The small numbers of patients with SCLC seen by the surgeon represent fewer than 10% of all

patients with SCLC. Such patients have peripheral tumors with no nodal involvement or only hilar nodal

involvement, which would be classified as Tl–2 N0–l (stage I or II) tumors in the TNM staging system.

In the past, such tumors were often diagnosed at exploratory thoracotomy for an asymptomatic coin

lesion, but with the increasing use of diagnostic percutaneous needle aspiration, more patients with

early-stage SCLC are now identified preoperatively. Such patients should be evaluated in a

multidisciplinary setting in conjunction with medical and radiation oncology, and resection should be

considered after distant disease has been excluded. For such potentially operable patients, it has been

suggested that the TNM classification be used in future trials and studies.170,171

Retrospective series have demonstrated a 5-year survival rate of 30% to 50% after resection of T1 N0

or T2 N0 SCLC.170,172,173 Because of the propensity for small cell cancers to disseminate, adjuvant

chemotherapy has traditionally been given to patients although no prospective, randomized trials have

demonstrated whether this is of any benefit, due to the small numbers of patients available.173 Relapse

at the primary site, which is a problem for most patients with LS SCLC, is distinctly uncommon after

complete resection of these early tumors.174 Radiation therapy to the chest has been suggested after

complete resection, but because insufficient information is available in the literature, and local relapse

is uncommon, this is not considered standard treatment.172,173 Given the propensity for patients to

develop brain metastases, prophylactic cranial irradiation is recommended for patients with either LSor ES SCLC with good performance status and who have completed initial therapy with either complete

or partial response.175

As the role of resection in patients with mediastinal nodal involvement (N2 disease) is questionable,

mediastinoscopy or EBUS should be considered mandatory to exclude mediastinal nodal disease.176 This

should be performed separately from thoracotomy since it can be difficult for the pathologist to

diagnose small cell cancer on a frozen section. The intraoperative management of SCLC is not

significantly different from that of NSCLC, and an incomplete resection does not benefit the patient.

The addition of resection after response to induction chemotherapy has been proposed by some

surgeons to cure a small number of patients with LS SCLC without mediastinal involvement.177 To date,

the LCSG has performed the only prospective, randomized trial evaluating the role of surgery in LS

SCLC.178 All patients enrolled in this study received induction chemotherapy. Objective responders were

randomized either to lung resection followed by thoracic and cranial radiation or to radiation therapy

alone. Because the survival rate was the same in both groups, with 2-year overall survival of 20%, this

trial did not support the addition of pulmonary resection to the multimodality treatment of SCLC. More

recently retrospective studies suggest better long-term survival, in selected patients with stage I SCLC,

of over 50% at 5 years.171

Finally, the occurrence of a second primary lung carcinoma after treatment for SCLC has been

reported in the few patients with prolonged survival. It should not be assumed that the new tumor is of

small cell histology, and these patients should be evaluated for the possibility of resection.179 The

average risk for the development of a second lung cancer in patients who survive SCLC is approximately

6% per patient per year.83

Bronchial Gland Carcinomas

Bronchial gland carcinomas are rare primary tumors of the lung. They constitute about 1% of all lung

neoplasms and 2% of the tumors for which resection is performed. These tumors are also called primary

salivary gland-type tumors of the lung because the tracheal and bronchial airway submucosa and the

salivary glands contain serous and mucous glands that are histologically similar.180 Often, they are

called bronchial adenomas, but this term is misleading because they are malignant. Care must be taken to

separate these primary tumors from metastases of primitive salivary gland tumors.181 This group of

carcinomas includes adenoid cystic carcinoma, mucoepidermoid carcinoma, and the even rarer mixed

tumor (pleomorphic adenoma). The only truly benign tumors are mucous gland adenomas.

The symptomatology of these tumors is determined essentially by their location and size.181

Peripheral tumors, which are less frequent, are asymptomatic, generally presenting as a nodule on

routine chest radiography. Proximally located tumors present with symptoms of bronchial irritation and

obstruction, including cough, shortness of breath, hemoptysis, recurrent infection, wheezing, and

stridor. Sometimes, patients have constitutional symptoms, such as weight loss and pain. On chest

radiography, the nodule may be seen with pneumonia or atelectasis. Because of the slow growth of

these tumors, signs and symptoms may develop over a period of years. Incompletely obstructing tumors

frequently masquerade as asthma for prolonged periods of time. Smoking does not seem to be a risk

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factor for these tumors.

Peripheral tumors are diagnosed by percutaneous needle aspiration biopsy or by wedge resection at

the time of operation. Endobronchial tumors are diagnosed by bronchoscopy. Other studies, such as CT,

are rarely required to make the diagnosis but may be of value in planning therapy. Because most of

these tumors do not metastasize, complete excision, with preservation of as much pulmonary tissue as

possible, is the goal. Whenever possible, sleeve resections of main bronchi are performed to preserve

pulmonary tissue.

Adenoid Cystic Carcinoma

Adenoid cystic carcinomas are slowly growing malignant tumors that arise from the submucosal glands

of the trachea and main bronchi (Fig. 79-8). They have also been called cylindromas, adenoid cystic basal

cell carcinomas, adenomyoepitheliomas, and pseudoadenomatous basal cell carcinomas. Adenoid cystic

carcinomas behave much like the major and minor salivary gland tumors of the same name, to which

they are microscopically identical. An important aspect of their clinical behavior is that they tend to

spread in the submucosal plane along the perineural lymphatics, well beyond the obvious endoluminal

component of the tumor (Fig. 79-9). In a small biopsy specimen, it can be difficult to distinguish

adenoid cystic carcinoma from a conventional adenocarcinoma. Immunohistochemical stains may help

the pathologist differentiate the two by showing the presence of the myoepithelial cell

immunophenotype in adenoid cystic carcinoma.181

Figure 79-8. Tracheogram demonstrating airway obstruction by an adenoid cystic carcinoma of the upper trachea.

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Figure 79-9. Adenoid cystic carcinoma. A photomicrograph shows perineural infiltration by the tumor. From Rubin E, Farber JL.

Pathology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999.

Whenever possible, total excision by tracheal resection or tracheobronchial resection is the treatment

of choice.182–185 This is not always possible because of the extensive submucosal spread of tumor. In

such cases, the tumor should be resected with grossly negative margins along with adjuvant radiation

since these tumors are radiation-sensitive.

When resection is not feasible because of the extent of the lesion or the functional status of the

patient, a palliative treatment option is endoscopic laser removal followed by radiation (brachytherapy,

external beam irradiation, or both). When complete resection is possible, the prognosis is excellent.

However, because of the slow-growing nature of the tumor and its responsiveness to radiation,

prolonged survival is possible even with incomplete resection or palliative measures. Patients frequently

live 10 years or more with persistent disease, including pulmonary metastases. In such cases, repeated

efforts at palliation are indicated.

Mucoepidermoid Carcinoma

Mucoepidermoid carcinomas may be low- or high-grade malignancies and have the same microscopic

appearance as mucoepidermoid tumors of salivary gland origin. These tumors also arise in the glandular

submucosa, presenting as submucosal lesions. The distinction between a low-grade and high-grade

tumor is based on mitotic activity, cellular necrosis, and nuclear pleomorphism.180

The principles of treatment of mucoepidermoid tumors are similar to those of carcinoid tumors. The

more malignant variety must be treated as a bronchogenic carcinoma. Some authors even think that

adenosquamous carcinoma is the same entity as mucoepidermoid carcinoma, but arising in the

periphery of the lung.180 The outlook for these tumors depends on the grade of malignancy and the

stage of the disease. High-grade tumors have the same prognosis as bronchogenic carcinoma. Complete

resection is the mainstay of treatment. Mucoepidermoid tumors are too rare to permit an evaluation of

combined modality therapy for more aggressive, high-grade tumors.180

Mucous Gland Adenoma

Mucous gland adenomas are rare submucosal tumors that arise from mucous glands. They are also

known as bronchial cysts and papillary cystadenomas. Because of their totally benign behavior, they can

usually be treated by endoscopic excision. Thoracotomy and resection are indicated only if the distal

lung has been destroyed by chronic infection or if endoscopic removal is technically contraindicated or

incomplete.

OTHER MALIGNANT TUMORS OF THE LUNG

The lung is composed of epithelial, mesodermal, and endodermal cells, and malignant tumors may arise

from any of these cells. This group represents less than 1% of all primary lung cancers and is usually

subdivided into lymphoid tumors, soft-tissue sarcomas, mixed epithelial/mesenchymal tumors, and

ectopic tissue tumors.186,187 Primary pulmonary lymphomas usually are excised for confirmatory

diagnosis. Sarcomas arising from soft tissue or large vessels are treated in a similar fashion to sarcomas

occurring elsewhere. Treatment of the other rare tumors, including pulmonary blastomas, primary

melanomas of the bronchus, and malignant teratomas, primarily involves complete resection. Radiation

and chemotherapy do not have well-defined roles in the treatment of any of these tumors but are

occasionally used in particular situations.

RESECTION OF PULMONARY METASTASES

Historical Background

The first report of the resection of a pulmonary metastasis performed as a separate procedure is

attributed to Divis in 1926. In North America, the most quoted case of lobectomy for a metastatic

carcinoma was that performed by Barney and Churchill in 1939.188 Their patient underwent

nephrectomy for an adenocarcinoma and was known to have a pulmonary mass. After the renal

resection, the pulmonary tumor did not respond to radiation treatment and increased in size. Following

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exploration and resection of the pulmonary lesion, the patient survived disease-free for more than 20

years.

From 1940 to the mid-1960s, pulmonary metastasectomy was performed infrequently and only in

highly selected patients. A total of 169 pulmonary metastasis resections were performed on 165 patients

at the Mayo Clinic from 1941 to 1959.189 This large number of operations may reflect the high volume

of cases seen at the Mayo Clinic rather than the common use of resection at that time. The first

principles of pulmonary resection for metastatic disease included complete removal of the primary

disease, no evidence of recurrent or metastatic disease other than the lung lesion, and that the patient

was in good general condition. Multiple lesions were not considered a contraindication to resection (Fig.

79-10), but it was thought that bilateral disease indicated a poor prognosis and should not be resected.

Surgeons were already convinced that the resection should be as conservative of lung function as

possible.

Since then, experience from several institutions suggested that more liberal indications for pulmonary

metastasectomy are appropriate.190 A striking example was the treatment of metastatic osteogenic

sarcoma at Memorial Sloan-Kettering Cancer Center. From 1940 to 1965, only five such patients were

treated surgically. During the same period, only 24 of 145 patients (17%) survived 5 years after

resection of their primary tumors, and 118 of these patients (81%) died of pulmonary metastases. This

experience prompted a more aggressive approach to the management of pulmonary metastases. Starting

in 1965, a consecutive series of 22 patients with osteogenic sarcoma underwent pulmonary

metastasectomy. Patients were considered for operation even if they had bilateral metastases or

required multiple thoracotomies to remove all gross tumor. A total of 59 thoracotomies were performed

in these 22 patients, with an overall 5-year survival rate of 32%. The dramatic improvement in survival

in comparison with the historical experience strongly supported the aggressive use of pulmonary

metastasectomy in these patients.191

Figure 79-10. Metastatic carcinoma of the lung. A section through the lung shows numerous nodules of metastatic carcinoma,

corresponding to “cannon ball” metastases seen radiologically. From Rubin E, Farber JL. Pathology. 3rd ed. Philadelphia, PA:

Lippincott Williams & Wilkins; 1999.

During the past 30 years, resection has become a widely accepted treatment for certain pulmonary

metastases; however, some of the criteria for patient selection remain controversial. In addition,

advances in chemotherapy have changed the indications for resection. With some cancers, pulmonary

metastasectomy is performed to prolong life expectancy, whereas with others, it serves mainly to

restage disease or to provide adjuvant treatment after initial chemotherapy. The role of pulmonary

metastasectomy will undoubtedly continue to evolve as improvements in systemic treatment are made.

Clinical Presentation and Diagnosis

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Metastases are asymptomatic 85% of the time and are usually detected on a routine chest radiograph.

Patients who undergo resection of a primary tumor with a known tendency to metastasize to the lung

should have a chest radiograph as part of their routine follow-up care. On chest radiograph, metastases

usually present as well-circumscribed, spherical solid masses with well-defined borders (Fig. 79-11).

Cavitation is occasionally seen in large lesions with central necrosis, mostly squamous cell cancers. The

distribution of lung metastases is predominantly subpleural or in the outer-third of lung fields.192

Metastases to the lung usually arise in the pulmonary parenchyma. Endobronchial metastases are

uncommon but occur most typically with renal cell, colon, and breast cancers. Even with endobronchial

metastases, half of patients are asymptomatic.193 More often, endobronchial disease represents an

extension of contiguous parenchymal disease. The extent of endobronchial tumor can affect the

approach to resection. For these reasons, bronchoscopy should be performed before thoracotomy,

especially if centrally located metastases are present.

Figure 79-11. Chest radiograph of a patient with bilateral pulmonary metastases from endometrial cancer. The mass in the right

upper lobe is well circumscribed and has the radiographic appearance typical of a metastasis.

Hilar or mediastinal nodal involvement sometimes accompanies pulmonary metastases. Several

retrospective series have indicated that metastatic nodal involvement is a poor prognostic indicator,

independent of disease-free interval or number of nodules.194,195 However, the determinants of nodal

involvement and the prognostic and therapeutic implications remain poorly understood. Lymphangitic

spread can occur with or without concomitant pulmonary nodules. This happens most frequently in

breast cancer and produces a characteristic radiographic appearance of diffusely increased interstitial

markings and a clinical presentation of severe dyspnea that is out of proportion to the radiographic

findings.

When pulmonary metastases are thought to be present on a chest radiograph, CT should be performed

to determine their number, location, size, and potential resectability. Plain chest radiographs detect

only lesions at least 9 mm in size. New lesions of this size seen on a chest radiograph in a patient

already treated for a malignancy have a 90% chance of being malignant.196 Even though CT can identify

lesions as small as 3 mm, it often underestimates the number of pulmonary metastases (Fig. 79-12).

When radiologic and surgical findings are correlated, only 75% of malignant nodules are detected by

CT. Fifteen percent of CT studies overestimate the number of lung metastases for an accurate radiologic

assessment of 61%.197,198 FDG–PET scan appears to have a role as well in the preoperative evaluation of

resectable pulmonary metastases, enhancing the detection of extrathoracic or mediastinal involvement

that might preclude complete resection.199

8 Patients who present with multiple pulmonary nodules in the setting of a previously treated

malignancy rarely pose a diagnostic dilemma. Patients who present with solitary pulmonary nodules are

more problematic. Generally, a solitary lesion is more likely to be a metastasis if the primary tumor was

a sarcoma or a melanoma. If the primary tumor originated in the head, neck, or breast, it is more likely

to be a new primary lung cancer.200 It has an equal chance of being a metastasis or a new primary if the

initial tumor was of gastrointestinal or genitourinary origin. Percutaneous fine-needle aspiration biopsy

usually yields a tissue diagnosis, but the necessity of a biopsy in the case of a solitary lesion is

questionable. If the patient fits the criteria for resection, a biopsy of the lesion is best performed as an

2260

excisional biopsy. Because the findings on needle biopsy do not alter the recommendations for excision

of a solitary lesion, this procedure should be undertaken only if the patient is not an operative

candidate, if an alternative method of treatment is indicated, or if the patient requests that the diagnosis

be established before consenting to operation.

Figure 79-12. Imaging studies from a patient with metastatic embryonal rhabdomyosarcoma. Chest radiographs show a mass in

the right lower lobe (arrow, A) that is best seen on the lateral view (arrow, B). Computed tomography (CT) confirmed the presence

of this mass (arrow, C) and showed an additional nodule in the left upper lobe (arrow, D). At surgical exploration, however,

multiple bilateral pulmonary metastases were found that measured less than 5 mm and therefore were not seen on CT.

Criteria for Resection

The disease-free interval, number of metastatic nodules and tumor doubling time all have been used as

criteria for the resection of pulmonary metastases. Each of these remains controversial with respect to

its effect on long-term outcome.201 The disease-free interval is defined as the time from resection of the

primary tumor to the diagnosis of metastases. The length of the disease-free interval is thought to be of

prognostic significance and varies greatly among published reports from 7 months to 5 years.202

The number of metastatic nodules resected has also been considered predictive of survival. In

sarcomas, some have reported that the presence of four nodules is a significant breakpoint in survival;

however, the significance of the number of nodules varies among reported series. Most consider the

completeness of resection the best predictor of survival.203 Obviously, when a shower of numerous, tiny

(1 to 2 mm) lesions is encountered, complete resection is not possible.

Tumor doubling time is a measure of the aggressiveness of tumor growth. The prognostic importance

of tumor doubling time, however, is questioned because various doubling times, from 20 to 136 days,

have been found to be significant in different studies.202 Many do not consider this a criterion for

resection. The disease-free interval, number of metastatic nodules, and tumor doubling time in fact

reflect the intrinsic tumor biology.

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