AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Pancoast syndrome is characterized by a malignant neoplasm of the superior sulcus of the lung with destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). This is accompanied by (1) severe pain in the shoulder region radiating toward the axilla and scapula along the ulnar aspect of the muscles of the hand, (2) atrophy of hand and arm muscles, (3) Horner syndrome (ptosis, miosis, hemianhidrosis, enophthalmos), and (4) compression of the blood vessels with edema.

In 1924, Pancoast published his first paper describing tumors of the pulmonary apex. In a 1932 report, he described in greater detail the syndrome that now bears his name. Medical historians note that Hare published a report in 1838 that may have included the first description of tumors of the superior sulcus.

Pathophysiology

The overwhelming majority of cases of Pancoast syndrome are non–small cell lung carcinoma, with more than 95% located in the superior sulcus. The most common varieties are squamous cell carcinoma or adenocarcinoma. Small cell carcinoma is observed in fewer than 5% percent of cases in most series.

Other causes include nonepithelial neoplasms (eg, lymphoid malignancies, metastatic cancers of nonpulmonary causes), infections, lymphomatoid granulomatosis, vascular aneurysms, amyloid nodules, and cervical rib syndrome. Inflammatory pseudotumor (plasma cell granuloma), mycotic subclavian artery aneurysm, and carotid pseudoaneurysm in a child (caused by a hydatid cyst) have been reported. Because of the wide variety of diseases that can produce Pancoast syndrome, a histologic diagnosis is mandatory before initiating definitive treatment.

Frequency

United States

Pancoast tumors are uncommon and comprise fewer than 5% of all lung cancers (Ginsberg, 1994; Johnson, 1997).

Mortality/Morbidity

For neoplastic causes, predictors of 5-year survival are weight loss, supraclavicular fossa or vertebral body involvement, disease stage, and surgical treatment. A recent study by an MD Anderson group reported the following findings:

• For patients with stage IIB disease, the 5-year survival rate was 47%, while those with stage IIIA or IIIB disease had survival rates of 14% and 16%, respectively.
• In patients with stage IIB disease, surgical treatment and weight loss were significant independent predictors of 5-year survival.
• Among patients with stage IIIA disease, the only predictor of survival was the Karnofsky performance score.
• 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 that of patients with tumors in the left superior sulcus.
• Compared with patients who had squamous cell tumors, more patients with adenocarcinoma had cerebral metastases within 5 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients may present with referred pain over the scapula to the shoulder as the result of damage to the afferent pain fibers of the sympathetic trunk. Pain in an ulnar nerve distribution along the medial aspect of the arm to the fingers results from involvement of the lower brachial plexus, the eighth cervical nerve, and the first thoracic nerve. This may be associated with hand weakness.

Many patients are initially treated for presumed local musculoskeletal conditions such as bursitis and vertebral osteoarthritis with radicular pain. Symptoms may persist for many months before evaluation for progression reveals the cause. In a 1994 series by Maggi and colleagues, symptoms lasted 2-36 months, with a mean of 9.7 months. According to case records of the Massachusetts General Hospital: weekly clinicopathological exercises from 2000, the interval from onset of symptoms to diagnosis was 3.5 years. In 1997, Muscolino described plexopathy or radicular symptoms in 53% of 15 patients.

Physical

Physical examination may reveal findings consistent with Horner syndrome, such as ptosis and miosis, which result from paralysis of the dilating sympathetic fibers. Supraclavicular lymphadenopathy may also be observed.

Horner syndrome is the result of invasion of the lower cervical and first thoracic ganglia, which frequently fuse into a single ganglion, the stellate ganglion. Horner syndrome is observed in 20-50% of patients at presentation (Ginsberg, 1994; Maggi, 1994; Muscolino, 1997; Attar, 1998). Decreased sweating on the affected side and ptosis of the denervated lid may be observed. Application of topical cocaine to the miotic eye (contracted pupil) fails to cause pupil dilation, while appropriate dilation is noted in the unaffected eye (Balcer, 1997).

The tumor may invade the bony structures of the chest. The first or second thoracic vertebra or the first, second, or third ribs may be invaded. In a review of 60 patients with Pancoast tumors, Maggi and associates 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 three ribs. 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.

Cough, dyspnea, and hemoptysis, which are signs often associated with lung cancer, are not as common in individuals with Pancoast syndrome because of the peripheral location of the tumor. When present, they are associated with a worse prognosis. Also uncommon but occasionally noted are more advanced tumors with involvement of the recurrent laryngeal nerve, phrenic nerve, or superior vena cava.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Non–small cell lung cancer is the most common etiology; adenocarcinoma, squamous cell carcinoma, and large cell carcinoma have all been observed. Overall, Pancoast tumors are uncommon and comprise fewer than 5% of all lung cancers (Ginsberg, 1994; Johnson, 1997). While non–small cell lung cancer is the most common cause of Pancoast syndrome, the differential diagnosis is broad. Although quite rare, small cell lung cancer is also observed. Maggi and colleagues reported only 3 patients with small cell carcinoma in their 1994 series of 60 patients. More typically, small cell carcinoma manifests in a central location rather than a peripheral.

A diverse variety of unusual causes may be involved. Rarely, benign tumors such as desmoid tumors (case records of the Massachusetts General Hospital: weekly clinicopathological exercises, 2000) or hemangiopericytoma (Chong, 1993) may cause the condition. Adenoid cystic carcinoma (Hatton, 1993), metastatic carcinoma (Amin, 1986), lymphoma (Mills, 1994), and thyroid carcinoma (Rabano, 1991) have all been associated with the syndrome. Infectious processes, including bacterial (Vandenplas, 1991; Gallagher, 1992) and fungal infections (Simpson, 1986; Mitchell, 1992) may also be involved.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Imaging Studies

• Imaging and biopsy are the cornerstones of evaluation.
• The apex of the lung can be difficult to investigate because it is bounded laterally by the first rib, posteriorly by the first rib and the vertebral bodies, and anteriorly by the costal cartilage of the first rib and the manubrium. Plain radiographs of the chest frequently show no change or an asymmetry or thickening of the apical cap. Apical lordotic films may be more revealing. CT scans and MRIs have become standard imaging techniques.
• CT scans are less expensive than MRIs and much more available. CT scans can help assess bone destruction, and they are useful in the general imaging of the lung for the evaluation of mediastinal adenopathy, other pulmonary nodules, and liver involvement. MRIs may be more accurate in evaluating chest wall invasion, examining vascular structures, and assessing the brachial plexus for invasion (Heelan, 1989; Beale, 1992; Patz, 1999).
• Additional staging studies should be considered. Mediastinoscopy should be performed to evaluate mediastinal nodes. The presence of N2 mediastinal lymphadenopathy has a significant adverse effect on survival. A CT scan or MRI of the head to exclude occult metastasis should be performed if treatment with curative intent is planned. A CT scan of the chest can be extended to include the liver and adrenal glands.
• Since positron-emission tomography (PET) scanning is US Food and Drug Administration–approved for staging of non–small cell lung cancer in general, it is also being used in the setting of Pancoast syndrome.

Procedures

• Tissue diagnosis should be performed. However, if a patient presents with supraclavicular lymph node enlargement, then a fine-needle aspiration biopsy of enlarged supraclavicular lymph nodes or an ipsilateral supraclavicular fullness procedure is a fast, safe, and inexpensive means of confirming the diagnosis.
• Sputum cytology results are positive in fewer than 15% of patients (Anderson, 1986). Fiberoptic bronchoscopy findings are more often positive, but only in 20-30% of patients, because of the peripheral location of the tumor (Maxfield, 1987). Bronchoscopy, however, can be useful in excluding otherwise unsuspected concurrent endobronchial lesions.
• Transthoracic needle biopsy by CT guidance has a high yield, up to 95% in some series (Paulson, 1985; Anderson, 1986; Shaham, 2000). Some tumors may be evaluated only by thoracotomy, either open or video assisted.

Staging

The American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC) have adopted the International System for Staging Lung Cancer (Mountain, 1997). This classification stages lung cancers by describing tumor characteristics and tumor distribution.

The T designation describes the size and invasiveness of the primary tumor. T3 indicates a tumor of any size that invades the chest wall (the parietal pleura). T4 is a tumor of any size that invades the vertebral body, neural or vascular structure, mediastinum, esophagus, or trachea.

The N designation describes the distribution of positive lymph nodes. N1 indicates metastasis to ipsilateral peribronchial or hilar nodes. N2 indicates the spread to ipsilateral mediastinal and/or subcarinal nodes. N3 indicates metastasis to nodes of the contralateral hilar and mediastinal areas or scalene or supraclavicular nodes, either ipsilateral or contralateral.

The M designation describes the extent of distant metastasis. M0 indicates no identifiable metastatic disease, and M1 designates the presence of distant metastasis (eg, brain, bone, liver). Any M1 findings indicate stage IV disease.

AJCC Stages for Pancoast Tumors

Stage	T (tumor)	N (nodes)
IIB	T3	N0
IIIA	T3	N1
	T3	N2
IIIB	Any T	N3
	T4	Any N

Attar and coworkers reviewed their experience with 105 patients treated during 1955-1997. They found that 30% of patients presented with T3 N0 disease (stage IIB), 26% with T4 N0 (stage IIIA), and 25% with metastatic disease (M1, stage IV). In their review of 124 patients, Ginsberg and colleagues found that 58% of patients had T3 N0 disease, 16% had T3 N2, and only 1% had T3 N1. In addition, 6% of patients had T3 N3 disease, 18% had T4 N0, and 1% had T4 N.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Today, in accordance with Rusch and colleagues' 2001 trial findings, most centers use cisplatin-based chemotherapy with etoposide and concurrent radiotherapy as neoadjuvant treatment, followed by surgical resection, as the standard of care for this group of patients. One cautionary note is that this trial mandated a negative mediastinoscopy result. The preoperative radiotherapy dose was 4500 cGy in 25 fractions.

Surgical Care

• Historically, these tumors have been difficult to treat. In the 1950s, they were considered inoperable.
• • In 1956, Chardack and MacCallum reported the first 5-year survival of a patient treated with resection and postoperative radiation therapy.
  • The combination of radiation and surgery was further evaluated, and in 1961, Shaw and Paulson published a report of 18 patients treated with preoperative radiation therapy and surgical resection. They found a significant increase in resectability and cure; thereafter, preoperative radiation followed by surgery became the standard of care.
• In many centers, the current practice is to individualize a treatment plan for each patient. Frequently, treatment decisions are made by a multidisciplinary thoracic oncology group with attention to adverse prognostic factors.
• • The surgical treatment of choice is complete removal of the tumor by en bloc chest wall resection combined with lobectomy and node staging (Ginsberg, 1994). Depending upon the extent of local invasion, surgical treatment may require resection of the paravertebral sympathetic chain, stellate ganglion, lower trunks of the brachial plexus, subclavian artery, or portions of the thoracic vertebrae.
  • Radiation and chemotherapy may benefit local and systemic control by addressing individual adverse findings.
  • In many centers, neoadjuvant or induction chemoradiotherapy is administered to patients with potentially resectable tumors. Important factors include T category, nodal status, presence of Horner syndrome, and completeness of resection (Ginsberg, 1994; Arcasoy, 1997; Detterbeck, 1997; Johnson, 1997; Muscolino, 1997; Attar, 1998). Surgery is generally undertaken 2-4 weeks after the completion of radiation therapy.
  • For tumors that invade the brachial plexus, the spine, or both, a combined thoracic-neurosurgical approach is warranted.
• A lung intergroup trial (SWOG 0220) is studying induction therapy with cisplatin, etoposide, and radiotherapy with 45 Gy, followed by resection if possible, and postoperative docetaxel.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.

Drug Category: Antineoplastic agents

These agents inhibit cell growth and proliferation. Treat head, neck, breast, testicular, and ovarian cancer; Hodgkin and non-Hodgkin lymphoma; neuroblastoma; sarcomas; bladder, gastric, lung, esophageal, cervical, and prostate cancer; myeloma; melanoma; mesothelioma; SCLC; osteosarcoma; ANLL; hepatoma; rhabdomyosarcoma, mycosis fungoides, uterine carcinoma, histiocytosis; gestational trophoblastic disease; Ewing sarcoma, Kaposi sarcoma, Wilms tumor, and brain tumors.

Drug Name	Etoposide (Toposar, VePesid)
Description	A semisynthetic derivative of podophyllotoxin with antineoplastic properties; it interferes with the function of topoisomerase II, thus inhibiting DNA synthesis, and is most active against cells in the late S and G(2) phases of the cell cycle.
Adult Dose	PE regimen: 100 mg/m2 IV on days 1-3 of cycle; repeat q3-4wk for 4-6 cycles; administer by slow IV infusion, over at least 30 min, as a solution in isotonic sodium chloride solution (0.9%) or glucose (5%) injection Single-agent regimen: 50 mg PO bid for days 1-14 of cycles; repeat cycle q3-4wk for 4-6 cycles; adjust dose in hepatic or renal dysfunction Total bilirubin (TB) = 1.5-3 mg/dL: 50% dose reduction TB = 3.1-4.9 mg/dL: 75% dose reduction TB > 5 mg/dL: Avoid use CrCl = 15-50 mL/min: 25% dose reduction
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; IT administration (may cause death)
Interactions	May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine has additive effects in cytotoxicity of tumor cells; high dose of cyclosporine (serum concentration >2000 ng/mL) decreases clearance, leading to increased risk of neutropenia; zidovudine increases serum concentration, resulting in increased toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	Bleeding, severe myelosuppression, nausea, vomiting, hypotension, allergic reaction, and alopecia may occur; reduce dose in hepatic (eg, increased TB) or renal (eg, decreased CrCl) impairment

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prognosis

• Prognosis is stage dependent.
• • Attar and coworkers 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.
  • Vertebral body invasion is generally associated with a poor prognosis.
  • Newer surgical approaches may prove beneficial. In 1993, Dartevelle and colleagues presented their experience with an anterior transcervical thoracic approach that permitted greater exposure and control of the vascular structures of the thoracic inlet, which facilitated resection in situations in which vascular structures were invaded.
  • The presence of Horner syndrome and nodal involvement are associated with an inferior prognosis.
  • Overall survival data were summarized by Detterbeck, who noted that 5-year survival rates ranged from 15-56%. Of the 104 patients treated by Attar and coworkers, 7 (~7%) were 5-year survivors and 3 (~3%) were 10-year survivors. Another study demonstrated surgical morbidity rates of 7-38%, with mortality ranging from 5-10% (Arcasoy, 1997).
• Analysis of patterns of failure may help suggest alternate treatment strategies.
• • Locoregional relapse is common despite preoperative or postoperative radiation therapy. Muscolino and coworkers found locoregional recurrence in 60% of patients treated with a combined radiosurgical approach. Ginsberg and associates 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.
  • This distribution of relapses was noted in several studies reviewed by Detterbeck. In many of these studies, patients received preoperative radiation therapy. 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 (Ginsberg, 1994).
• Distant disease limits survival. Brain metastasis is the most frequently reported site of distant disease, and bone metastasis is almost as common (Ginsberg, 1994; Maggi, 1994).

Patient Education

• For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Hand, Wrist, Elbow, and Shoulder Center. Also, see eMedicine's patient education articles Lung Cancer and Shoulder and Neck Pain.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to make the diagnosis of a Pancoast tumor is a potential source of medicolegal liability. Primary care physicians, rheumatologists, orthopedic surgeons, and neurosurgeons must be aware of this possibility, particularly in patients who smoke.

Special Concerns

• Future directions
• • While preoperative radiation followed by complete en bloc resection is an advance over previous treatment paradigms, the high frequency of local recurrence despite aggressive measures coupled with the eventual development of distant disease and death prompt continued exploration of novel approaches.
  • The introduction of chemotherapy into the treatment plan and newer modes of radiation therapy bring the possibility of additional progress. Since Pancoast tumors are an uncommon subset of lung cancer, the number of cases has been insufficient to justify conclusions; however, new approaches to the general treatment of patients with regionally advanced disease (T3, chest wall invasion) are undergoing evaluation with chemotherapy, both with and without radiation therapy.
  • Since a major concern for overall survival is systemic control, the patient is given immediate therapy that may reduce micrometastatic disease.
  • Several early trials demonstrated survival benefits in small groups of patients (not Pancoast patients) with locally advanced lung cancer treated with preoperative chemotherapy (Rosell, 1994; Roth, 1994). The largest study of this kind, reported by Albain and coworkers, reported complete pathologic responses in 21% of surgical patients following preoperative concurrent chemotherapy and radiation therapy. The optimal chemotherapeutic regimen has not yet been identified, and newer agents may improve responses (Langer, 1999).
• Summary
• • Pancoast syndrome induces pain in the shoulder, scapula, or arm and is sometimes associated with Horner syndrome. Pancoast syndrome results from a tumor of the pulmonary apex, most often a non–small cell lung cancer.
  • Preoperative radiation therapy has improved resectability rates, and the addition of preoperative chemotherapy, with radiation therapy, holds the possibility of additional improvements in resectability and ultimate cure. Adverse prognostic findings include Horner syndrome, invasion of major vascular structures or vertebral bodies, N2 or N3 disease, and incomplete resection.
  • Patients with superior sulcus tumors should be encouraged to enroll in prospective clinical trials so that the optimal therapy can be determined.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jan 26, 2007