ARTICLE IN PRESS
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: [email protected]
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).
ARTICLE IN PRESS
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
ARTICLE IN PRESS
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
ARTICLE IN PRESS
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
ARTICLE IN PRESS
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.
References
1. Spencer H. Pulmonary blastoma. J Pathol 1961;82:161.2. Larsen H, Sorensen JB. Pulmonary blastoma: a review with
special emphasis on prognosis and treatment. Cancer TreatRev 1996;22:145–60.
3. Berean K, Truong LD, Dudley AW, Cagle PT. Immunohisto-chemical characterization of pulmonary blastoma. Am J ClinPathol 1988;89:773–7.
4. Korbi S, M’Boyo A, Dusmet M, Spiliopoulos A. Pulmonaryblastoma. Immunohistochemical and ultrastructural studiesof a case. Histopathology 1987;11:753–60.
5. Roth JA, Elguezabal A. Pulmonary blastoma evolving intocarcinosarcoma. A case study. Am J Surg Pathol1978;2(4):407–13.
6. Koss MN, Hochholzer L, O’Leary T. Pulmonary blastomas.Cancer 1991;67:2368–81.
7. Zaidi A, Zamvar V, Macbeth F, Gibbs AR, Kulatilake N,Butchart EG. Pulmonary blastoma: medium-term resultsfrom a regional center. Ann Thorac Surg 2002;73:1572–5.
8. Robert J, Pache JC, Seium Y, de Perrot M, Spiliopoulos A.Pulmonary blastoma: report of five cases and identificationof clinical features suggestive of the disease. Eur JCardiothorac Surg 2002;22(5):708–11.
9. LeMense GP, Reed CE, Silvestri GA. Pulmonary blastoma: arare lung malignancy. Lung Cancer 1996;15:233–7.
10. Di Lieto E, Baldi A, Vicidomini G, Di Marino MP, Baldi F.Pulmonary blastoma in adults. Minerva Chir 1997;52:839–46.
11. Dogan R, Gungen Y, Ucanok K, Cetin G. Pulmonary blastoma.Hacettepe Medical Journal 1989;22:235–9.
12. Majid OA, Rajendran U, Baker LT. Pulmonary blastoma. AnnThorac Cardiovasc Surg 1998;4:47–52.
13. Berho M, Moran CA, Suster S. Malignant mixed epithelial/mesenchymal neoplasms of the lung. Semin Diagn Pathol1995;12:123–39.
14. Jacobsen M, Francis D. Pulmonary blastoma. A clinico-pathological study of eleven cases. Acta Pathol MicrobiolScand 1980;88:151–60.
15. Inoue H, Kasai K, Shinada J, Yoshimura H, Kameya T.Pulmonary blastoma. Comparison between its epithelialcomponents and fetal bronchial epithelium. Acta Pathol Jpn1992;42:884–92.
16. Kasuga I, Miyamoto D, Ichinose Y, et al. Alpha-fetoproteinproducing pulmonary blastoma in a patient with systemicsclerosis: pathogenetic analysis. Eur Respir J1998;11:1185–7.
17. Lee HJ, Goo JM, Kim KW, Im JG, Kim JH. Pulmonaryblastoma radiologic findings in five patients. Clin Imag2004;28:113–8.
18. Novotny JE, Hurias CM. Resection and adjuvant chemother-apy of pulmonary blastoma: a case report. Cancer1995;76:1537–9.
ARTICLE IN PRESS
Pulmonary blastoma 1179
19. Cutler CS, Michel RP, Yassa M, Langleben A. Pulmonaryblastoma: case report of a patient with a 7-year remissionand review of chemotherapy experience in the worldliterature. Cancer 1998;82:462–7.
20. Surmont VF, van Klaveren RJ, Nowak PJ, Zondevan PE,Hoogsteden HC, van Meerbeeck JP. Unexpected response of
a pulmonary blastoma on radiotherapy: a case reportand review of the literature. Lung Cancer 2002;36:207–11.
21. Hasturk S, Erdogan Y, Cakiroglu E, Teke Y. PulmonerBlastoma (bir olgu nedeniyle). Turk Hematol Onkol Derg1993;3:116–20.
Top Related