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Respiratory Medicine (2006) 100, 1174–1179

0954-6111/$ - sdoi:10.1016/j.r

�CorrespondE-mail addr

Survival of biphasic pulmonary blastoma

Serife Tuba Limana,�, Tamer Altinokb, Salih Topcua, AbdullahIrfan Tastepeb, Ali Uzarc, Sedat Demircand, Funda Demirage

aThoracic Surgery Department, The Faculty of Medicine, Kocaeli University, Kocaeli, TurkeybThoracic Surgery Department, Ataturk Chest Disease and Thoracic Surgery Center, Ankara, TurkeycThoracic Surgery Department, Alanya State Hospital, Antalya, TurkeydThoracic Surgery Department, The Faculty of Medicine, Gazi University, Ankara, TurkeyePathology Department, Ataturk Chest Disease and Thoracic Surgery Center, Ankara, Turkey

Received 8 June 2005; accepted 25 October 2005

It was presented at the 14th European Respiratory Society Annual Congress in Glasgow, UK, September 4–8, 2004.

KEYWORDSPulmonary blastoma;Thoracic surgery;Survival

ee front matter & 2005med.2005.10.026

ing author. +90 262 3037ess: tubaliman@kou.ed

Summary Pulmonary blastoma is a rare malignant lung tumor with a poorprognosis. It is composed of immature mesenchymal and epithelial components thatresemble fetal lung tissue. We aimed to share our treatment results in biphasicpulmonary blastoma.

In Ataturk Chest Disease and Thoracic Surgery Center, five patients with biphasicpulmonary blastoma (four men, one woman, aged between 27 and 61—mean 39.4)were treated between 1987 and 2000 (0.3% of operated NSCC). Hemoptysis, cough,chest pain and dyspnea were the symptoms. Anemia and high erythrocytesedimentation rate were determined in two patients. Radiological examinationsrevealed a mass in four patients and massive pleural effusion in one. None of thepatients were diagnosed preoperatively and hence all patients underwentexploratory thoracotomy. Three lobectomy, one pneumonectomy and one wedgeresection were performed.

Histopathological examinations revealed biphasic pulmonary blastoma in all thepatients. Pathological stagings were as follows: 1 patient in T1N0M0 and 1 patient inT2N0M0 (198 and 112 months survival, respectively), three patients in T2N1M0(9,10,17 months survival). In follow up period, prostate carcinoma and rectumcarcinoma were detected as second primary tumors in the patient in stageT2N0M0.

In patients who have small size tumors without nodal involvement, long-termsurvival can be obtained with radical surgery; even in biphasic pulmonary blastomas.

Elsevier Ltd. All rights reserved.

407; fax: +90 262 3038 003.u.tr (S.T. Liman).

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Pulmonary blastoma 1175

According to our limited experiences, N1 nodal involvement shows very poorprognosis.& 2005 Elsevier Ltd. All rights reserved.

Introduction

Pulmonary blastomas (PB) are malignant tumors ofuncertain histogenesis that histologically resemblesthe developing in early fetal life. It was hypote-sized that it originated from immature pulmonary‘‘blastema’’ pleuropotential tissue capable ofdifferentiating into both mesenchymal and epithe-lial portions of the peripheral lungs.1 There areseen very rarely, 0.5% of all primary lung tumors.2

PB are divided into three sub-groups: biphasicpulmonary blastoma (PB), well differentiated fetaladenocarcinoma (WDFA) and pleuropulmonary blas-toma (PPB). WDFA are tumors which containsepithelial malignant component without mesench-ymal malignancy. PPB indicates tumors with me-senchymal malignancy but without epithelialmalignant component. PB are chacterized by adual or biphasic immature cellular component bothare malignant (epithelial and mesenchymal). Herewe presented five biphasic pulmonary blastoma andthe results of our treatment.

Patients

Between 1987 and 2000, we operated 1411 caseswith NSCLC in Ataturk Chest Disease and ThoracicSurgery Center. Five of them were biphasic PB(0.3%).

There was a male predominance in the patientswith PB. Their ages ranged between 27 and 61years. Three of them were smokers. Patients’characteristics were summarized in Table 1.

The most frequently seen complaints werecough, hemoptysis and chest pain. Anemia andhigh erythrocyte sedimentation rates were de-tected in two patients with big tumors.

Chest X-ray and thorax tomography were per-formed in all patients (Figs. 1 and 2). In fourpatients, radiological examinations revealed soli-tary pulmonary mass. In one patient, first examina-tions showed massive pleural effusion andempyema was detected via thoracentesis. Afterchest tube drainage, solitary big pulmonary masswas observed in his chest X-ray.

Tumors were located in lower lobes in threepatients, in upper lobe in one and in middle lobe inone patient.

Bronchoscopy was performed in all patients andendobronchial tumor was observed in three. Butbronchoscopic biopsy was not diagnostic in thosepatients.

Diagnosis could not be obtained in all of thepatients preoperatively and they all underwentthoracotomy. Wedge resection was performed inone patient, lobectomy in three and pneumonect-omy in one patient. Wedge resection was per-formed since frozen section examination could notbe performed. He was advised to have a secondoperation, but he refused. When recurrences wasdetected in his 3 months follow up after surgery, heaccepted the operation and lobectomy was per-formed.

Staging was defined in accordance with the lungcancer staging system. Survivals were measuredfrom the time of diagnosis.

Results

All patients were diagnosed as biphasic pulmonaryblastoma after histopathological examination ofthe specimens. Lymph node involvement weredetected in three cases with larger tumors(Table 1). There were one patient in T1N0M0,one pateint in T2N0M0 and three patients inT2N1M0.

Bronchopleural fistula was occured in thepatient who underwent pnemonectomy (T2N1M0).Thoracomyoplasty was performed as a secondoperation in that case. In his follow up periodlocal recurrence was developed. Esophageal andcardiac involvement were detected. He had4000 rad radiotherapy. But treatment was unsuc-cessful and he died in his 9th month of follow upperiod.

In two patients (T2N1M0) systemic metastasiswere detected in follow up and chemotherapy wasgiven. But there was no response to chemotherapyand they died. Survivals of those patients werewere 10, 17 months.

Two patients with tumors 3 cm (T1N0M0) and3.6 cm (T2N0M0) in size had long-term survivals,198 and 112, respectively. First patient is stillalive. Two different carcinoma were occurred inthe second patient while follow up. He wasgiven treatment for prostate carcinoma and

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Table

1Cha

racteristics

ofthepatients.

Num

ber

Age

,sex

Symptoms

Physical

exam

ination

Laboratory

exam

inations

Loca

lization

,diameter

Endob

ronc

hial

lesion

Operation

Tnm

Additiona

ltrea

tmen

tAdditiona

ldisea

seSu

rvival

(mon

th)

I61

,m

Cou

gh,ch

est

pain

Nopositive

find

ing

Nopositive

find

ing

Right

lower

lobe,

3.6cm

+Rll

T2n

0m0

—Prostatca

,rectal

carcinom

a

112dieddilated

cardiomyo

pathia

Ii28

,m

Cou

gh,ch

est

pain

Nopositive

find

ing

Nopositive

find

ing

Left

lower

lobe,

3cm

+Wed

geLLL

T1n

0m0

——

198alive

Iii27

,f

Cou

gh,ch

est

pain,

hemop

tysis

Nopositive

find

ing

Ane

mia,high

ERS

Right

upper

lobe,

6cm

—Rul

T2n

1m0

Vincristine

+Cyclopho

spha

mide,

3cu

res,

Ifospha

mid+E

toposite,

2cu

res

—17

diedBon

e,live

r,brain

metastatis

(nasoc

omial

pne

umon

ia)

Iv27

,m

Cou

gh,

hemop

tysis,

feve

r,dyspne

a

Dim

inishe

drespiratory

soun

ds

Ane

mia,high

ERS,

leuc

ocytosis,

empye

ma

Right

middle

lobe,

17cm

+Rptm

pT2n

1m0

4000

radRT

—9died(loc

alrecu

rren

ce,

esop

hagial

and

cardiac

invo

lvem

ent)

V54

,m

Hem

optysis

Nopositive

find

ing

Nopositive

find

ing

Right

lower

lobe,

6.5cm

—Rll

T2n

1m0

Vincristine

+cyclopho

spha

mide,

3cu

res

—10

died(bon

emetastasis)

M:male,

F:female,

ERS:

erythroc

ytesedimen

tation

rate,RLL:righ

tlower

lobec

tomy,

LLL:

left

lower

lobec

tomy,

RUL:

righ

tup

perlobec

tomy,

RP:righ

tpne

umon

ectomy,

TMP:

thorac

omyo

plastia.

S.T. Liman et al.1176

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Figure 2 Posteroanterior and CT scan appearance of asolitary mass in the right lower lobe.

Figure 1 Posteroanterior and CT scan appearance oflobulated circumscribed large mass with heterogenousenhancement in the middle lobe of the right lung.

Pulmonary blastoma 1177

rectal carcinoma and he died because of thecomplications of chemotherapy for rectal carcino-ma in his 112th months.

Conclusion

Pulmonary blastomas (PB) are rarely seen tumors.They are composed of both mesenchymal andepithelial components which resemble fetal lungtissue morphologically with a frequency of only0.5% of all primary lung tumors.2 It has been shownthat the tumor arises from the endodermal tissue orthat it originates in pleuropotential stem cells.3,4

Some authors consider pulmonary blastoma torepresent a variant of carcinosarcoma.5 There werethree types of PB. Biphasic PB have two malignantcomponents; epithelial and mesenchymal. Theprognosis of biphasic blastoma is much worse thanthe others.

The etiology and predisposing factors are not stillfully understood. In the literature, there is strongevidence showing the correlation between cigar-ette smoking and PB.6,7

They may occur at all ages but predominantlycommon in adults (the peak incidence in the fourthdecade of life). There is a male predominance.2

When compared to the operated nonsmall celllung carcinomas, PB are rare, large and sympto-matic tumors which affect younger age groups andhave poor prognosis.8 Approximately 60% of thepatients are symptomatic.9–11 All of our patientswere symptomatic. We detected anemia in twopatients who had larger tumors and nodal involve-ments.

Biphasic blastomas are usually located in theperiphery of the lung.12 Only 25% exhibit endo-bronchial growth.13,14 Three of our patients hadendobronchial tumor but bronchoscopic biopsies

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S.T. Liman et al.1178

were not diagnostic. Pleural effusions occur in aminority of cases. It sometimes may be infectedcausing empyema like in one of our patients.

Considerable immunoreactivity for alpha-feto-protein (AFP) was reported in the literature.15,16 Itwas pointed out that the epithelial cells of PB mightoccasionally de-differentiate into cells functionallyresembling fetal hepatic, foregut and yolk sac cellsexpressing AFP.15 Unfortunately AFP levels were notmeasured in our patients.

In radiological examinations, PB manifest as asolitary pulmonary nodule or mass with a smoothmargin because of the desmoplastic change sur-rounding the mass. Generally, the tumor hasmassive necrosis.17 The tumor rarely appear to becavitated, calcified or multiple.

Despite bronchoscopy, mediastinoscopy, thoraco-scopy, percutaneous and transbronchial biopsies,PB cannot be diagnosed preoperatively due to thelack of cellular material and extensive necrosis ofthe lesions.18 We also could not diagnose pulmonaryblastoma preoperatively.

The best treatment of pulmonary blastoma issurgery in the early stages of the disease. Adjunc-tive therapy is still controversial because of lack ofdata. Rare cases, which have good responds tochemotherapy and radiotherapy, have been re-ported in the literature whereas in the majority ofcases recurrences are seen.19–21 Cutler et al.treated and reviewed the chemotherapy literaturefor PB and recommended cisplatin and etoposidetreatment as effective regimes.15 Neoadjuvantchemotherapy for downstaging advanced tumorscan be used before surgical resections.7 Recur-rences are mostly seen with the incidence of 43%,1–11 months after surgery.18 Recurrences mostcommonly occur in the brain, mediastinum, pleura,liver, diaphragm, heart and soft tissues of extre-mities.18

Nodal involvement is almost always associatedwith the tumor size and also poor prognosis inbiphasic PB.6

Based on our limited experience, resection ofsmall tumors, which do not have any lymph nodeinvolvement, can provide better survival withoutany additional treatment. Wedge resection shouldnot be performed in PB. In one of our patient, therewas a recurrence due to the inadequate surgicalprocedure (wedge resection). That patient under-went second operation, he did not have any nodalinvolvement and he has the best survival time inthis small serie. In our cases adjuvant chemothera-pies were not effective.

Finally, in the patients with small size tumors,which do not have nodal involvement, long-termsurvival can be obtained with surgery even if it is

biphasic pulmonary blastoma. According to ourlimited experiences, N1 nodal involvement showsvery poor prognosis even tumor is resected com-pletely. Unfortunately, we still do not know theefficiency of the adjuvant chemotherapy and radio-therapy treatment. Multi-institutional treatmentprotocols in a sufficient number of patients shouldbe performed.

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