Christopher B. Weldon, MD, PhD, Robert C. Shamberger, MD › wp-content › uploads › 2013 › 07...

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Seminars in Pediatric Surgery (2008) 17, 17-29

ediatric pulmonary tumors: primary and metastatic

hristopher B. Weldon, MD, PhD, Robert C. Shamberger, MD

rom the Department of Pediatric Surgery, Harvard Medical School, Children’s Hospital Boston, Boston, Massachusetts.

Pediatric pulmonary tumors are rare. There is often a significant delay in diagnosis of pulmonary tumorssecondary to their rarity and nonspecific presenting physiologic and radiographic findings. A high indexof suspicion in pediatric patients with recurrent or persistent pulmonary symptoms is of paramountimportance in diagnosing pulmonary tumors at an early stage. Malignant pulmonary tumors are morefrequently diagnosed than benign lesions, with metastatic cancers being the most common. Completesurgical resection remains the basis of therapy for primary lesions, and its role in secondary cancers isbecoming more established. Adjuvant therapies are frequently employed depending on the precisetumor involved. Mortality rates vary greatly depending on tumor location, stage, and type.© 2008 Elsevier Inc. All rights reserved.

KEYWORDSPediatric;Lung;Tumor;Benign;Malignant;Review

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Primary pediatric lung neoplasms are rare entities. Sec-ndary cancers far outnumber primary tumors, and oneeport documents that 80% of all lung tumors, and over 95%f all malignant lung tumors, are metastatic disease fromonpulmonary cancers.1 However, the number of neoplasticesions pale in comparison to benign pulmonary diseaserocesses. Reports have documented a ratio of 1:5:60 forrimary cancers to metastatic lesions to benign diseasentities in the pediatric lung.2,3 Secondary lesions encom-ass diseases from most known pediatric cancers, includinghe adrenal gland, thyroid gland, gonads, liver, kidney, softissue, and bones.

Two comprehensive series to date (published a decadepart with the second building on the first)4,5 have attemptedo document the quantitative and qualitative aspects of theseesions by combing through institutional series and combin-ng these cases with others reported in the medical literatureesulting in data comprising over 383 patients. These seriesocument that the majority of primary lung tumors arealignant (65-76%) with an overall mortality rate of 30%.owever, benign pulmonary masses are not without signif-

Address reprint requests and correspondence: Christopher B. Wel-on, MD, PhD, Department of Pediatric Surgery, 300 Longwood Avenue,egan 3, Boston, MA 02115.

iE-mail: [email protected].

055-8586/$ -see front matter © 2008 Elsevier Inc. All rights reserved.oi:10.1053/j.sempedsurg.2007.10.004

cant mortality (8%) owing to the anatomic location ofany of these lesions and their propensity to invade into

urrounding structures in the mediastinum. Anatomically,rimary lesions arise from both the tracheobronchial treend pulmonary parenchyma proper, and they include a wideariety of histological subtypes: benign (inflammatory myo-broblastic tumors, 52%; hamartomas, 23%) and malignantbronchial adenoma, 40.5%; bronchogenic carcinoma, 16%;leuropulmonary blastoma, 15%).

Presenting symptoms can vary widely depending on theumor type, size, rate of proliferation, malignant potential,ascularity, and the location of the tumor within the respi-atory system. Symptoms for benign and malignant diseaserocesses differed.4,5 Benign lesions were asymptomatic inhe majority of cases (24%) owing to the fact that they areore often peripheral lesions. The most common symptoms

or benign lesions, when present at diagnosis, were fever14%), cough (12%), and pneumonitis (10.5%). For primaryalignant lesions, however, cough (35%), pneumonitis

23%), fever (18%), respiratory distress (12%), and hemop-ysis (11%) were the most common findings, and this cor-elates with the fact that the most common tumors, bron-hial adenomas, are predominantly endobronchial lesions.nly 6% of patients with malignant lesions were asymp-

omatic. There is often a delay in diagnosis of these lesions
n children due to the nonspecific nature of many of the

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18 Seminars in Pediatric Surgery, Vol 17, No 1, February 2008

ymptoms and their extreme rarity.1,6-9 Often, infectiousauses or reactive airway disease are the presumed diag-oses, and the patients are treated medically for severalonths or even years before diagnosis.1,5,7

Diagnostic studies initially consist of chest radiographs.indings on these studies are helpful but are not specific forny single entity, and include atelectasis, hyperinflation,nfiltrative processes, mass lesions, pleural or pericardialffusions, and hyperlucency. Many of these findings, asreviously mentioned, will be attributed to more commoniagnoses, such as reactive airway disease, foreign bodyspiration, or infectious processes. Obviously, a mass foundn a chest radiograph will prompt further imaging studies,ut this is not often appreciated, especially for small, cen-rally located lesions. Furthermore, combining the symp-oms of coughing and wheezing with hyperlucency on chestadiographic examination would likely be more suspiciousor a foreign body inhalation than a pulmonary tumor basedn the frequency of the two lesions. If suspicions andymptoms persist, computed tomography with three-dimen-ional reconstruction is the next modality employed. It isore sensitive (97%) than a chest radiograph in detectingasses, especially for central lesions.10,11 The specificity of

omputed tomography, however, is low for pulmonary le-ions, except for the pathognomonic “popcorn-like” calci-cations of hamartomas12 and the minority of carcinoid

umors that are calcified (26%).13,14 Magnetic resonancemaging for pulmonary hamartomas15 and carcinoid tu-

ors16,17 has been described, but it is not widely employed.urthermore, carcinoid tumors can also be diagnosed byunctional imaging techniques that rely on radiolabeled pep-ide analogues that react with specific somatostatin recep-ors found in increased number on carcinoid tumors with aigh degree of sensitivity and specificity.18,19 Although flu-rodeoxyglucose (FDG) positron emission tomography hashigh sensitivity and specificity in identifying increasedetabolic activity, and hence malignancy in solitary pul-onary nodules,20 carcinoid tumors are not avid.21 Further-ore, neither magnetic resonance nor functional imaging

tudies have gained widespread applicability or acceptabil-ty in the pediatric population in the evaluation and man-gement of pulmonary lesions.

Bronchoscopy, rigid or flexible, is useful in examiningatients with persistent symptoms and/or radiographicallyefined lesions, especially if centrally located.22,23 Althoughhe possibility exists for macroscopic inspection, pathologicampling, and therapeutic treatment of these lesions, onlyross inspection is readily recommended in treating pediat-ic lesions. Bronchoscopic biopsy can be employed as well,ut again only for endobronchial lesions, and the possibil-ties of indeterminate pathologic analysis from small sampleize and poor sample quality as well as the risk of hemor-hage with fatal outcome from this approach are signifi-ant.7,24,25 Therapeutic bronchoscopic resection and treat-ent using a combination of mechanical, thermal, radiation,

nd photobiologic therapies can be performed,26,27 but only t

or endobronchial lesions. Furthermore, the extent of theseumors is notoriously underestimated on bronchoscopy, andence, they are often referred to as the “tip of the iceberg”esions. Finally, this mode of treatment has not been uni-ersally accepted by the pediatric medical community and isnly recommended for small, benign lesions where com-lete excision is likely.2,5

Operative exploration with total gross and microscopicesection of all involved tissues is recommended for allypes of lesions, regardless of histologic subtype.2,4,5 Bothpen and minimally invasive techniques have been em-loyed in the resection of these lesions; however, the largernd more centrally located lesions that may require compli-ated sleeve resections or tracheobronchial reconstructionre more suitable for a formal thoracotomy. The goal of anyrocedure, however, should be the preservation of as muchormal parenchyma as possible. Caution must also be men-ioned in regard to pneumonectomy in an infant or younghild, for severe kyphoscoliosis may develop.28 Therefore,arenchymal-sparing resections are recommended, if possi-le. A proposed treatment algorithm for the management ofediatric lung lesions is shown in Figure 1.

enign lesions

nflammatory myofibroblastic tumor (IMT)

MT is a myofibroblastic spindle cell soft tissue tumor withnfiltrative plasma cells, lymphocytes, and eosinophils as de-ned by the World Health Organization (WHO)29 (Figure 2).t has been given many other names in the last half-centuryn the medical literature, the most well-recognized nameseing inflammatory pseudotumor and plasma cell granu-oma. It was first described in 1939 as a primary pulmonaryesion,30 and theory has held that it forms as a reaction to arevious tissue insult.31 Various antecedent infections haveeen described in many reports with rates varying from 5%o 37%.32-35 Furthermore, viral etiologies for these lesionsave also been proposed after molecular constructs of thepstein–Barr and Human Herpesvirus-8 viruses were recov-red from these lesions,36-40 but these theories are as yetnproven. Though traditionally considered benign, recentolecular analysis has cast doubt on this assumption. TheHO has defined this tumor as an intermediary lesion that

as been characterized by a molecular rearrangement onhromosome locus 2p23 involving the tyrosine kinase re-eptor anaplastic lymphoma kinase (ALK) involved in otherorms of malignancy.41 Although this genetic lesion haseen associated in some IMTs,42-44 it has not been uni-ormly documented in all lesions, and debate continues onhe true nature and malignant potential of this lesion.

It is the most common benign pediatric pulmonary lesionepresenting more than 50% of all documented benign le-ions.4,5 It is predominantly a peripheral lesion that has a
endency to grow slowly, but it can invade local structures

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19Weldon and Shamberger Pediatric Pulmonary Tumors

roducing a variety of symptoms in the pediatric popula-ion. Furthermore, multiple deaths have been documented asresult of local invasion by this tumor.4,33,45 It is far more

ikely to recur locally than metastasize, with reported fre-uency of 3% to 24%.46,47 The largest and most compre-ensive review demonstrated a 14% recurrence rate withulmonary IMTs.48 The presence of local invasion wasighly correlated with local recurrence; IMTs confined tohe lung at the time of resection recurred in 1.5%, whereashose with extension beyond the lung recurred in 46% ofases. This latter figure is important since 27% of patientsave locally invasive disease at the time of resection. Treat-ent should be complete surgical resection, including pos-

ible pneumonectomy. Fat-laden macrophages signify pos-tive margins on pathological analysis.4 Enucleation aspposed to resection resulted in the only cases of a recur-ence of an IMT localized to the lung.49 Adjuvant therapiesave employed both radiotherapy50 and chemotherapy (includ-ng nonsteroidal antiinflammatory drugs)51-53 with some sus-ained success, but no specific regimen has gained wide-

igure 1 This algorithm demonstrates the proposed evaluationndertaken as a first step, including a history and physical examinaA). The most likely underlying disease process should be treateollow-up within 2 to 4 weeks. If symptoms persist (B), then a repomogram (CT) and pulmonology consult (C). If this workup, incurther medical therapy should be administered with close follow-arranted (E). But if the symptoms persist (F), then a repeat wor

G). If this workup is again negative, then medical management sronchoscopy (J) demonstrate a lesion, then the workup should proesion is peripheral (K) on a CT scan and amenable to a biopsy (M)reatment (O). If the lesion is centrally located, then a broncisease-specific treatment (O).

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amartoma

amartomas are benign lesions that are described in manyrgans, but especially the lung and liver. First described in904 by Albrecht,54 it is a tumor primarily composed oformal cells ordered in an abnormal pattern. Pulmonaryamartomas are composed of cartilage and gland-like for-ations in an irregular and haphazard orientation. These

umors grow slowly.55,56 Macroscopically, they are de-cribed as well demarcated, but without a defined capsule,nd they are composed of lobules of glandular tissue witheep septa of connective tissue. The reported incidence inn autopsy series is 0.25%.57 Hamartomas represent 8% ofll pulmonary neoplasms in all ages,58 and it is the mostommon benign pulmonary lesion in adults, most com-only diagnosed in the fourth to seventh decades in

ife.55,59 However, this is not the case in pediatric patients,here it is the second most common benign pulmonary

esion (18-23%).4,5 Radiographically, hamartomas can havepathognomonic stippled, “popcorn” calcification on chest

atient with respiratory symptoms. A baseline workup should be/P), chest radiograph (CXR), and laboratory evaluations (LABS)the appropriate medical therapy, and then there should be closerkup should be performed with the addition of a chest computedthe chest CT and pulmonology consults, is nondiagnostic, then

. If the patient becomes asymptomatic, then no further therapy isould be ordered, including a bronchoscopy and another chest CTbe continued with close follow-up (H). If the chest CT (I) and/ors if these studies were positive from the first encounter (C). If the

this should be considered before resection (N) and disease-specificy should be performed (J), before resection (N) and further

of a ption (H

d witheat woludingup (D)kup shhouldceed a, thenhoscop

adiographs, but this finding is only present in 10% to 25%

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f cases.12,59 The vast majority are isolated tumors locatedn the periphery of the lung, and though described as asymp-omatic in adults, they are frequently symptomatic in chil-ren owing to their size and anatomic location.4 In fact, foureaths have been reported secondary to significant pulmo-ary compromise. Conservative surgical resection is recom-ended for treatment of these lesions. Finally, pulmonary

amartomas have been found in association with extra-drenal paraganglioma and gastric smooth muscle tumors indolescent females (the Carney triad),60 and if one of theseumors is discovered, a thorough attempt should be made toetermine whether the others tumors are present.

alignant lesions

ronchial adenoma

ronchial adenomas have been cohorted into a single entity,lthough they are really several distinct tumors. They are theargest group (40%) of malignant lung lesions in the pedi-tric population.4,5 The three most common tumors in thisroup are carcinoid tumor, mucoepidermoid carcinoma, anddenoid cystic carcinoma (cyclindroma) in decreasing orderf frequency.

Carcinoid tumors are the most common malignant pul-onary neoplasm in pediatric patients2,4,5,61 (Figure 3). An

nalysis of over 10,000 patients from the SEER database ofhe National Cancer Institute documented that bronchial orulmonary carcinoid tumors accounted for 28% all of car-inoid lesions diagnosed.62 The term “carcinoid” was firstsed by Obendorfer in 1907,63 whereas the term “carcinoidyndrome” was coined by Thorson in 195464 to describe the

igure 2 CT scan of an 18-year-old girl who presented witheft-sided chest pain. Scan revealed a mass causing collapse of theower lobe with some areas of calcification. Initial percutaneousiopsy was consistent with an inflammatory pseudotumor of theung. She subsequently underwent resection with a left pneumo-ectomy.

ssociated symptoms of flushing, palpitations, fainting, ab- a

ominal pain, diarrhea, bronchospasm, and endomyocardialalvular disease. These tumors arise from Kulchitsky cellsf the amine precursor uptake and decarboxylation (APUD)ystem that are found in many organs in the body, includinghe bronchi and lungs. These cells are involved in theynthesis and metabolism of tryptophan and other vasoac-ive amines, and the primary way to diagnose carcinoidumors is by urinary analysis for the primary degradationroduct of tryptophan metabolism (5-hydroxyindoleaceticcid, 5-HIAA). Molecular analysis has determined that p53utations and disordered expression of anti- and pro-apop-

otic member proteins of the Bcl-2 family may contribute tooth disease oncogenesis and aggression.65 Carcinoid tu-ors may occur in isolation, or infrequently (4%) as part of

he Multiple Endocrine Neoplasia syndromes (MEN I).66,67

hey may present infrequently with Cushing’s syndrome68

r carcinoid syndrome (1-7%).69,70 The carcinoid syndromen pulmonary tumors generally signifies extrapulmonaryetastatic disease (hepatic or regional and/or local lymph

odes). Carcinoid tumors are separated into two subsets,ypical (90%) and atypical (10%); the latter, defined byistopathological criteria suggestive of a more aggressivehenotype, includes the presence of necrosis or an elevateditotic index. However, regardless of this distinction, both

ariants may metastasize. Surgery is the mainstay of treat-ent; the goal is to remove all microscopic and macro-

copic disease, including associated lymph nodes. The-year survival rates for local, regional, and disseminatedisease are 81%, 77%, and 26%, respectively.62 Typicalarcinoid lesions have fewer lymph node metastases (5-0%71 versus 30-75%72) and a more favorable prognosisstage for stage) in comparison to atypical lesions. Finally,etastatic disease in adult patients, especially to liver, has

een treated with adjuvant radio- and chemotherapy, he-atic artery embolization, hepatic transplantation, and pri-ary and secondary metastasectomy in combination with

he administration of either short- or long-acting somatosta-in analogues for symptomatic control of carcinoid syn-rome. However, none of these modalities have been pro-osed in children, except for the medicinal control ofarcinoid syndrome.

Mucoepidermoid tumors are the second most commonesion in this cohort,4,5 and they represent about 10% of allulmonary tumors in pediatric patients.1 They originaterom mucous glands in the submucosa and respiratory mu-osa.73,74 They are centrally located and infrequently me-astasize to lymph nodes or distant sites. Histopathologi-ally, these tumors are divided into high- and low-gradeesions, with the overwhelming majority of lesions defineds low-grade in children.1,7-9,28 In fact, there have only beenhree high-grade lesions reported in children,28 and the onlyeath noted in this entire cohort was in this subset. Man-gement of mucoepidermoid tumors involves the completeesection of all gross and microscopic disease. High-gradeesions carry a dismal prognosis in the adult population with
ll patients being dead within 16 months in one series.75

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Adenoid cystic carcinomas are the least frequently iden-ified bronchial adenoma in children,4,5 and this tumor isescribed as being a salivary gland-type tumor. They arelow growing, submucosal masses with a high incidence ofocal recurrence and dissemination.72 The tumors tend torow radially into the pulmonary parenchyma as opposed tohe tracheobronchial tree.72 Hence, frozen section analysist the margin of resection is mandatory to determine com-leteness of resection in light of these insidious growthatterns. They also have a penchant to have perineural

igure 3 Lateral chest radiograph (A) of an 11-year-old boy wobe which was confirmed on the computed tomogram. (B) Subntermedius, presumed to be a carcinoid tumor which was confirmnline.)

pread and direct extension into local and regional lymph d

ode basins. Treatment is extirpation with negative surgicalargins and lymphadenectomy, but late recurrences up to

0 years have been described.76,77

ronchogenic carcinoma

he second most common malignant pulmonary cancer inhe pediatric population is bronchogenic carcinoma (16.8%)5

ith adenocarcinoma and undifferentiated carinomas ac-ounting for the majority of lesions4,5 (Figure 4). It was first

ented with intermittent cough. It revealed collapse of the middlet bronchoscopy (C) revealed a lesion obstructing the bronchus) on subsequent pathology. (Color version of figure is available

ho pressequened (D

escribed in 1876,78 and it is far more common in adults

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han in children. Certain bronchogenic carcinoma subtypes,quamous cell and bronchioloalvelor subtypes, are knowno arise from parenchymal cystic lesions in infants andhildren, including bronchogenic cysts and cystic adenoma-oid malformation.4,79,80 The incidence in children is 0.16%n the first decade of life, 0.9% in the second decade, andnly 1.2% in all people less than 40 years old.81,82 Thencidence peaks in the sixth to seventh decades of life.imilar to the adult population, surgical intervention is therimary mode of therapy with ipsilateral lymphadenectomyor localized disease.83 Adjuvant therapy for local diseasend disseminated disease at diagnosis combines both radio-nd chemotherapy and will vary depending on the specificistologic subtype and disease stage. Unfortunately, theseumors are generally metastatic at diagnosis, and the pa-ients often present with symptoms (bone pain, weightoss4,84,86) suggestive of this disease burden. The mortalityate mirrors that of the adult population with one large seriesocumenting those pediatric patients with disseminated dis-ase at diagnosis live less than 7 months.4 The recentlyescribed basaloid variant85 bronchioloalvelor subtype87

Figure 5) has a more favorable prognosis as described byhye and colleagues.88

Special consideration should be made for squamous cellariant (Figure 6) which account for 12% of describedesions,4,89 and unlike adults, environmental exposures, in-luding tobacco products, are not a known risk factor. How-ver, Human Papilloma Virus (HPV) has been postulated tounction as an inciting factor for the development of squa-ous cell carcinoma (SCC) as it has been found in meta-

lastic SCC pulmonary lesions90 and in tracheobronchialesions91,92 from squamous papillomas or papillomatosis,ut there is not convincing evidence to make a definitivetiologic link.93 Regardless of this debate, HPV 6 has beenound in benign lesions, and HPV 11, 16, and 18 have been

igure 4 An 8-year-old boy presented with a persistent coughnd tachypnea. Chest radiograph shows mediastinal widening andhe CT scan with IV contrast showed an extensive central lesionhich can be seen compressing the pulmonary artery to the left

ung. Biopsy revealed bronchogenic carcinoma.

ound in both the malignant transformation of juvenile- c

nset respiratory papillomatosis and carcinomas found insolated papillomas.94-96

leuropulmonary blastoma (PBB)

BB is the third most frequent (15.5%) pediatric primaryulmonary cancer as previously described in the seminaleries on this topic4,5 (Figure 7). The lesion was first char-cterized in 1945,97 revised in 1953,98 modified by Spencern 1961,99 and finally defined by Manivel in 1988100 whooined the term pleuropulmonary blastoma to anatomi-ally and histologically define this lesion and distinguisht from a similar cancer commonly seen in adults. It isomprised of mesenchymal elements and embryonictroma without a neoplastic epithelial component and ishought to arise from somatopleural mesoderm or thoracic

igure 5 Chest radiograph (A) showing the extensive nature ofhe disease, and CT scan (B) showing multiple lesions with theharacteristic cavitary centers of a patient with bronchial alveolar
arcinoma.

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planchnopleura.101,102 Hence, it has pulmonary, pleural,nd mediastinal lineages. These lesions have been micro-copically and macroscopically categorized by Dehner ac-ording to the proportion of cystic and solid componentsithin the lesion (Type I, only cystic components; Type II,

ystic and solid components; Type III, solid compo-ents).103 Regardless of the histological evaluation, therognosis is poor with mortality rates ranging from 60% to5% at 5 years4,104-107 and only 8% at 10 years.101 Negativerognostic factors are size �5 cm, metastatic diseases, andositive thoracic lymph nodes.108-112 Treatment consists ofurgical resection for locally confined lesions with adjuvanthemotherapy postoperatively, or in the presence of meta-tatic disease at diagnosis, neoadjuvant chemotherapy, andadiotherapy.113 For those patients with recurrent or residualisease, chemotherapy and radiotherapy are also recom-ended as described by several groups.113,114 Finally, similar

o bronchogenic carcinoma, these lesions have been noted torise from congenital anomalies of the lung, including cys-ic adenomatoid malformation, sequestrations, and broncho-enic cysts.115-118 Weinblatt first described this relationshipn 1982,115 and Tagge and colleagues later documented that1% arise from cystic pulmonary lesions.117

etastatic tumors

etastatic pulmonary tumors are more frequently encoun-ered in the pediatric population than primary lesions. Kay-on has recently published an excellent review of the utilityf pulmonary metastasectomy in children,119 but there is aack of tumor-specific, prospective, randomized clinical tri-ls critically evaluating this therapeutic intervention in theediatric population. The data that do exist are generallyetrospective small studies that span many years and treat-

igure 6 CT scan of an 18-year-old boy who had suffered fromespiratory papillomatosis for many years. He ultimately devel-ped squamous cell carcinoma of the lung related to the papillomairus. This scan shows the extensive and invasive nature of hisdvanced disease.

ent regimens, and they can only serve as a guide to s

etermining when metastasectomy is appropriate. Beforettempting metastasectomy, however, four criteria shoulde met: (1) primary tumor diagnosis; (2) primary tumorocal control; (3) effective adjuvant treatment modalities;nd (4) removal of all evident disease.

drenocortical carcinoma

ulmonary metastasectomy for adrenocortical carcinomahould be considered since effective adjuvant therapies areot available. A recent review of the International Pediatricdrenocortical Tumor Registry revealed that the 5-year,

vent-free survival was 54%, and the incidence of pulmo-ary metastases was 7% at presentation.120 Prognosis wasmproved for younger patients with completely resected,mall, early-stage tumors with virilizing symptoms, but sep-rate analysis of the patients with lung metastases could note performed because of the small number of cases. How-ver, reports in the literature document long-term survival inatients (predominantly adults) who underwent pulmonaryetastasectomy for adrenocortical carcinoma.121,122 In fact,wauk and colleagues documented that complete surgical

xcision of all metastatic disease provided for a 5-yearurvival of 71% versus 0% for those with unresected dis-ase.123 Furthermore, Schulick and colleagues echoed theseesults and sentiments and advocated for repeat metastasec-omies.124 They reported that, for every reoperation, the

edian survival was longer for the complete versus incom-lete resection cohort, which may be a function of theiology of the tumor involved as opposed to the operationerformed.

ifferentiated thyroid cancer

ulmonary metastasectomy should only be performed inifferentiated thyroid cancer where there is indecision abouthe nature of a pulmonary lesion, especially after treatment.isseminated pulmonary disease is found in up to 25% ofatients,125-131 but it does not confer a dismal prognosisith survival rates of greater than 94% reported.125-131 A

omprehensive review on the treatment of thyroid cancer inhildren has recently been published.131 Of the 740 casesocumented, 131 (17.7%) had evidence of pulmonary dis-ase, and they were treated with radioactive iodine. The 5-nd 10-year survival rates were 99.5% and 98.8%, respec-ively, with only 5 children dying of distant metastases with

mean follow-up of 115 months. With therapeutic radio-ctive iodine administration for pulmonary metastases,8.9% had a complete response (negative nuclear imagingnd thyroglobulin level �1 ng/mL), 47.7% had a partial buttable response (negative nuclear imaging and thyroglobulinevel 1-10 ng/mL), and 23.4% had a partial response.

erm cell tumors (gonadal)

ulmonary metastasectomy for germ cell tumors (gonadal)
hould be considered, especially if present after adjuvant

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herapy is completed to determine the presence or absencef viable tumor within the lesion and the need for furtherdjuvant therapy. Germ cell tumors are chemosensitive le-ions with a long-term survival rate of 90%.132 However,esidual radiographic lesions after adjuvant therapies mayarbor viable tumor,132-136 with the lung being the mostrequent site of distant metastasis.133 Several groups132-136

ave examined their data concerning the role and utility ofulmonary metastasectomy in these patients, and the resultsemonstrate that over 40% of patients harbored viable tu-or cells within radiographically visible lesions post-

igure 7 (A) Chest radiograph of a 3.5-year-old boy who presef most of the right hemithorax. (B) CT scan showed a multi-lobuiopsy did not establish the diagnosis of pulmonary blastoma, butf multimodal chemotherapy showed a remarkable regression of tithin the lung. He subsequently underwent a right upper and mi

herapy. Therefore, the role of pulmonary metastasectomy is t

rimarily to define the presence of viable tumor in lesionsfter chemotherapy and for determining further treatmentegimens.

epatoblastoma

ulmonary metastasectomy for hepatoblastoma should onlye performed for radiographically persistent lesions afterdjuvant therapy. Data to support this concept have beenublished by Feusner and colleagues137 representing thehildren’s Cancer Group and two reports from the Interna-

ith a cough and some dyspnea on exertion showed opacificationesion in the lung with cystic and solid components. Percutaneousen wedge biopsy did. (C) Chest radiograph following four cyclesor, although the MRI scan (D) showed significant residual tumorbectomy and completion of his chemotherapy.

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umors.138,139 Feusner and colleagues137 reported on sixatients with pulmonary recurrence who were treated me-astasectomy and chemotherapy with four patients having aomplete remission; three had a survival of greater than 5ears. Perilongo and colleagues138 documented the resultsf SIOPEL1, where 20% of patients with hepatoblastomaresented with pulmonary metastases, and the 5-year event-ree survival was 28%. A sustained remission from chemo-herapy alone in these patients was achieved in only6%. Schnater and colleagues139 analyzing the same non-andomized data emphasized that only 41% of patients whoresented with pulmonary metastases were long-term sur-ivors, but all patients who underwent surgery and chemo-herapy to treat their pulmonary metastases were alive atata analysis.

euroblastoma

ulmonary metastasectomy for neuroblastoma should note performed. However, if there is concern about the naturef a pulmonary lesion after or during treatment, then ithould be biopsied. The incidence of pulmonary metastasesrom neuroblastoma has been reported from �1% to3%140-144; however, most large studies report rates of 5%r less.142-144 These patients with pulmonary metastasesrom neuroblastoma have a poor prognosis, a higher asso-iation of unfavorable Shimada histology, MYCN amplifi-ation, and a lower event-free survival.143-144 Hence, thetility of performing resections except to confirm the diag-osis are not warranted.

ephroblastoma

ulmonary metastasectomy for nephroblastoma should note resected, and suspected lesions should only be biopsied.ome authors145,146 have advocated for primary pulmonaryetastasectomy to spare the effects of radiotherapy147 on

atients, but other reports have demonstrated the efficacy ofhemotherapy and radiotherapy in the treatment of pulmo-ary metastases over chemotherapy and surgical excision,egardless of pathological subtype or stage.148-150 Themportance of biopsy for suspicious pulmonary lesions,specially if small (�1 cm) and found only on computedomography was confirmed recently by Ehrlich and col-eagues.151 Thirty-three percent of those who received ra-iotherapy had a biopsy that was negative for tumor, andence they were overtreated.

steosarcoma

ulmonary metastasectomy for osteosarcoma should be per-ormed. In 1971, a significant survival advantage for this mo-ality was reported over standard chemotherapy alone.152

any reports in the literature have documented the utilitynd success of this approach as well.153-171 Furthermore, the
riteria for pulmonary metastasectomy require: (1) a multi-
odality approach that addresses synchronous pulmonaryesions at the time of local control; (2) repeated resectionsor metachronous lesions; (3) operative evaluation of sus-ected masses since computed tomographic imaging doesot identify all pulmonary lesions; (4) continued screeningor pulmonary lesions after the first occurrence as a majorityf patients will have at least one more pulmonary recurrenceithin 12 months of the first resection; and (5) the under-

tanding that other criteria—disease free interval and per-entage of tumor necrosis on histopathological evalua-ion—in addition to tumor burden are important prognosticactors.

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