Adult Chest Surgery

Chapter 80. Benign Lung Masses 

A benign lung mass is defined as one that neither metastasizes nor invades surrounding tissue planes. The overall incidence of benign lung lesions is low. The classic study of Martini, which investigated the Memorial Sloan-Kettering experience, showed that less than 1% of resected lung lesions are benign.Indeed, sometimes the distinction between benign and malignant lesions is blurred. Therefore, the evaluation and correct characterization of an indeterminate pulmonary nodule is invaluable because it will determine further treatment plans and prognosis of the patient.


The solitary pulmonary nodule is a rounded lesion with well-demarcated margins. Its size may vary from a few millimeters to a few centimeters. Two features are particularly helpful in making the distinction between benign and malignant lesions: (1) Nodules with doubling times of less than 10 days or more than 450 days are most likely benign, and (2) calcifications seen on a chest radiograph or CT scan with fine cuts through the tumor that exhibit a central, diffuse, speckled, laminar, or popcorn pattern most likely reflect a benign mass, whereas eccentric calcifications are more characteristic of malignancy. Various diagnostic modalities have been used in attempts to differentiate between benign and malignant lung masses.


CT has been used to identify differences between primary lung cancers and benign nodules. Cancers were found to have an ill-defined tumor margin and spiculation, to involve bronchi or vessels, and to enlarge more rapidly than benign tumors.CT also can be used for guided percutaneous core needle biopsy of accessible pulmonary nodules. In a recent study of 60 patients with benign pulmonary lesions, percutaneous core needle biopsy was able to provide definitive diagnosis in 81.7% of cases as opposed to fine-needle aspiration, in which a specific benign diagnosis was made in only 16.7% of cases.Recent reports also have shown that 1-mm-thick slices on high-resolution CT can be used to differentiate between benign and malignant solitary pulmonary nodules with a sensitivity of 91.4%.4


Dynamic MRI is a modality that demonstrates significant kinetic and morphologic differences in vascularity and perfusion between benign and malignant solitary lung nodules. Malignant lesions show stronger enhancement and higher maximum peak signals than benign lesions.5


In addition, the use of fluorodeoxyglucose PET scanning has facilitated the determination of malignancy in nodules as small as 6 mm.If the nodule is glucose-avid and has a standardized uptake value of 2.5 or greater, it has a greater than 90% probability of being malignant. PET scanning can distinguish malignant from benign nodules with a sensitivity of 90%.Unfortunately, the sensitivity seems to decrease for nodules smaller than 10 mm in size. Similarly, the use of technetium-99m single-photon-emission CT and, more recently, methionine-based PET scanning has improved our ability to distinguish benign from malignant lung nodules. PET scanning is developing into an excellent tool for the diagnosis and staging of patients with thoracic malignancies, and it has been shown to be superior to CT in this respect.7


More recently, somatostatin-receptor scintigraphy with the new somatostatin analog technetium-99m depreotide has shown significant promise for discriminating between malignant and benign lung lesions. In a pilot study, 17 of 21 patients with high focal uptake of the marker were proved to have malignancies.8


Many potential markers of malignant behavior have been evaluated by immunohistochemistry in an attempt to better classify neoplastic proliferations. 15-Lipoxygenase-2, for example, is an arachidonic acid-metabolizing enzyme with expression levels that show an inverse correlation with tumor grade in several subtypes of lung carcinoma. This relationship suggests potential utility in differentiating benign from malignant epithelial lesions.9Similar results also were obtained with glutathione-metabolizing enzymes.

Moreover, serum biomarker assays show promise as an adjunct to imaging and other screening studies. In one report, serum immunoassays targeting cytokeratin fragment marker (CYFRA 21–1) and neuron-specific enolase exhibited a specificity of 100% in differentiating benign from malignant solitary pulmonary nodules,10 and the combination of these two tumor markers with carcinoembryonic antigen resulted in greater sensitivity and diagnostic accuracy. Tumor markers, when used alone or in combination with the new imaging techniques, brought no additional benefits in terms of sensitivity and accuracy over imaging methods alone. However, they exhibited a far superior specificity.11 Recent reports also have shown that progastrin-releasing peptide is a promising tumor marker for the detection and monitoring of small cell lung carcinoma, and an enzyme-linked immunoassay for its convenient measurement has already been developed.

Serum proteomic screening is another modality currently under investigation. Patient serum samples are examined for circulating protein tumor markers. Tumor protein expression patterns and markers may be detected and analyzed using a variety of techniques, including two-dimensional gel electrophoresis, antibody-based microarray, and mass spectrometry.12 Spectrometry in particular has been used successfully in screen-blinded serum samples to identify lung cancer patients with a sensitivity of 93% and a specificity of 97%.13

Proteomic analysis has also shown value in the classification and subclassification of tumors after tissue is obtained. While the current focus is largely on pulmonary malignancy, the ability to classify lesions by their protein expression patterns (e.g., protein types, quantities, and posttranslational modifications) ultimately may aid in identifying benign tumors. The techniques generally are the same as those used in serum screening. Spectrometry is often accomplished by surface-enhanced laser desorption/ionization mass spectrometry or matrix-assisted laser desorption/ionization time-of-flight methods. The difference in these systems is beyond the scope of this chapter, but they have been clearly reviewed in the literature.14 Matrix-assisted laser desorption/ionization time-of-flight methods permit direct analysis of frozen tissue sections, which are irradiated by laser beam in preselected areas of tumor. The protein signature generated is compared with protein profile databases from known tumors to help classify the unknown lesion.

Detection of malignancy by sputum screening also may be facilitated by molecular markers. The utility of heterogeneous ribonuclear protein B1 expression, for example, has been examined for its value in distinguishing benign from malignant lung masses because it appears to be overexpressed in a variety of lung carcinomas.15 In addition, transforming growth factor  has been shown to stimulate production of the erbB gene products at a much higher level in tumorigenic as compared with nontumorigenic lung epithelial cells.


Definitive diagnosis can be achieved only with excisional biopsy, most commonly performed by VATS or with thoracotomy. Nodules larger than 10 mm that are suggestive of malignancy or are indeterminate by other means of morphologic analysis have to be defined by surgical excision. Recent advances in minimally invasive surgery make the possibility of obtaining a definitive diagnosis with complete resection less daunting for both the patient and the surgeon.

In this chapter we have tried to approach the multitude of benign lung masses in a systematic way. We have divided lesions into those that occur primarily in an endobronchial location and those that are found mostly in an intraparenchymal position. Hamartomas are examined separately because of their high incidence compared with other benign lung lesions and because they occur both endobronchially and intraparenchymally. In the study of each tumor type, an effort has been made to analyze it on the basis of demographics, clinical presentation, histology, imaging or bronchoscopic appearance, and finally, treatment options. Also, within each major division, we have further categorized the tumors according to the type of cell from which they originated.


The most common benign lesion of the lung is the hamartoma. It accounts for more than 70% of all benign lung tumors16 (see the description in Chap. 79). Rarely, a pulmonary hamartoma is found with a gastric leiomyosarcoma and a functioning extraadrenal paraganglioma comprising what is known as Carney's triad. Hamartomas represent abnormal arrangements of mature mesenchymal tissue types normally found in the lung. Most commonly, pulmonary hamartomas include a cartilaginous component, but fibrous elements, adipose tissue, and smooth muscle are also seen (Fig. 80-1).

Figure 80-1.


Photomicrograph of a hamartoma indicating the presence of cartilage.


Radiographically, hamartomas appear as smooth, lobulated, well-circumscribed peripheral lesions most often located in the lower lung fields with diameters ranging from 1 to 3 cm and increasing at a mean rate of 3–5 mm per year (Fig. 80-2). Popcorn-like or diffuse calcifications can be seen in 10–30% of radiographs of hamartomas. Endobronchial lesions are seldom detected radiographically, unless there are concomitant lung parenchymal changes such as atelectasis, pneumonia, or abscess formation.

Figure 80-2.


A left upper lobe hamartoma.

On CT scan, calcifications associated with hamartomas are detected only 5% of the time. The presence of fatty tissue in a peripheral solitary lesion identified on CT scan is highly suggestive of a hamartoma. However, fatty tissue identification occurs in only 50% of cases. The general appearance of a hamartoma on CT scan is consistent with a smoothly marginated mass with mixed fat and soft tissue attenuation. The treatment of hamartomas is described in Chapter 80.


Tumors of Epithelial Origin


A papilloma most commonly presents as a solitary endobronchial tumor less than 1.5 cm in size in men with an extensive smoking history, usually in the fifth and sixth decades of life. These lesions are usually located endobronchially and produce obstructive symptoms. In children, on the other hand, they are usually seen in association with laryngeal papillomatosis involving the vocal cords or the trachea. They present as multiple squamous papillomas that carry a risk of malignant degeneration and usually require surgical excision. Human papillomavirus serotypes 16 and 18 have been implicated as etiologic factors17 (Fig. 80-3).

Figure 80-3.


Photomicrograph of a right main stem bronchial papilloma.

Papillomas can be divided into three histologic categories based on their epithelial surface: squamous, glandular (columnar), and mixed. Most respiratory tract papillomas are of the squamous type. Papillomas associated with human papillomavirus serotypes 16 and 18 tend to show dysplasia and an increased tendency to become malignant. Furthermore, the lesions of viral respiratory tract papillomatosis are more likely to invade local tissues. Glandular papillomas must be distinguished from well-differentiated adenocarcinoma.

Papillomas are diagnosed bronchoscopically from their typical papillary appearance. Treatment is usually laser ablation or endoscopic removal unless malignancy develops, which usually requires bronchotomy and a sleeve resection. Photodynamic therapy also has been used with some success to treat multiple laryngotracheobronchial papillomas. A nonresectional treatment approach mandates regular bronchoscopic follow-up with biopsies.


This lesion arises primarily from the submucosal mucus glands of a lobar or segmental bronchus of the lower lobes and can be seen in both children and adults. These tumors usually are encapsulated and easily separated from the bronchus. Most patients are symptomatic and present with fever, hemoptysis, chest pain, recurrent pneumonia, or persistent cough. If there is no bronchial obstruction, the patient is asymptomatic.

Cystic change is a critical diagnostic feature of these lesions with cysts containing mucinous or serous contents. Other criteria for diagnosis include an endobronchial location, exophytic growth superficial to the cartilaginous plate, and the presence of at least some normal-appearing bronchial gland mucinous epithelium. Mucoepidermoid carcinoma sometimes can mimic a benign mucus gland adenoma. The immunophenotype varies from tumor to tumor, but epithelial membrane antigen, blood group substances, and keratin are frequently identifiable in the epithelium. Tumors also may express aberrant B blood group antigen (ABO system) in A- or O-type patients.18

On chest radiograph, adenomas appear as round, dense, well-demarcated nodules or as postobstructive pneumonitis, atelectasis, or consolidation. In some patients, the chest radiograph appears normal. On CT scan, they appear as round or oval masses that are heterogeneously low in attenuation and can be multicystic. Their size is widely variable, from as small as 2 cm to as large as 6 cm in diameter. Lesions can demonstrate an air-meniscus sign that suggests their expansive and endobronchial nature. Endoscopically, they appear as firm pink nodules with intact overlying epithelium or as lobulated, usually pedunculated endobronchial masses. A gelatinous coating over the surface of the tumor helps to distinguish it bronchoscopically from other lesions. Definitive diagnosis, however, can only be made with pathologic examination of the tissue.

Treatment is usually endoscopic removal with laser, cryotherapy, or curettage. Surgical resection is performed only if bronchoscopic removal is incomplete or if the distal lung parenchyma is destroyed. Wedge resection is commonly performed, but lobectomy may be necessary if there is irreversible damage to the distal lung tissue. Pneumonectomy should be avoided in children because it can interfere with the normal development of the thorax.19


Benign Endobronchial Histiocytoma

Benign endobronchial histiocytoma is a rare endobronchial lesion that occurs most commonly in children or young adults. In many cases these tumors belong to the broader category of inflammatory pseudotumor and may be composed of varying amounts of storiform fibroblasts, plasma cells, foamy histiocytes, and other inflammatory cells. They have no distinguishing radiographic features, and their exact incidence is unknown as a result of their rarity. They usually present with hemoptysis and can be associated with cavitation. Wide local excision is recommended owing to their low-grade potential for malignant degeneration.20 Bronchoplastic resection has been used successfully to treat these tumors.


Granular Cell Tumor

Granular cell tumors are rare benign tumors of the lung (Fig. 80-4). Approximately 75% of these tumors are solitary, 15% are solitary but found in association with multiple skin lesions, and 10% are multiple. In approximately 50% of patients, these tumors are discovered incidentally. In the other half, the tumors usually cause bronchial obstruction that leads to atelectasis, hemoptysis, or pneumonia. Granular cell tumors usually are sessile polyps that grow within the trachea or a central bronchus and are now known to be neural in differentiation. Although they are usually seen as tracheal or bronchial polyps, rare peripheral examples also have been reported. Histologically, the cells are usually polygonal and demonstrate ample eosinophilic cytoplasm with coarse granularity and small, bland nuclei. Ultrastructural and immunohistochemical evidence suggests schwannian differentiation, with positive immunohistochemical staining for neural markers such as S100, CD56, and myelin basic protein.21 The cytoplasm is filled almost entirely with secondary and tertiary lysosomes, which impart the classic pink cytoplasmic color on hematoxylin and eosin staining and can be identified by electron microscopy.

Figure 80-4.


Granular cell tumor photomicrograph.


On chest radiographs or CT scans they appear as coin lesions and may cause lobar infiltrates or lobar atelectasis (Fig. 80-5). They are usually circumscribed but not encapsulated and range in size from 0.3 to 5.0 cm. Treatment is conservative resection. Curative resection of recurrences also has been reported. More recently, laser therapy has been used with success for certain obstructing tumors.

Figure 80-5.


CT image of a granular cell tumor.


Tumors of Epithelial Origin


This lesion is usually peripheral in location and appears in both men and women who have a history of heavy smoking with approximately equal frequency. It appears to have a predilection for the right lung. It occurs in the fifth or sixth decade of life and usually is discovered incidentally on a chest radiograph.

This is a unilocular cystic lesion with a fibrous wall and mucinous contents. The relatively bland, cuboidal-to-columnar mucinous epithelium may be sparse or detached. There is no association of cystadenoma with larger airways, and it lacks the ciliated lining, bronchial glands, and cartilage of a bronchogenic cyst. Immunophenotypic and ultrastructural characteristics are nonspecific and of limited utility in the differential diagnosis. A cytokeratin 7-positive, cytokeratin 20-negative phenotype, however, may help to distinguish it from metastatic disease (Fig. 80-6).

Figure 80-6.


Photomicrograph of a mucinous cystadenoma.


On chest radiograph, cystadenomas are well-demarcated singular cystic masses located mostly in the periphery of the lung parenchyma. On CT scan, they appear as homogeneous masses with a smooth margin (Fig. 80-7).

Figure 80-7.


CT image of a mucinous cystadenoma.

Treatment is complete surgical excision with excellent prognosis. Since these lesions will harbor areas of cellular atypia, in situ malignancy, or invasive adenocarcinoma,22 complete excision is necessary, and careful postoperative histopathologic examination is imperative.


Alveolar adenomas are very rare, and the largest series reported in the literature consists of only a few patients. These tumors are, on average, 2 cm in diameter, well encapsulated, and can be shelled out easily from the surrounding lung parenchyma. They present more commonly in women between the fifth and seventh decades of life. Usually asymptomatic, most are discovered on routine chest radiograph. Patients can present with chronic, insidious cough, usually nonproductive, but shortness of breath or obstructive symptoms are rare.

These benign lesions arise from a joint proliferation of alveolar epithelium and septal mesenchymal cells. Grossly and microscopically, they are well circumscribed and multicystic. The epithelium is predominantly composed of type II pneumocytes. It is still unclear whether the mechanism of origin involves proliferation of a single primitive cell with dual differentiation or independent proliferation of both cell types. Alveolar adenoma must be distinguished clinicopathologically from atypical adenomatous hyperplasia (a preneoplastic lesion also confusingly called bronchioloalveolar adenoma), lymphangioma, and congenital adenomatoid malformation.

Alveolar adenomas usually are identified on routine chest radiographs as solitary nodules located in the midlung fields. The tumor margins are well demarcated, and they are usually noncalcified. On CT scan, they appear as small, homogeneous nodular areas of ground-glass opacity. A cystic component to the tumor sometimes can be seen on CT scan.

Definitive diagnosis by bronchoscopy is difficult because of the peripheral location of most tumors. Because the radiographic presentation of the tumor is nonspecific, definitive diagnosis requires accurate recognition of the characteristic histologic features of the tumor.

Surgical excision with open thoracotomy or VATS appears to be curative. Wedge resection is the procedure of choice, but lobectomy also has been reported (Fig. 80-8).

Figure 80-8.


CT image of an alveolar adenoma.


Pulmonary mixed tumors show a predilection for women, can appear at any age between the fifth and eighth decades of life, and usually have a parenchymal location but also can be endobronchial. The most common presenting symptoms include obstructive symptoms such as productive cough and fever. They tend to be slow growing and can reach significant size before they cause symptoms.

Histologically, they contain both stromal and epithelial components and are also found in the salivary glands. Although overexpression of oncogenes and tumor suppressor genes have been reported for the salivary gland variant, there is a relative scarcity of such reports for pulmonary pleomorphic adenomas. A high proliferative index and immunoreactivity to tumor suppressor gene p16 have been documented in one lung example.23

Chest radiography usually reveals a sharply defined density. CT scan or MRI reveals a well-circumscribed, homogeneous lesion ranging from 1.5 to 16 cm in size, usually with no mediastinal or hilar lymphadenopathy. Definitive diagnosis can be established with transbronchial biopsy.

Treatment of choice is complete surgical excision because if nests of tumor are left behind, they tend to recur. Recurrence can be seen as late as 9 years after the apparent complete tumor clearance and can present as either a recurrent lung lesion or as distant metastases, usually to the spine, liver, or breast. Implantation of tumor cells during the operation is considered to be one reason for this rare occurrence. Therefore, long-term surveillance is necessary. The treatment of choice for metastases in accessible sites appears to be surgical excision because the metastases are slow growing and may remain solitary for a long time. Radiation therapy can be used for palliation from bone metastases, but the tumor itself shows low susceptibility to radiation.



These benign tumors of the lung comprise 2% of all benign lung lesions and are found half the time in an endotracheal or endobronchial location and half the time in a parenchymal location. They are more common in females and in young adults.

Most endobronchial leiomyomas cause hemoptysis, which leads to their discovery. The parenchymal ones are usually discovered incidentally on a chest radiograph. The parenchymal lesions are solitary masses that have variable sizes. As in leiomyomas of other organs, pulmonary tumors show sweeping fascicles of bland spindle cells with moderate eosinophilic cytoplasm and cigar-shaped nuclei. They are typically well circumscribed (Fig. 80-9).

Figure 80-9.


Photomicrograph of leiomyoma at 100x magnification. The presence of smooth muscle cells is characteristic.

Occasionally, benign leiomyomas are observed in young women with uterine leiomyomas, and in these cases, they are considered metastasizing and can even prove fatal. Recent studies have demonstrated the presence of unique periglandular cells in the stroma of these metastasizing leiomyomas. These cells lack the conventional immunohistochemical characteristics of normal lung smooth muscle cells but stain positively for a variety of unique markers such as CD 10, CD 34, alpha smooth muscle actin, estrogen receptor, and progesterone receptor. It has been speculated that interactions of such cells actually may induce glandular metaplasia in the entrapped pulmonary epithelium seen in these tumors.

Treatment of metastasizing pulmonary leiomyomas requires surgical removal, chemotherapy, and hormonal manipulation. Recent approaches to hormonal manipulation with estrogen-receptor modulators and aromatase inhibitors have proved successful and have obviated the need for oophorectomy. Nonsurgical treatment is preferred if the nodules are multiple and diffuse.

The more common, nonmetastasizing endobronchial lesions are treated with endoscopic laser ablation, simple endoscopic removal, or sleeve bronchoplasty, provided that the distal lung tissue is not destroyed. Parenchymal leiomyomas are treated with complete surgical resection.

Intrapulmonary Fibrous Tumor

This tumor arises from the mesenchymal layer of the visceral pleura and extends into the lung parenchyma. These tumors, however, are not derived from the mesothelium, are not related to asbestos exposure, and do not show mesothelial differentiation. Nonetheless, when an intrapulmonary fibrous tumor is encountered, mesothelioma is the main differential diagnostic consideration.

Intrapulmonary lesions tend to be well circumscribed, with firm white cut surfaces. Histologic examination reveals that the tumors are composed of spindle cells with oval nuclei and diffuse fine chromatin, surrounded by dense bundles of collagen in less cellular areas. Variable cellularity and branching or "staghorn" blood vessels are common features helpful in the identification of intrapulmonary fibrous tumor. The cells stain for vimentin and CD 34,24 the latter of which is particularly helpful in excluding mesothelioma from the differential diagnosis.

The most characteristic radiographic finding of these lesions is the obtuse angle that they make with the chest wall, thus revealing that they arise from the pleura and not the lung. In fact, they have also been reported in the retroperitoneum, mediastinum, and on the parietal surface of the stomach or intestine. They can become quite large, although most are less than 10 cm in diameter.

Treatment is usually surgical resection, which is considered curative. Most commonly resection is done with VATS because most tumors are pedunculated, and their complete removal is easy. It is important to examine the resected tumor carefully after surgical excision because a malignant variant has been reported.


Cavernous Hemangioma

These are rare lung tumors that are thought to form from pulmonary arteriovenous malformations, and their presence raises suspicion of the possibility of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). MRI is the most accurate way to detect and evaluate them. Solitary lesions are surgically excised. If the lesion is endobronchial, a sleeve resection of the involved bronchus is indicated.

Sclerosing Hemangioma

This is a benign lung tumor, most likely of epithelial origin, with evidence of bronchiolar and alveolar pneumocyte differentiation. The tumor can present between the second and seventh decades of life and has a strong predilection for women. It is usually asymptomatic (75% of cases), but symptomatic patients present with chest pain, dyspnea, or hemoptysis. The tumor appears as a solitary nodule on chest radiography and is found most commonly in the lower lobes.

Typically sharply circumscribed, the tumor also may demonstrate multifocality or satellite nodules surrounding a large central lesion. Under the microscope, four basic architectural patterns may be identified: papillary, sclerotic, solid, and hemorrhagic. Round stromal cells and surface lining cells are present, and both may show immunoreactivity to epithelial membrane antigen. Complete surgical resection is curative, and although a minority may metastasize to regional lymph nodes, this does not seem to affect the overall prognosis.

Pulmonary Capillary Hemangiomatosis

This condition represents an aggressive benign tumor of the lung that consists of multiple capillaries proliferating slowly but diffusely in the lung parenchyma, involving the pulmonary vessels and the smaller airways in this proliferation. This results in the development of pulmonary hypertension and eventually in right-sided heart failure. The diagnosis can be made radiographically by observing the typical reticulonodular pattern that characterizes the affected lung. The only treatment available is bilateral lung transplantation because single-lung transplantation has been reported to be inadequate for treating this process.25


Inflammatory Pseudotumor (Inflammatory Myofibroblastic Tumor)

Inflammatory myofibroblastic tumor is an uncommon lesion of borderline malignant potential (low-grade malignancy). It is most likely caused by an excessive inflammatory response to tissue injury and it is frequently preceded by an upper respiratory tract infection. In fact, an organizing pneumonia can function as the nidus for formation of the pseudotumor. The lung is the most common site of occurrence, but it may be seen in the small and large bowel mesentery, omentum, mediastinum, retroperitoneum, and other locations.

Inflammatory myofibroblastic tumor usually presents in children and young adults with no sex or racial predilection. In appearance, it is a firm, nonencapsulated, white or yellow mass. Patients can present with cough, dyspnea, chest pain, wheezing, or hemoptysis. Fifty percent of cases are asymptomatic and can be detected by finding solitary nodules on routine chest radiographs or CT scans of the chest.

The mass size varies from 1 to 10 cm, and sometimes it is accompanied by hilar or mediastinal lymphadenopathy, pleural effusion, or distal atelectasis resembling bronchogenic carcinoma. Nevertheless, unlike bronchogenic carcinoma, inflammatory pseudotumors tend to be well circumscribed. Definitive diagnosis usually requires surgical biopsy.

Histologically, they are characterized by a mixture of spindle and inflammatory cells, including plasma cells. Immunohistochemically, the spindle cells express smooth muscle actin, vimentin, and sometimes activin-like kinase receptor 1 (ALK1). The inflammatory cells are polyclonal, which is a critical point in separating these tumors from lymphoma or plasmacytoma (Fig. 80-10).

Figure 80-10.


Photomicrograph of an inflammatory pseudotumor.

The tumors seem to follow two patterns of biologic behavior. One tumor group is aggressive, attains large sizes, has a higher number of inflammatory cells on histologic examination, and tends to invade adjacent structures such as the pulmonary vessels or the diaphragm. The other, more common group consists of tumors that tend to remain small, do not invade local tissues, and have a smaller number of inflammatory cells.

Treatment is complete surgical excision. Incomplete removal of the tumor may lead to recurrence. Overall prognosis is excellent. For unresectable or multiple lesions, radiation, chemotherapy, or steroids can be used with variable success. Spontaneous regression is seen occasionally in children.

Hyalinizing Granuloma

Hyalinizing granuloma is a rare benign pulmonary tumor of dense hyalinized connective tissue that develops in response to inflammation. Most patients have a previous history of fungal or mycobacterial infections that could induce tumor formation or a history of some autoimmune disease. The presence of hyalinizing granulomata also can follow systemic diseases such as multiple sclerosis or systemic idiopathic fibrosis. They can occur at any age from young adults to the elderly, and there is no sex predilection.

Patients either can be asymptomatic or present with a combination of cough, chest pain, dyspnea, and occasionally, weight loss. Lesions can be solitary or multiple but are usually bilateral. The tumor size is also highly variable from a few millimeters to several centimeters. Treatment is usually surgical excision (Fig. 80-11).

Figure 80-11.


CT image of a hyalinizing granuloma.


Nodular Amyloid

Nodular amyloid is part of a spectrum of amyloid lesions associated with the lung that includes a tracheobronchial amyloid type and a diffuse interstitial pulmonary amyloid type. Nodular amyloid is found most commonly in the lower lobes as single or multiple nodules of amyloid surrounded by giant cells and is not associated with systemic amyloidosis. Lesions also can be asymmetric and bilateral. Both sexes are equally affected, and the disease can present at any age, with the sixth and seventh decades of life being most common. The histologic appearance reveals eosinophilic deposits with "apple green" birefringence after staining with Congo Red and examination under polarized light. The nodules may calcify, or metaplastic bone or cartilage formation may occur, and inflammatory cells are often present in the background (Fig. 80-12).

Figure 80-12.


Nodular amyloid (H&E stain; 100x). Nodular deposits of amorphous, eosinophilic amyloid material (right) are surrounded by inflammatory cells, including multinucleate giant cells (bottom left).


Patients are usually asymptomatic, and the nodules are discovered incidentally on chest radiograph. However, the disease is rarely associated with multiple myeloma, and the presence of nodular amyloid always should raise suspicion and induce appropriate diagnostic workup for multiple myeloma (Fig. 80-13).

Figure 80-13.


CT image of a left lower lobe nodular amyloid lesion.

The lesion size can range from 0.4 to 15 cm, with an average size of 3 cm. Diagnosis can be established with bronchoscopic lung biopsy, although these patients do have an increased risk of postbiopsy bleeding.26

Surgical excision is considered curative. Long-term follow-up is necessary because of the reported association of nodular amyloid with macroglobulinemia and lymphoma. Laser therapy also has been employed successfully when patients with tracheobronchial amyloidosis present with obstructive symptoms.

Primary Pulmonary Thymoma

Primary pulmonary thymoma is a very rare tumor that arises in the lung of a patient with a normal thymus gland. The tumor most likely arises from embryologic descent of thymic tissue to a position more inferior than normal, but on occasion, it may arise from developmentally immature cells. The tumor exhibits a slight female preponderance and tends to occur in older patients with a mean age of 55 years. There is also some association with myasthenia gravis. Primary pulmonary thymomas can present with fever, retrosternal pain, nonproductive cough, malaise, and hemoptysis, but most patients are asymptomatic, and the tumor is often discovered incidentally on routine chest radiograph.

Intrapulmonary thymoma is identical histologically to a thymoma that arises in the mediastinum. Diagnosis is facilitated by immunohistochemistry, which permits identification of thymic-type T-cell antigens (CD3 and/or CD5) and other markers of immaturity (CD1a, TdT, or CD99). The epithelial component of the thymoma expresses cytokeratin, endomysial antibodies, and sometimes CD5. This epithelial and lymphoid immunophenotype can be critical in distinguishing primary pulmonary thymoma from other tumors in the differential diagnosis, namely, lymphoma or lymphoepithelial-like carcinoma of the lung.

Intrapulmonary thymomas can be located centrally, in a hilar location, or peripherally. The size of the lesion ranges from 1.7 to 12 cm. As in mediastinal thymomas, extension beyond the capsule suggests invasive behavior. Primary pulmonary thymoma has no distinctive radiographic features but appears as a well-circumscribed lesion confined in the lung. They are slow-growing lesions that remain asymptomatic until they cause bronchial obstruction.

Treatment is surgical excision. Prognosis is good in well-circumscribed, encapsulated lesions that are resected completely. The presence of an effusion does not preclude cure unless the pleura is directly involved by the tumor. In the rare case of an extensive, unresectable tumor involving the pleura, radiation therapy can be used with good results.


Despite their multitude, benign masses of the lung are rare and constitute only 1% of lung lesions resected. They are commonly silent clinically and are discovered incidentally on a chest radiograph. The most critical issue with a solitary pulmonary nodule is to differentiate it from a possible malignancy. In fact, benign lesions of the lung are often a diagnosis of exclusion during the evaluation of an indeterminate solitary pulmonary nodule. Over the last few years, significant progress has been made in our ability to perform this differentiation. Contrast-enhanced and high-resolution CT scanning, dynamic MRI, and PET scanning, along with the discovery of highly specific tumor markers and the recent use of serum proteomics, have allowed us to identify benign masses of the lung with much greater accuracy than ever before. This has led to greater confidence when we decide to observe a patient rather than proceed directly to an excisional biopsy. However, in many cases it is still necessary to perform either diagnostic or therapeutic surgical resection. In these patients, the recent advances in minimally invasive thoracic surgery that diminish morbidity have made this prospect much less daunting for both the surgeon and the patient.


This chapter provides a careful compilation of benign lung tumors. You are likely to come across at least one of these abnormalities in the course of your thoracic surgical career. Careful evaluation prior to resection can lead to a decision to perform lung-sparing surgery, possibly by VATS, thereby affording the patient an easier recovery.



1. Martini N: Results of Memorial Sloan-Kettering lung project. Recent Results Cancer Res 82:174–8, 1982. [PubMed: 6287545]

2. Ohtsuka T, Nomori H, Horio H, et al: Radiological examination for peripheral lung cancers and benign nodules less than 10 mm. Lung Cancer 42:291–6, 2003. [PubMed: 14644516]

3. Greif J, Marmor S, Schwarz Y, Staroselsky AN: Percutaneous core needle biopsy vs fine needle aspiration in diagnosing benign lung lesions. Acta Cytol 43:756–60, 1999. [PubMed: 10518126]

4. Iwano S, Makino N, Ikeda M, et al: Solitary pulmonary nodules: Optimal slice thickness of high-resolution CT in differentiating malignant from benign. Clin Imaging 28:322–8, 2004. [PubMed: 15471662]

5. Schaefer JF, Vollmar J, Schick F, et al: Solitary pulmonary nodules: Dynamic contrast-enhanced MR imaging—Perfusion differences in malignant and benign lesions. Radiology 232:544–53, 2004. [PubMed: 15215548]

6. Sarinas PS, Chitkara RK: PET and SPECT in the management of lung cancer. Curr Opin Pulm Med 8:257–64, 2002. [PubMed: 12055386]

7. Bury T, Dowlati A, Paulus P, et al: Evaluation of the solitary pulmonary nodule by positron emission tomography imaging. Eur Respir J 9:410–4, 1996. [PubMed: 8729997]

8. Baath M, Kolbeck KG, Danielsson R: Somatostatin receptor scintigraphy with 99mTc-depreotide (NeoSpect) in discriminating between malignant and benign lesions in the diagnosis of lung cancer: A pilot study. Acta Radiol45:833–9, 2004. [PubMed: 15690613]

9. Gonzalez AL, Roberts RL, Massion PP, et al: 15-Lipoxygenase-2 expression in benign and neoplastic lung: An immunohistochemical study and correlation with tumor grade and proliferation. Hum Pathol 35:840–9, 2004. [PubMed: 15257547]

10. Seemann MD, Beinert T, Furst H, Fink U: An evaluation of the tumour markers, carcinoembryonic antigen (CEA), cytokeratin marker (CYFRA 21-1) and neuron-specific enolase (NSE) in the differentiation of malignant from benign solitary pulmonary lesions. Lung Cancer 26:149–55, 1999. [PubMed: 10598925]

11. Seemann MD, Seemann O, Dienemann H, et al: Diagnostic value of chest radiography, computed tomography and tumour markers in the differentiation of malignant from benign solitary pulmonary lesions. Eur J Med Res 4:313–27, 1999. [PubMed: 10471543]

12. Maciel CM, Paschoal ME, Kawamura MT, Carvalho Mda G: Serum protein profiling of lung cancer patients. J Exp Ther Oncol 4:327–34, 2004. [PubMed: 15844662]

13. Xiao X, Liu D, Tang Y, et al: Development of proteomic patterns for detecting lung cancer. Dis Markers 19:33–9, 2003. [PubMed: 14757945]

14. Meyerson M, Carbone D: Genomic and proteomic profiling of lung cancers: Lung cancer classification in the age of targeted therapy. J Clin Oncol 23:3219–26, 2005. [PubMed: 15886309]

15. Snead DR, Perunovic B, Cullen N, et al: hnRNP B1 expression in benign and malignant lung disease. J Pathol 200:88–94, 2003. [PubMed: 12692846]

16. Arrigoni MG, Woolner LB, Bernatz PE, et al: Benign tumors of the lung: A ten-year surgical experience. J Thorac Cardiovasc Surg 60:589–99, 1970. [PubMed: 5511893]

17. Popper HH, el-Shabrawi Y, Wockel W, et al: Prognostic importance of human papilloma virus typing in squamous cell papilloma of the bronchus: Comparison of in situ hybridization and the polymerase chain reaction.Hum Pathol 25:1191–7, 1994. [PubMed: 7959664]

18. England DM, Hochholzer L: Truly benign "bronchial adenoma": Report of 10 cases of mucous gland adenoma with immunohistochemical and ultrastructural findings. Am J Surg Pathol 19:887–99, 1995. [PubMed: 7611535]

19. Lack EE, Harris GB, Eraklis AJ, Vawter GF: Primary bronchial tumors in childhood: A clinicopathologic study of six cases. Cancer 51:492–7, 1983. [PubMed: 6295603]

20. Bueno R, Wain JC, Wright CD, et al: Bronchoplasty in the management of low-grade airway neoplasms and benign bronchial stenoses. Ann Thorac Surg 62:824–8; discussion 828–9, 1996. 

21. Deavers M, Guinee D, Koss MN, Travis WD: Granular cell tumors of the lung: Clinicopathologic study of 20 cases. Am J Surg Pathol 19:627–35, 1995. [PubMed: 7755149]

22. Traub B: Mucinous cystadenoma of the lung. Arch Pathol Lab Med 115:740–1, 1991. [PubMed: 1863181]

23. Ang KL, Dhannapuneni VR, Morgan WE, Soomro IN: Primary pulmonary pleomorphic adenoma: An immunohistochemical study and review of the literature. Arch Pathol Lab Med 127:621–2, 2003. [PubMed: 12708911]

24. Chang YL, Lee YC, Wu CT: Thoracic solitary fibrous tumor: Clinical and pathological diversity. Lung Cancer 23:53–60, 1999. [PubMed: 10100146]

25. Eltorky MA, Headley AS, Winer-Muram H, et al: Pulmonary capillary hemangiomatosis: A clinicopathologic review. Ann Thorac Surg 57:772–6, 1994. [PubMed: 8147666]

26. Strange C, Heffner JE, Collins BS, et al: Pulmonary hemorrhage and air embolism complicating transbronchial biopsy in pulmonary amyloidosis. Chest 92:367–9, 1987. [PubMed: 3608608]

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