Tumores Solitarios Pulmonares Inusuales

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Rare Solitary Benign Tumors of the LungJames S. Allan

Benign solitary neoplasms of the lung are relatively uncommon but nonetheless must be considered in

the differential diagnosis of any solitary pulmonary lesion. Ironically, the advent of improved tomo-graphic imaging and its increasingly broad clinical application have led to a greater recognition of

benign solitary pulmonary lesions, presenting the surgeon with a complex management dilemma.

Most benign lesions are relatively bland radiographically, making their differentiation from carcinoma

difficult. Often, diagnostic certainty can only be achieved with complete resection. Fortunately, ad-

vances in minimally invasive thoracic surgery make this prospect less daunting for the patient and

surgeon. This article reviews a subset of solitary lesions categorized as rare benign neoplasms from

histologic, radiographic, and clinical points of view.

2003 Elsevier Inc. All rights reserved.

Key words: Lung, neoplasm, tumor, benign, solitary.

The seemingly straightforward presentationof a patient with a small, asymptomatic sol-itary lung nodule raises one of the more difficult

clinical situations that a thoracic surgeon is likely

to encounter. In this scenario, it is incumbent

upon the surgeon not only to exclude malignancy

with a high degree of certainty but also to do so

with a minimum of intervention. Moreover, most

patients facing this situation expect a surgeon to

provide them with a clear diagnosis, but few are

prepared at the outset to undergo a potentially

morbid operation simply to rule out a malig-nancy. This conundrum is further intensified

when the lesion is radiographically bland, when

the patient has a slightly increased risk for lung

cancer, and when comorbidities are present that

would make operative intervention less desirable.

This article reviews a group of rare pulmonary

neoplasms that typically present as solitary le-

sions. For the most part, these lesions are asymp-

tomatic and radiographically indistinct from

many common neoplasms. Because of these

traits, the majority of these diagnoses are only

obtained after excisional biopsy, which is typicallycurative. Notably excluded from this review are

the more common benign pulmonary lesions, in-cluding hamartomas, benign fibrous tumors ofthe pleura, granulomas, and other inflammatorynodules, all of which are considered elsewhere.

Historical Notes

The first major series addressing the issue of theasymptomatic solitary pulmonary nodule waspublished in 1963 by Steele.1 Steele compiledhistologic data from 882 male patients who un-

derwent pulmonary resection. In this study, hefound that 36% of the resected lesions were ma-lignant, while 64% were benign. Granulomas rep-

resented the overwhelming majority of the be-nign lesions. The relatively high incidence ofbenign granulomas (often tuberculous in etiol-ogy) in this series is both a reflection of thepatient population and the era in which the study

was conducted. Also, this study was performedbefore the advent of computerized tomography(CT), and therefore, it only included asymptom-atic lesions that were large enough to be seen on

plain chest radiography. If Steeles data set is

limited just to true benign solitary neoplasms ofthe lung and tracheobronchial tree (excludingbenign fibrous tumors of the pleura), these be-nign neoplasms constitute approximately 10% ofthe resected neoplasms. Moreover, 94% of theseneoplasms were found within the lung paren-chyma, with only 6% occurring endobronchially.

In a later series from the Mayo Clinic, Arri-

goni and colleagues described the relative fre-quencies of some of the more common, benign

From the Division of Thoracic Surgery, Department of Surgery,

Massachusetts General Hospital, and the Harvard Medical School,

Boston, MA.

Address reprint requests to James S. Allan, MD, Massachusetts

General Hospital, Blake 1570, 55 Fruit Street Boston, MA 02114.

2003 Elsevier Inc. All rights reserved.

1043-0679/03/1503-$30.00/0

doi:10.1016/S1043-0679(03)

315Seminars in Thoracic and Cardiovascular Surgery, Vol 15, No 3 ( July), 2003: pp 315-322


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lung neoplasms.2 These data are described inTable 1. As seen, the pulmonary hamartoma isthe most commonly encountered benign solitarypulmonary neoplasm, accounting for over three-fourths of the benign neoplasms resected. Thenext most common neoplasm reported by Arri-goni et al is the benign mesothelioma, which isnow more commonly called a benign fibrous tu-mor of the pleura.2 Once these 2 lesions areexcluded, only a handful of rare tumors remain.

Although there is no recent autopsy series or casestudy that adequately addresses this issue, it islikely that the apparent prevalence of rare benigntumors will grow as the use of high-resolution CTincreases.

Classification of Benign Lung Tumors

Liebow made the first attempt at classification ofbenign lung tumors at Yale University,3 and amodification of Liebows original nosology wasadopted by the World Health Organization (Ta-ble 2). This classification schema was based pri-marily on the presumed cell of origin of the neo-plasm and has evolved to take advantage of ourbetter understanding of cell ultrastructure withthe use of electron microscopy. Also, over the

years, several neoplasms originally thought to be

benign are now properly recognized as low-grademalignancies and have been reclassified (eg,

bronchial adenomas, pulmonary blastoma, tumor-lets, hemangiopericytomas, and mucosa-associatedlymphoid tumors).

Benign Solitary Neoplasms of EpithelialOrigin

Papillomas of the Tracheobronchial Tree

Papillomas of the tracheobronchial tree are be-

nign neoplasms of the squamous epithelium.

They have been subclassified as (1) solitary be-nign papillomas; (2) multiple benign papillomas;(3) benign combined bronchial mucous gland andsurface papillary tumors; and (4) bronchial pap-illomas. In addition, there is a fifth variant, which

is in fact malignant, known as the papillary bron-chial carcinoma in situ. This subsection will beconfined primarily to the solitary benign papil-loma.

Most commonly, solitary papillomas are seenin the proximal airway. In the pediatric popula-tion, these lesions often present in the larynx,

while in the adult population, these lesions typi-cally originate in the upper trachea. Only ahandful of cases have been seen distal to the

carina, and these bronchial papillomas have ahigh association with subsequent bronchial carci-noma.4 Also, the solitary papilloma appears to bemore common in the adult male population,

while children tend to present with multiple pap-illomatous lesions.5

Histologically, the more proximal benign pap-illomas tend to be pedunculated with a thin cen-tral fibrovascular core covered by a stratified

squamous epithelium. The more distal lesions

Table 2. Classification of Benign Lung Tumors

Epithelial neoplasms

PapillomasBenign inflammatory polyps

Mesodermal NeoplasmsVascular

HemangiomasLymphangiomas

BronchialFibromasChondromasLipomasGranular cell tumorsSclerosing hemangiomasLeiomyomas

Neurogenic tumorsNeuromas

NeurofibromasNeurilemomas

Primary pulmonary meningiomasTumors of developmental or unknown origin

TeratomasChemodectomasClear cell tumorsIntrapulmonary thymomas

Inflammatory lesions and pseudotumorsInflammatory pseudotumorsNodular amyloid

Table 1. Relative Frequencies of Benign LungNeoplasms2

Hamartoma 100Benign fibrous mesothelioma 16Inflammatory pseudotumor 7Lipoma 2Leiomyoma 2Hemangioma 1

Adenoma 1Mixed tumor 1Total 130

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are typically lined with a mixed epithelium, in-cluding glandular elements. It is believed thatsolitary benign papillomas result from a viralinfection with human papilloma virus types 6 and116 and that there is a small potential for malig-

nant degeneration.The most common presenting symptom of a

patient with a solitary papilloma is cough. Inaddition, patients may present with hemoptysis,

wheezing, or recurrent pneumonia. Unless bron-chial obstruction has occurred, the chest radio-graph is typically normal. Lesions may be identi-fied on CT or plain-film tomography of thetrachea.

The diagnosis is readily made on bronchos-

copy. Likewise, treatment typically consists ofbronchoscopic resection using either conven-tional rigid bronchoscopic techniques or laser ab-lation. On a rare occasion, pulmonary resectionmay be necessary for a distal papilloma.

Benign Inflammatory Polyps

Benign inflammatory polyps (sometimes termedfibrous polyps) of the tracheobronchial tree arerelatively uncommon and are difficult to differ-entiate from papillomas. Like tracheobronchialpapillomas, benign inflammatory polyps have apredilection for the upper respiratory tract. How-ever, they tend to be covered by an epitheliumthat shows columnar differentiation as well asgranulation tissue. Like solitary papillomas,

these polyps tend to present with a history ofchronic cough and occasional hemoptysis. Signsand symptoms of distal airway obstruction arequite rare. Again, bronchoscopic removal is gen-erally successful.7

Benign Solitary Neoplasms ofMesodermal Origin

Hemangiomas

The pulmonary hemangioma is a benign vasculartumor that can be found throughout the respira-tory tract. Most commonly, this lesion is seen inthe wall of the trachea or a mainstem bronchus.However, it can also be found in the pulmonaryparenchyma, usually in a subpleural location. Ap-proximately two-thirds of pulmonary hemangio-mas are solitary. When multiple lesions are

present, one must suspect the generalized disor-

der of hereditary telangiectasia (Osler-Weber-Rendu disease).

The pulmonary hemangioma is a true neo-plasm consisting of a cluster of thin-walled ves-sels with little supporting stroma. The term cav-

ernous hemangioma is sometimes used to referto a hemangioma that has a cystic central com-ponent, often filled with a serosanguineous fluid.The term sclerosing hemangioma is a misno-mer and will be considered later in this article.

When found in the central airway, the heman-gioma is readily identified on bronchoscopy and isseldom obstructing. Some investigators have rec-ommended Nd:YAG laser ablation due to its pro-pensity to bleed with classic bronchoscopic resec-

tion techniques.8 Hemangiomas are also knownto regress with focal radiation therapy, if surgicalablation is not practical.

When located in the pulmonary parenchyma,the solitary hemangioma tends to be a sharplycircumscribed rounded lesion with strong con-trast enhancement on CT. This result gives thehemangioma a radiographic appearance that isquite similar to that of some contrast-enhancing

malignant lesions, such as carcinoid. A conserva-tive wedge resection is the preferred treatment ofparenchymal hemangioma.

An important distinction must be made be-tween the true hemangioma and arteriovenousmalformations (AVM). AVM are not true neo-

plasms but rather are congenital vascular anom-alies.9 Pulmonary AVM are generally asymptom-atic solitary nodules typically found in the lower

lobes. Contrast-enhanced CT will typically showa vessel providing arterial inflow and another

vessel providing venous drainage. Because thevascular inflow is typically derived from the pul-monary circulation, a large, pulmonary AVM maybe associated with significant right-to-left shunt-ing, creating clinical signs such as cyanosis, club-bing, and polycythemia.9 Like true hemangiomas,there is an association between multiple pulmo-

nary AVM and hereditary telangiectasia.

Lymphangiomas

The lymphangioma is a relatively uncommon tho-racic neoplasm that typically presents in the me-diastinum or in the trachea of an infant orchild.9,10 Only rarely does a lymphangiomapresent as a solitary pulmonary nodule. Contro-

versy exists in the literature regarding the demo-

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graphics of the patient population that can be

affected by this lesion. Shafer et al have reportedthe presence of thoracic lymphangiomas in pa-

tients ranging in age from 6 months to 67 years,

with a slight female predominance.11 In contrast,

Wilson and colleagues have found a strong malepredominance when only parenchymal lesions

were surveyed.12

Histologically, the lymphangioma is a benigncollection of proliferative, intercommunicating

lymphatic vessels that lack systemic lymphatic

communication. Cystic and cavernous featurescan sometimes be seen. It is most commonly

found in the neck, where it referred to as a cystic

hygroma. This benign lesion appears to be con-

genitally acquired and is hypothesized to repre-sent the simplest extreme of a spectrum of

lymphatic disorders that share a common patho-genesis, including lymphangiomatosis, lypmhan-giectasis, and the syndrome of lymphangiomyo-

matosis.

Although tracheal lesions in the pediatric pop-ulation can result in pneumothorax and respira-

tory distress, the solitary parenchymal nodule is

generally asymptomatic, although hemoptysishas been reported.13 Radiographically, these le-

sions typically appear as a smooth cystic mass,

although spiculation has been described occa-sionally.12 Wedge resection of solitary pulmonary

lesions appears to be curative.

Fibromas

Pulmonary fibromas are benign lesions arising atany level from the walls of the tracheobronchial

tree. Fibromas typically account for less than 1/10

of 1% of all resected pulmonary tumors. How-ever, despite its rarity, the benign fibroma is the

most common of the mesenchymal benign tu-

mors.14 Histologically, these lesions are made ofbenign-appearing spindle cells with an abun-

dance of collagen. Occasionally, these lesionsmay have a more myxomatous appearance.

Peripheral fibromas are typically asymptom-

atic, while those occurring in the more proximalbronchi can present with symptoms of respiratory

tract obstruction.15 Because these tumors are rel-

atively avascular, airway lesions are easily treatedwith bronchoscopic resection, and peripheral le-

sions can be excised with parenchymal-sparing

techniques.

Chondromas

Chondromas (and the related osteochondromas)are the second most common benign pulmonarytumors of mesenchymal origin.14 They are typi-cally found in association with the cartilaginous

wall of a large bronchus. Histologically, they aredistinct from endobronchial hamartomas in thatthey lack the other tissue elements that are typ-ically found in a hamartoma. These lesions aregenerally asymptomatic unless they become ob-structing. The treatment of these lesions is sim-ilar to that described for benign fibromas.

Lipomas

The lipoma is perhaps the rarest of the benignlung neoplasms, and most thoracic surgeons willnever encounter this lesion. However, the pulmo-nary lipoma was ironically one of the first lunglesions ever reported in the medical literature byRokitansky in 1854.16 These lesions typically oc-cur in middle-aged males and are slow growing.They arise endobronchially and can either be in a

central or peripheral location. Treatment is gen-erally accomplished by either endoscopic resec-tion or parenchymal wedge resection, as appro-priate.17,18

Granular Cell Tumors

Granular cell tumors (granular cell myoblasto-mas) are benign neoplasms composed of large

ovoid or polygonal cells that take up periodicacid-Schiff stain. Originally thought to be derivedfrom skeletal muscle tissue, they are now be-lieved to be of Schwann cell origin. Deavers andcolleagues reviewed a series of 20 patients, rang-ing in age from 20 to 57 years, with granular celltumors.19 There was no sex predilection for thistumor. Also, in approximately half the cases, thetumors were asymptomatic and incidentally dis-

covered. Most of these lesions were solitary andwere typically found adjacent to a large bronchus.

A parenchymal sparing pulmonary resection isthe treatment of choice. However, the surgeonmust be attentive to achieving complete resec-tion because the recurrence rate for this lesion ishigh in the absence of complete excision.20

Sclerosing Hemangioma

As mentioned previously, the sclerosing heman-

gioma is a bit of a misnomer. This lesion was first

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reported by Liebow and Hubbell in 1974 and hasbeen the subject of some controversy in the fieldof pulmonary pathology.21 In particular, some pa-thologists, on the basis of immunohistochemicalstudies, have asserted that the sclerosing heman-

gioma may occur from the type 2 alveolar pneu-mocyte rather than a vascular mesenchymalcell.22,23

Sclerosing hemangiomas typically present aswell-defined rounded masses arising in the pe-riphery of the lung. They most commonly occurin the lower lung fields of middle-aged women.Occasionally, partial calcification may be seen. Ina recent series, this neoplasm was identified inapproximately 1% of 919 patients who underwent

pulmonary resection over a 17-year period, mak-ing this lesion second in prevalence to pulmonaryhamartomas.22 Sclerosing hemangiomas are eas-ily shelled-out at operation, and there have beenno reports of recurrence following parenchymal-sparing resection of this lesion.

Leiomyomas

Leiomyomas are an uncommon benign tumor ofmesodermal origin, although the exact incidenceis difficult to determine. Originally, leiomyomas

were thought to be the fourth most commonbenign mesodermal tumor of the lung.14 How-

ever, more recent series suggest that this lesion

may be more common.24

The majority of theselesions present as incidentally found, asymptom-atic peripheral solitary pulmonary nodules. Ap-proximately two-thirds of patients who are af-fected are female.25

It is hypothesized that pulmonary leiomyomasoriginate from the smooth muscle present ineither the bronchial walls or the bronchial arter-

ies. The histologic appearance is quite similar toleiomyoma found elsewhere in the body. The sol-itary leiomyoma of the lung should not be con-fused with a clinically distinct entity known asbenign metastasizing leiomyomas, which some

believe to be of uterine origin, traveling to thelung via a hematogenous route. Because mostsolitary leiomyomas are asymptomatic, parenchy-mal-sparing wedge resection is usually sufficient

therapy.

Neurogenic Tumors

Neurogenic tumors occur with high frequency in

the posterior mediastinum. However, they are

quite uncommon in the parenchyma of the lungitself.26 The thoracic literature contains scantreports of benign neurogenic tumors occurringcentrally and peripherally within the tracheo-bronchial tree. These tumors have included

neuromas, neurofibromas, and neurilemomas(schwannomas). Like most other benign tumorsof the lung, symptomology depends on the loca-tion of the lesion. Therapy is either conservativeparenchymal resection or endoscopic removal/ablation, as appropriate.27,28

Primary Pulmonary Meningiomas

Meningiomas presenting in the pulmonary pa-renchyma are often metastatic from an intra-cranial source. Nonetheless, there have beenscattered reports of primary pulmonary meningi-omas, which typically present in older women.These lesions are usually well-circumscribed nod-ules and have been reported to be as large as 6cm. The treatment of pulmonary meningiomasconsists of conservative surgical excision, and

the prognosis is excellent.29,30 Nonetheless, thefinding of a meningioma in the lung mandatescareful evaluation to exclude an intracraniallesion.31

Tumors of Unknown or Developmental

OriginTeratomas

Teratomas are common anterior mediastinalmasses. However, they occur only rarely as aprimary lung lesion. It is difficult to determine

the exact frequency of pulmonary teratoma be-cause many investigators may have erroneouslyreported mediastinal teratomas extending intothe lung as primary pulmonary lesions.32 Terato-mas have the characteristic histologic feature ofcontaining tissue derived from all 3 germ celllayers. Calcification and sebaceous matter are

not uncommonly identified in these tumors. Themajority of pulmonary teratomas have been

found in the anterior segment of the leftupper lobe, and resection has proven to becurative.

Chemodectoma

Tanimura and colleagues have reported a total of

24 cases of primary pulmonary paraganglioma



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(chemodectoma) extant in the literature.33 For

the most part, these lesions tend to be solitary

and can grow to be quite large.34 When small,

these neoplasms are typically asymptomatic.

However, compressive symptoms can develop in

patients as these tumors grow. Again, conserva-tive pulmonary resection is considered curative.

One should also recognize that the solitary che-

modectoma is distinct from a related pathologic

condition of multiple small tumors, known as

minute chemodectoma tumors, described by

Torikata and Mukai.35

Clear Cell Tumors of the Lung

A total of approximately 35 clear cell tumors of

the lung have been reported in the world litera-

ture.36-38 Most of these patients were in their fifth

or sixth decades of life and presented with asymp-

tomatic, peripheral solitary pulmonary nodules.

There was no sex predilection among these pa-

tients, and these tumors were reported to shell-

out easily from the surrounding parenchyma.

There is a single report of the malignant degen-

eration of a clear cell tumor in a patient who

ultimately died of metastatic disease.39 Histolog-

ically, the clear cell neoplasm consists of cells

with abundant cytoplasmic glycogen with inter-

spersed neurosecretory granules, suggesting that

this unusual tumor may originate from Kul-chitsky cells. This tumor has also been given the

eponym sugar tumor of the lung.

Intrapulmonary Thymomas

Thymomas are common tumors of the anterior

mediastinum. However, ectopic thymic rests exist

in both the lung hila and the peripheral paren-

chyma.40 Occasionally, these ectopic thymic rests

will become thymomatous. The optimal treatment

for these rare intrapulmonary thymomas has notbeen defined. However, a recent histopathological

examination of one such case suggests that these

lesions can spread through the normal lymphatic

drainage of the lung. Therefore, treatment strate-

gies analogous to that of lung cancer, including

formal lobectomy and lymph node dissection,

have been advocated.41 These tumors are also

known to be radiation-sensitive if surgical resec-

tion is not possible.

Inflammatory Lesions andPseudotumors

Inflammatory Pseudotumors

The term inflammatory pseudotumor includes a

fairly wide histologic spectrum of diseases thathave been variably termed plasma cell granu-loma, histiocytoma, xanthoma, xanthofibroma,xanthogranuloma, and mast cell granuloma. Var-

ious attempts have been made to subclassifythese pseudotumors based on their histology.However, the rarity of these lesions makes thiseffort difficult.42,43 In general, these benign tu-mors are composed of a mixture of plasma cells,lymphocytes, and varying quantities of fibroustissue. They are typically found as solitary pul-monary nodules presenting in children younger

than 16 years of age. There is a slight femalepredominance.44 Although corticosteroids45 andradiation therapy46 have been used to treat thoselesions that could not be completely resected,conservative surgical excision is generally suf-ficient therapy. The pseudolymphoma is notconsidered here because it is now generally re-garded as a low-grade, mucosa-associated lym-phoid tumor.

Nodular Amyloid

Primary amyloidosis of the lung can present as alocalized solitary parenchymal lesion or as asessile endobronchial tumor near the orifices ofsegmental bronchi.1 These parenchymal tumorsare commonly identified at thoracotomy for asuspected malignancy, and treatment with con-servative surgical resection is generally adequate.The endobronchial lesion can be addressed byendoscopic resection or laser ablation.

Conclusions

In the United States, approximately 150,000 newsolitary pulmonary nodules (defined as lesionsless than 3 cm in diameter) are identified each

year.47,48 The incidence of malignancy amongthese nodules is quite variable, ranging from 10%to 70% in published series.49-55 Therefore, it isimportant for the surgeon to be thoroughly fa-miliar with the differential diagnosis of the soli-tary pulmonary nodule and to develop strategies

for diagnosis that do not rely on excisional biopsy.

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The rare benign tumors described here collec-tively account for less than 1% of all solitarypulmonary nodules, with hamartomas, granulo-mas, and other inflammatory lesions comprisingthe remainder of the benign lesions. Hamarto-mas and granulomas often have characteristicradiographic features, particularly regarding spe-cific patterns of calcification or fat inclusion.56

These specific findings may correctly prompt the

surgeon to pursue a nonoperative approach in themanagement of these lesions. Unfortunately, theless common benign lung neoplasms reviewedhere all tend to be radiographically bland and

will most likely be identified in the course ofa resection undertaken to rule out malignant

disease.Fluorodeoxyglucose-positron emission tomog-

raphy (FDG-PET) is the one current modality

that holds the promise of limiting the need forsurgical excision of solitary nodules of unknowncharacter. Presently, FDG-PET is extremely sen-sitive and has a strong negative predictive value

when applied to nodules more than 1 cm in di-ameter. The utility of PET in determining a careplan is greatest when the PET data are incorpo-rated into a Bayesian risk analysis model thatassesses the risk of malignant disease for a given

patient. Table 3 lists a series of likelihood ratiosfor malignancy derived from one particular caseseries, considering a variety of clinical and radio-graphic characteristics, including PET avidity.57

Although Bayesian analysis is imperfect in itsapplication (largely because most risk factors arenot statistically independent), this approach be-gins to quantify and standardize the risk-benefitanalyses that clinicians have performed subjec-

tively for many years.

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Table 3. Malignancy Likelihood Ratios for Various Clinical and Radiographic Characteristics57

Characteristic Likelihood Ratio Characteristic Likelihood Ratio

Age 60-69 yrs. 2.64 Lobulated mass 0.74Nonsmoker 0.15 Spiculated mass 5.5430 Pack/yr. 0.74 Malignant growth rate 3.40

30-39 Pack/yr. 2.00 Not calcified 2.2040 Pack/yr. 3.70 Benign calcification 0.01Hemoptysis 5.08 CT enhancement 15 HU 0.04Previous malignancy 4.95 CT enhancement 15 HU 2.320-1.0 cm 0.52 PET SUR* 2.5 0.061.1-2.0 cm 0.74 PET SUR 2.5 7.102.1-3.0 cm 3.67 PET-positive 4.303.0 cm 5.23 PET-negative 0.04

Abbreviations: SUR, standardized uptake ratio.



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322 James S. Allan

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