, and forearm due to C8 through T1 radiculopathy are usually primary symptoms associated. Since they are apically located, pulmonary symptoms of shortness of breath do not develop until later, as the tumor begins to involve more of the lung.[19][14][20]
Physical examination findings include ipsilateral facial flushing and sweating due to the involvement of the sympathetic trunk and cervical ganglion. Horner syndrome with ptosis, miosis and anhidrosis may also develop with the further extent of the tumor.[8]
Evaluation
There are no laboratory abnormalities specific to the Pancoast tumor.
A chest x-ray can be used for initial screening, which shows the increased size of the apical cap or apical mass of the lung. CT scan provides additional information with regards to the extent of the tumor, satellite nodules, as well as mediastinal adenopathy, all of which are vital in the staging of these tumors. Although CT has poor sensitivity and specificity for accurate local staging, especially in evaluating the brachial plexus, subclavian vessel, and chest wall involvement, it identifies bony involvement.[9][21]
MRI of the neck, chest and upper abdomen usually is done after the diagnosis is made and before surgery to identify the extent of vascular and brachial plexus involvement. However, MRI has been suggested as more useful in these tumors, as it helps better delineate soft tissue involvement, invasion of brachial plexus, vasculature, and spinal involvement. Therefore, MRI is currently preferred on potentially surgically resectable tumors.[6]
Due to the outer location of these tumors, CT-guided core biopsy is the diagnostic test of choice with a reported yield of more than 90%. Bronchoscopy has been reported to be diagnostic in around 30% to 40% of the cases, which maybe because of the presence of an additional endobronchial tumor. Sputum cytology and scalene node biopsies usually have a low yield.[22][23]
Treatment / Management
The Standard of care is currently chemoradiation therapy followed by surgical resection.[1][23][24][25][26](A1)
Induction chemoradiation therapy involves chemotherapeutic regimens, including Cisplatin/Etoposide or Cisplatin/Mitomycin C/Vindesine. Radiation therapy regimes usually include 45 Gy/27 fractions over 5 to 6 weeks, followed by surgery in 4 to 6 weeks after completion of chemoradiation therapy.[27][28](B2)
Contraindications to surgical resection include:
Differential Diagnosis
Other malignancies either primary adenoid cystic carcinomas, hemangiopericytomas, thyroid carcinomas, lymphomas, plasmacytomas, or metastasis from any primary carcinoma, or even benign tumors occupying the superior pulmonary sulcus are known to cause Pancoast syndrome.[31]
Even apical lung infections or abscesses can also cause Pancoast syndrome if they involve the chest wall and surrounding structures.[32]
Surgical Oncology
Resectable NSCLC superior sulcus tumors (T3 invasion, N0-1) are best treated with trimodality therapy comprising systemic chemotherapy, radiation treatments, and surgical resection. NCCN panel advocates for neoadjuvant concomitant chemotherapy and radiation treatments accompanied by surgical resection and chemotherapy again. This practice of neoadjuvant chemoradiation before surgery has shown a 2-year survival of approximately 50 to 70% and a 5-year survival rate of roughly 40%.[33]
For T3–4, N0–1 lesions involving chest wall, proximal airway, or mediastinum, surgery is done first followed by chemotherapy alone if surgical margins are negative. If surgical margins are positive, they receive concurrent chemoradiation followed by re-resection and chemotherapy.[34][11]
Medical Oncology
In patients with unresectable NSCLC superior sulcus tumors (T4 extension, N0–1) full dose systemic chemotherapy is given concurrently with radiation treatments. These tumors can be reassessed with CT or FDG-PET/CT scans after treatments for resectability. If the lesion remains unresectable, these patients may benefit from consolidation therapy with durvalumab which is an anti-PD-L1 monoclonal antibody (Programmed Death Ligand 1) after completion of chemoradiation.
Staging
Roughly three-quarters of Pancoast tumors are stage III tumors as they involve the parietal pleura, and the rest are regularly stage IIB and stage IV with the involvement of brachial plexus, mediastinum, great vessels, vertebral body, or with distant metastases.
According to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Eighth Edition, stage IIB now includes any tumor regardless of its size with metastasis or direct invasion of ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, i.e., all N1 tumors. Stage IIB also includes T3 tumors which are greater than 5 cm but less than or equal to 7 cm in greatest dimension or directly invading parietal pleura, chest wall, phrenic nerve, parietal pericardium, or with 1 or more separate tumor nodules in the same lobe as the primary.
Stage III includes any tumor regardless of its size with N2 or N3 regional node involvement. These are tumors with metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes (N2) and metastasis to contralateral mediastinal and/or hilar lymph nodes as well as scalene and/or supraclavicular lymph nodes regardless of laterality (N3). Stage III also includes T3 tumors with N1 lymph node involvement and any T4 tumor. T4 tumors are greater than 7 cm or invading the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina or with 1 or more tumor nodules in an ipsilateral lobe that is different from that of the primary.[27]
Prognosis
As with most other malignancies, patients with early-stage disease at diagnosis and better performance status have a good prognosis; whereas, advanced disease, poor performance status, and weight loss are indicators of poor outcomes. Also, metastatic NSCLC patients eligible for treatment with targeted therapies have a better prognosis compared with those without targetable genomic variations.
It is very important to promptly identify the symptoms and diagnose Pancoast syndrome as they are usually stage IIB or higher by the time they are diagnosed. Early detection, staging, and treatment are therefore critical for long-term survival.[35]
Complications
The complications are chiefly related to the treatments:
- Surgery: Atelectasis, pain, chest wall deformity, frozen shoulder, CSF leak, prolonged air leak, injury to the brachial plexus
- Chemotherapy: Side effects from the drugs
- Radiation: alopecia, nausea, vomiting, leathery skin, poor wound healing
Consultations
- Pulmonologist
- Thoracic surgeon
- Pain specialist
- Critical care specialist
Pearls and Other Issues
- NSCLC is the most common cancer associated with Pancoast tumor.
- Pancoast syndrome refers to superior sulcus tumors along with ipsilateral shoulder and arm pain, paresthesias, paresis and atrophy of the thenar muscles of the hand and Horners syndrome (ptosis, miosis, and anhidrosis).
- Trans-thoracic needle biopsy usually achieves a diagnosis.
- Preoperative evaluation will need MRI to delineate vascular involvement.
- Treatment involves chemoradiation therapy followed by surgical resection.
Enhancing Healthcare Team Outcomes
Pancoast tumor has no cure, and the survival is abysmal. The cancer is often diagnosed late, and patients are subject to complex surgery which is not only painful but rarely results in a cure. Thus, the emphasis today is on prevention. One of the most common causes of lung cancer is smoking and nurses and pharmacists are in a prime position to educate the patients about the adverse effects of tobacco. Plus the nurse can educate the patient on the type of surgery, the potential side effects of radiation therapy, and chemotherapy. The pharmacist can also recommend aids to stop smoking. Further, the pharmacist can educate the patient on work hazards that have been linked to lung cancer. Finally, the patient must be educated on a healthy lifestyle, exercise and abstaining from alcohol. This advice has benefits beyond lung cancer- it can improve the quality of life and lower the cost of healthcare.[36][24] (Level V)
Outcomes
The prognosis for most patients with Pancoast cancer is poor. Less than 30% are alive at five years. To date, radiation therapy has made no difference in locoregional recurrence or long-term survival. For those who undergo surgery, the quality of life is very poor, and the pain from the surgery can be debilitating.[37][36] (Level III)
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