Practice Essentials
Pancoast syndrome (Pancoast’s syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3, 4] This produces the following clinical manifestations:
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Severe pain in the shoulder region radiating toward the axilla and scapula, with later extension along the ulnar aspect of the arm to the hand
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Atrophy of hand and arm muscles
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Compression of the blood vessels with edema
Most Pancoast tumors are non–small cell lung cancer (NSCLC])—specifically, squamous cell carcinoma (SCC) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Very rarely, tumors in this location may have metastasized from other sites. [5, 6]
Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [7] Careful assessment and appropriate staging are performed before surgery, and selected patients are administered preoperative irradiation of 30 Gy over 2 weeks. After an interval of 2-4 weeks, surgical resection of the chest wall and lower brachial plexus and en bloc lung resection produces a 5-year survival rate of 30%. Contraindications to surgical management include the following:
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Extension of the tumor into the neck or vertebrae
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Presence of substantial mediastinal lymph nodes
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Peripheral tumor dissemination
Protocols that use combinations of radiation therapy, chemotherapy, and surgery are currently being studied to determine the best therapy.
Pathophysiology
Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical pattern. [8]
The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:
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Intercostal nerves
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Lower roots of the brachial plexus
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Stellate ganglion
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Sympathetic chain
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Adjacent ribs and vertebrae.
Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, thus causing pain in the shoulder and along the ulnar nerve distribution of the arm and hand. [9] (These carcinomas also cause Horner syndrome.) These apical lung tumors tend to be locally invasive early. In the absence of metastases and regional nodal involvement, these apical cancers can be successfully treated.
The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs. [10]
The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.
Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.
Etiology
The overwhelming majority of cases of Pancoast syndrome are non–small cell lung carcinoma (NSCLC), with more than 95% located in the superior sulcus. The most common varieties are SCC and adenocarcinoma; large cell carcinoma has also been reported.
Although quite rare (responsible for fewer than 5% percent of cases in most series), small cell carcinoma is also observed. Maggi et al reported small cell carcinoma in only 3 of the 60 patients in their series. [10] More typically, small cell carcinoma manifests in a central rather than a peripheral location.
Although NSCLC is by far the most common cause of Pancoast syndrome, the list of differential diagnoses is broad. Because of the wide variety of diseases that can produce Pancoast syndrome, a histologic diagnosis is mandatory before definitive treatment is initiated.
Rare causes include the following:
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Desmoid tumors [11]
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Hemangiopericytoma [12]
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Adenoid cystic carcinoma [13]
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Lymphoma [14]
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Thyroid carcinoma [15]
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Vascular aneurysms
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Amyloid nodules
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Cervical rib syndrome
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Inflammatory pseudotumor (plasma cell granuloma)
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Mycotic subclavian artery aneurysm
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Carotid pseudoaneurysm in a child (caused by a hydatid cyst)
Risk factors are similar for almost all lung cancers and include the following:
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Tobacco smoking
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Secondary smoke exposure
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Prolonged asbestos exposure
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Exposure to industrial elements (eg, gold, nickel)
Epidemiology
Overall, Pancoast tumors are much less common than other lung cancers, accounting for fewer than 5% of these cancers (1-3% in various previous series). [20, 21] Originally deemed universally fatal, Pancoast tumors are now amenable to curative treatment because of improvements in combined modality therapy and development of new techniques for resection.
Prognosis
The prognosis for patients with Pancoast syndrome is stage dependent. Adverse prognostic factors include the following:
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Presence of Horner syndrome
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Involvement of mediastinal lymph nodes
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Incomplete resection
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Involvement of supraclavicular lymph node
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Vertebral body invasion
To date, no patient with the first 3 prognostic factors has survived for 5 years.
Distant disease limits survival. Treatment failure is especially frequent in patients with involvement of the brain. The authors recommend careful surveillance for brain metastasis during and after the therapy. The authors also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.
Mortality and survival
Attar et al reported a median survival of 36.8 months in patients with T3 lesions undergoing combined modality treatment; median survival was only 6.4 months if the patient had T4 disease. [22]
Overall survival data were summarized by Detterbeck, who noted that 5-year survival rates ranged from 15% to 56%. [23] Of the 104 patients treated by Attar and coworkers, 7 (~7%) were 5-year survivors and 3 (~3%) were 10-year survivors. [22] Another study demonstrated surgical morbidity rates of 7-38%, with mortality ranging from 5% to 10%. [24]
For neoplastic causes, predictors of 5-year survival are weight loss, supraclavicular fossa or vertebral body involvement, disease stage, and surgical treatment. A study by an MD Anderson group reported the following findings [25] :
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For patients with stage IIB disease, the 5-year survival rate was 47%, whereas for those with stage IIIA and IIIB disease, it was 14% and 16%, respectively
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In patients with stage IIB disease, surgical treatment and weight loss were significant independent predictors of 5-year survival
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Among patients with stage IIIA disease, the only predictor of survival was the Karnofsky performance score
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In patients with stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than a left superior sulcus location
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Compared with patients who had squamous cell tumors, more patients with adenocarcinoma had cerebral metastases within 5 years
Relapse
Locoregional relapse is common despite preoperative or postoperative radiation therapy. Muscolino et al found locoregional recurrence in 60% of patients treated with a combined radiosurgical approach. Ginsberg et al found that 94 of their 124 patients had recurrence of disease, with 72% of these cases being locoregional at initial recurrence. In two thirds of patients who underwent complete resection, local recurrences were the first site of relapse. [20]
This distribution of relapses was noted in several studies reviewed by Detterbeck. In many of these studies, patients received preoperative radiation therapy. [23] In the Memorial Sloan-Kettering experience, additional postoperative brachytherapy was administered to achieve maximal possible local control; despite these measures, local relapses and, ultimately, distant relapses were frequent. [20]
Tables
Stage |
T(Tumor) |
N (Nodes) |
IIB |
T3 |
N0 |
IIIA |
T3 |
N1 |
IIIB |
T3 |
N2 |
IIIC |
T3, T4 |
N3 |
