January 17, 2007

Pancoast Syndrome

Synonyms and related keywords: superior sulcus tumor, Ciuffini-Pancoast syndrome, Ciuffini-Pancoast-Tobías syndrome, Hare's syndrome, Pancoast's apex syndrome, Pancoast's disease, Pancoast's pain syndrome, Pancoast-Tobías syndrome, Tobías' syndrome, Horner syndrome, Bernard-Horner syndrome, ptosis, miosis, hemianhidrosis, anhidrosis, enophthalmos, non–small cell lung cancer, NSCLC, non–small cell bronchogenic carcinoma, squamous cell carcinoma, SCC, adenocarcinoma, shoulder pain, Pancoast tumor, malignant neoplasm


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.


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:


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. A recent case report noted an interval of 3.5 years from onset of symptoms to diagnosis (No authors listed, 2000). 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.


Lung Cancer, Non-Small Cell
Lung Cancer, Oat Cell (Small Cell)

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 (No authors listed, N Engl J Med, 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.


Imaging Studies:


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

StageT (tumor)N (nodes)
T4Any 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.


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:


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

Drug Category: Antineoplastic agents -- 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
Cisplatin (Platinol) -- Alkylating agent causing intrastrand and interstrand cross-linking of DNA, leading to strand breakage. Has broad range of antitumor activity. Forms backbone of currently available approved combination chemotherapy regimens for NSCLC and SCLC that cause Pancoast syndrome.

Administered by IV infusion in isotonic sodium chloride solution (0.9%) or sodium chloride and glucose. The manufacturers recommend that higher doses be administered in 2 L of chloride-containing infusion fluid over at least 1-2 h and that an infusion time of 6-8 h may further reduce toxicity. In practice, volumes of less than 2 L have been used in expert centers. To aid diuresis and protect the kidneys, 37.5 g of mannitol (eg, 375 mL of mannitol [10%]) is usually added to the infusion, or is infused separately, immediately before cisplatin. In order to initiate diuresis, the patient is usually hydrated by the infusion of 1-2 L of a suitable fluid over several hours before the administration of cisplatin. Adequate hydration must also be maintained for up to 24 h after a dose. Renal, hematological, auditory, and neurological function should be monitored during therapy and administration adjusted accordingly.

Adult DosePE (cisplatin-etoposide) regimen: 25 mg/m2 IV on days 1-3 of cycle; repeat q3-4wk for 4-6 cycles
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment
InteractionsIncreases toxicity of bleomycin and ethacrynic acid; other nephrotoxic drugs (eg, aminoglycosides, amphotericin B, cyclosporine) increase nephrotoxicity; bleomycin, cytarabine, methotrexate, and ifosfamide may accumulate owing to decreased renal excretion; may worsen cytotoxicity of etoposide; mesna and sodium thiosulfate directly inactivate cisplatin; dipyridamole increases cytotoxicity by enhancing cellular uptake; paclitaxel-related peripheral neuropathy may be increased in patients previously treated with cisplatin
Pregnancy D - Unsafe in pregnancy
PrecautionsAdminister adequate hydration before and for 24 h after cisplatin dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur; peripheral blood cell counts and serum electrolyte levels should be monitored; requires close monitoring of pretreatment creatinine level and CrCl and posttreatment magnesium levels; neurologic examination should be performed regularly; major dose-limiting toxic effect is peripheral neuropathy; can cause acute or chronic renal failure in up to one third of patients treated, but this can usually be prevented by vigorous hydration and saline diuresis; renal tubular wasting of potassium and magnesium is common (monitor closely); cellulitis and fibrosis have rarely occurred after extravasation; avoid aluminum needles
Drug Name
Etoposide (Toposar, VePesid) -- 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 DosePE 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 DoseNot established
ContraindicationsDocumented hypersensitivity; IT administration (may cause death)
InteractionsMay 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
PrecautionsBleeding, severe myelosuppression, nausea, vomiting, hypotension, allergic reaction, and alopecia may occur; reduce dose in hepatic (eg, increased TB) or renal (eg, decreased CrCl) impairment



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