Sandbox:Mazia

Overview

History Patients with Pancoast syndrome 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. The symptoms are typical of the location of the tumor in the superior sulcus or thoracic inlet adjacent to the eighth cervical nerve roots, the first and second thoracic trunk distribution, the sympathetic chain, and the stellate ganglion.

Initially, localized pain occurs in the shoulder and vertebral border of the scapula. Pain may later extend along an ulnar nerve distribution of the arm to the elbow and, ultimately, to the ulnar surface of the forearm and to the small and ring fingers of the hand (C8). If the tumor extends to the sympathetic chain and stellate ganglion, Horner syndrome and anhidrosis develop on the ipsilateral side of the face and upper extremity.

The pain is frequently relentless and unremitting, and adequate relief often requires administration of narcotics. The patient usually supports the elbow of the affected arm in the hand of the opposite upper extremity to ease the tension on the shoulder and upper arm.

The hand muscles may become weak and atrophic, and the triceps reflex may be absent. The first or second rib or vertebrae may be involved by tumor extension and intensify the severity of pain. The spinal canal and spinal cord may be invaded or compressed, with subsequent symptoms of spinal cord tumor or cervical disk disease.

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 et al, symptoms lasted 2-36 months, with a mean of 9.7 months. [7] In 1997, Muscolino described plexopathy or radicular symptoms in 53% of 15 patients. [24]

Historical Perspective

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

• [Disease name] may be classified according to [classification method] into [number] subtypes/groups:

• [group1]
• [group2]
• [group3]

• Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

Pathophysiology

• The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
• The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
• On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Causes

• [Disease name] may be caused by either [cause1], [cause2], or [cause3].
• [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for [disease name].

Differentiating [disease name] from other Diseases

• [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

Epidemiology and Demographics

• The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

Physical Examination

• Patients with [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

• There are no [imaging study] findings associated with [disease name].

• [Imaging study 1] is the imaging modality of choice for [disease name].
• On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
• [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.

• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

• There are no primary preventive measures available for [disease name].

• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

References

Pancoast syndrome (Pancoast’s syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung (lung cancer) leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3] This is accompanied by the following:

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 Atrophy of hand and arm muscles Horner syndrome ( ptosis, miosis, hemianhidrosis, enophthalmos) Compression of the blood vessels with edema Most Pancoast tumors are squamous cell carcinomas (SCCs) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.

Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [4] 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:

Extension of the tumor into the neck or vertebrae Presence of substantial mediastinal lymph nodes 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. [5]

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:

Intercostal nerves Lower roots of the brachial plexus Stellate ganglion Sympathetic chain 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. [6] (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. [7]

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.

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. [7] 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:

Desmoid tumors [8] Hemangiopericytoma [9] Adenoid cystic carcinoma [10] Metastatic carcinoma [11] Lymphoma [12] Thyroid carcinoma [13] Bacterial [14, 15] and fungal infections [16, 17] Lymphomatoid granulomatosis Vascular aneurysms Amyloid nodules Cervical rib syndrome Inflammatory pseudotumor (plasma cell granuloma) Mycotic subclavian artery aneurysm Carotid pseudoaneurysm in a child (caused by a hydatid cyst) Risk factors are similar for almost all lung cancers and include the following:

Prolonged asbestos exposure Exposure to industrial elements (eg, gold, nickel) Tobacco smoking Secondary smoke exposure 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). [18, 19] 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:

Presence of Horner syndrome Involvement of mediastinal lymph nodes Incomplete resection Involvement of supraclavicular lymph node 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. [20]

Overall survival data were summarized by Detterbeck, who noted that 5-year survival rates ranged from 15% to 56%. [21] Of the 104 patients treated by Attar and coworkers, 7 (~7%) were 5-year survivors and 3 (~3%) were 10-year survivors. [20] Another study demonstrated surgical morbidity rates of 7-38%, with mortality ranging from 5% to 10%. [22]

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 [23] :

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 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 a left superior sulcus location 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. [18]

This distribution of relapses was noted in several studies reviewed by Detterbeck. In many of these studies, patients received preoperative radiation therapy. [21] 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. [18]

Pancoast syndrome (Pancoast’s syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung (lung cancer) leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion). [1, 2, 3] This is accompanied by the following:

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 Atrophy of hand and arm muscles Horner syndrome ( ptosis, miosis, hemianhidrosis, enophthalmos) Compression of the blood vessels with edema Most Pancoast tumors are squamous cell carcinomas (SCCs) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.

Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers. [4] 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:

Extension of the tumor into the neck or vertebrae Presence of substantial mediastinal lymph nodes 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. [5]

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:

Intercostal nerves Lower roots of the brachial plexus Stellate ganglion Sympathetic chain 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. [6] (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. [7]

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.