ITAL J PEDIATR 2006;32:122-125udCASE REPORTudCASO CLINICOudPleuropulmonary blastoma: a differential diagnosis of chronic cough. Long-term survival after multimodal aggressive therapyudBlastoma pleuro-polmonare: rara diagnosi differenziale da tosse cronica.udRemissione a lungo termine dopo aggressiva terapia multimodaleudP. D''ANGELO, V. MANZO*, S. VENEZIA*, R. ALAGGIO", E SIRACUSA*,udM. LO CURTO*udUnità Operativa di Oncoematologia Pediatrica, Ospedale dei Bambini " G . Di Cristina",udPalermo; * Dipartimento Materno Infantile, Università di Palermo; ** Istituto di AnatomiaudPatologica, Università di PadovaudSummaryudPleuropulmonary blastoma (PPB) in childhood is a rare clinicopathologic entity distinctudfrom adult pneumoblastoma. This tumour may originate from the lung, the pleura, or theudmediastinum; it can metastasize and is usually associated with a poor outcome. We reportudthe case of a 5-year-old boy who developed PPB manifesting with respiratory distress. Atudthe standard x-ray and magnetic resonance imaging of the chest there was opacity coveringudthe entire right lung. The histological and immunohistological tests led to the diagnosisudof blastematous, malignant mesenchymatous PPB with pluridirectional differentiation.udTreatment consisted of preoperative chemotherapy to reduce tumour volume, completeudsurgical resection of the residuai tumour mass, and post-surgical chemotherapy. Followingudthis approach, the child is alive in continuous complete remission 9 years after diagnosis.udRiassuntoudII Blastoma Pleuro-Polmonare (BPP) infantile è un ''entità clinico patologica ben distintauddal Pneumoblastoma dell''adulto. Questo tumore può prendere origine dal polmone, dallaudpleura o dal mediastino; può metastatizzare e ha spesso una prognosi infausta. Riportiamoudil caso di un bambino di 5 anni, in cui il BPP si manifestò con un distress respiratorio;udla radiografia del torace e la Risonanza Magnetica hanno evidenziato una grossaudmassa che occupava l''emitorace destro. L''esame istopatologico ha permesso di porreuddiagnosi di BPP. Il paziente è stato trattato con chemioterapia, che ha ridotto il volumeuddella massa, con asportazione del tumore e chemioterapia post-operatoria; tale trattamentoudha consentito i''eradicazione della malattia; il paziente è in remissione completaudcontinua a 9 anni dalla diagnosi.udIntroductionudPleuropulmonary blastoma (PPB) is an extremely rare and aggressive malignancyudof childhood. It was originally described as a distinct entity by Maniveludet al. ''. Prior to its identification it was reported in the early literature byudSpencer as pulmonary blastoma or embryonic sarcoma 2.udIt is characterized by primitive mesenchymal tissue and epithelial tubularudstructures resembling the foetal lung. The eponymous PPB defines the paediatricudvariety of pulmonary blastoma. In PPB, the dysembrionic neoplasmudshows blastematous and sarcomatous components and a lack of carcinomatousudcomponents (which are instead present in adult pulmonary blastoma),udsometimes on previous dysplastic pulmonary conditions 3 . PPB is classifiedudin 3 subtypes: type I (cystic), type II (mixed solid and cystic) and type IIIud(solid)4.udKey wordsudPleuropulmonary blastoma •udChildhood lung cancer • AdjuvantudchemotherapyudParole chiaveudBlastoma pleuropolmonare •udTumore polmonare infantile •udChemioterapia post-operatoriaudSubmitted: March 16, 2005udAccepted: July 19, 2005udCorrespondence:udProf. Margherita Lo CurtoudDipartimento di PediatriaudUniversità di PalermoudIstituto Materno Infantileudvia Cardinale Rampolla 1udPalermo, ItalyudTel. +39 091 6555476udE-mail:udmargheritalocurto@virgilio.it.ud122udPLEUROPULMONARY BLASTOMA IN A CHILDudThe predominant clinical features are cough, tachypnea,udfever, respiratory distress; secondary pneumothoraxud5 and chest pain have also been reported 6. Sinceudthese features are not specific, an infectious disease isudoften erroneously diagnosed; hence, when eventuallyuddetected, the neoplasm is often very large, may even involveudan entire hemithorax, and present metastases.udDespite the different therapeutic procedures - surgery,udchemotherapy and radiotherapy - prognosis is oftenudpoor: Indolfi et al. 7 report 42% and Priest et al. 6 45%udof event free survival (EFS) at 2 years. Poor prognosticudfactors are histological subtype II or III6 , a maximumuddiameter greater than 5 cm 7 , failure to completely removeudthe mass, extrapulmonary effusion such as pleuraudor pericardium, metastases 8.udWe report the case of a five-year-old child who, despiteudthe large tumour size at diagnosis and histological subtypeudII, after a treatment with chemotherapy before andudafter surgery, is in continuous complete remissionud(CCR) nine years after the diagnosis.udCase reportudA 5-year-old boy was admitted to our ward for hyporexia,udcough, shortness of breath, progressive thinningudand pallor in the previous 2 months. The physicaludexamination showed poor clinical conditions, tachydyspneaud(R.F. 45/min.), hypophonesis and reduction ofudthe physiologic vescicular murmure of the middle andudlower regions of the right lung, meteoric abdomen withudthe liver margin 5 cm below the right costai margin.udThe results of the laboratory investigations were Hb 8.5udg/dl, white blood cells 18.800/ul (N 68%, L 22%, Mud6%, E 4%), platelets 611.000/u.l, VES (K.I.) 65, CRPud2.4 mg/dl; serum levels of copper 168 ixg/dl, ferritinud292 ng/dl, LDH 1.261 u/1, oc-FP 6.3 u/1.udChest radiographs showed a bulky mass in the rightudhemithorax displacing the mediastinum leftward andudthe liver downward (Fig. 1).udThe thoracic-abdominal ultrasound scan showed audpoorly confined voluminous mass, having diameters ofud120 x 86 mm, with echogenic-hyperechogenic structureudand some hypo-anechogenic areas, arising in rightudhemithorax and displacing the liver and right kidneyuddownwards.udA magnetic resonance imaging (MRI) of the thoraxudshowed a mass involving entirely the right hemitorax,udwith a centrai hemorrhagic component that displacedudthe mediastinum and the heart to the left.udThe patient underwent surgical thoracotomy, which revealedudan unencapsulated mass with smooth surfaceudand tense-elastic consistency, entirely covered by pleura,udnot adherent to the thoracic wall; since the conspicuousudextension of the mass did not allow resection, onlyuda biopsy was performed.udMicroscopically, the biopsy specimen showed a predominantlyudsolid neoplasm with focal cysts. The tumourudcontained mesenchymal elongated cells arrangedudin sheets, and more primitive blastematous foci. ThereudFig. 1. Posterior-anterior chest radiograph at presentation,udshowing a bulky mass, displacing the mediastinum.udwas no evidence of typical rhabdomyoblasts or cartilage.udCysts exhibited an epithelial lining, with flattenedudto columnar cells and an underlying layer of primitiveudmesenchymal cells. The morphologic appearance wasudconsistent with a diagnosis of PPB type II. Immunostainsudemphasized the doublé component with a positiveudstaining for cytokeratin (MNF116, pancytokeratin) inudthe epithelial component and a positive vimentin stainingudin mesenchymal component. Occasionai spindleudcells were positive for desmin; oc-fetoprotein, S-100udprotein, CD99, NB84A were negative in both the epithelialudand the stremai component.udIn order to stage the disease the patient underwent totaludbody bone scan with "Tc-MDP, brain and abdominaludCT scan, and bone marrow aspirate; no metastaticudspread was detected, and a stage III was defined.udThe child underwent chemotherapy with carboplatinumud(CBP) 400 mg/m2 + etoposide (VP16) 150 mg/m2 daysud1, 2; vincristine (VCR) 1.5 mg/m2 + actinomycin-Dud(ACT-D) 1.5 mg/m2 day 21 + ifosfamide (IFO) 1500udmg/m2 days 21-23, for overall 3 cycles; thereafter, 2 cyclesudwere scheduled, including VCR 1.5 mg/m2 + ACTDud1.5 mg/m2 day 1, doxorubicin 40 mg/m2 days 1-2 andudIFO 1500 mg/m2 days 1-3. The number of cycles wereudestablished according to the features of imaging studies.udA chest x-ray survey showed a very good responseud(Fig. 2) to chemotherapy. Six months after the diagnosisudcomplete resection of the tumour was performedudthrough a right posterior-lateral thoracotomy by theudfifth intercostal space. The tumour was capsulated andudlocated between the upper and middle lobe of the rightudlung, displacing caudally the middle and lower pulmonaryudlobes. The centrai zone of the mass was composedudof hyalinized fibrous stroma nodules and veryudsmall fragments of blastomatosous tumoral tissue, atudabout 2 cm from the resection borders. The neoplasmudwas almost entirely necrotic.ud123udP. D''ANGELO ET AL.udFig. 2. Posterior-anterior chest radiograph, after chemotherapy,udbefore surgical excision.udAfter surgery the patient underwent 2 more cycles ofudchemotherapy with CBP 400 mg/m2 + VP 16 150udmg/m2/day x 2 days.udThere was clinical and imaging evidence of a progressiveudnormalisation of lung morphology and function.udThe patient was monitored with clinical and radiologicaludinvestigations according to the following schedule:udchest radiograms every 3 months the first year, every 6udmonths the second and third year, every 12 months forudthe 4t h, 5l h and 6* year; MRI at 1 and 3 years after withdrawaludof therapy.udNine years after the diagnosis, the child is in continuousudcomplete remission.udDiscussionudPPB in childhood is very rare. Our patient, as most ofudthose reported in the literature 5 8 , presented unspecificudrespiratory symptoms; the x-ray revealed a large intrathoracicudmass, suggesting the need for further imagingudstudies. It is important to emphasize the role of anudearly imaging examination (x-ray, ultrasound scan, CTudor MRI) to detect as soon as possible the mass, in orderudto proceed to more specific investigations to elucidateudthe nature and staging of this malignant tumour. Radiographicudfindings of pleuropulmonary blastoma are notudspecific, especially when most of the neoplasm is cystic,udresembling the radiographic features of teratoma.udIn this respect we note that PPB may initially manifestudwith clinical and radiologie signs and symptoms ofudpneumothorax 5 and may arise from other dysplasticudconditions; as a matter of fact, cystic pulmonary adenomatoidudmalformation (CPAM) can be associatedudwith PPB, which is also described in association withudsome congenital dysembriogenic abnormalities as cysticudnephroma 3 . The clinical and radiological presentationudin our patient showed mediastinal involvement;udthe mass was not excisable at the first surgical look becauseudthe neoplasm involved the pleura and was veryudlarge. The histopathologic diagnosis was consistentudwith type II PPB.udThe features described usually correlate with a poorudprognosis 6 8 . The patient was submitted to intensiveudmultiagent neoadiuvant chemotherapy, which reducedudthe tumour mass, making the complete surgical resectionudfeasible, and allowing eradication of the malignancy.udSuch intensive multiagent chemotherapy is in most casesudnecessary for the reduction and complete excision ofudthe tumor, which represents the most favourable factorudfor long term survival.udIn a recent report describing 11 patients 7 , two underwentudtotal excision of the tumour at diagnosis, andudwere both alive without disease at 23 and 132 monthsudrespectively, with no adjuvant chemotherapy administeredudin the latter; another 3 patients remained diseaseudfree, two after macroscopic total resection and polychemotherapyudand one after polychemotherapy and delayedudcomplete surgery.udThe effectiveness of chemotherapy has also been reportedudby other Authors 8 1°. The choice of the antiblasticudagents used in our patients was due to their knownudeffectiveness on mesenchymal and epithelial tumors n.udOur patient was not treated with radiotherapy, whichudhas proven to be effective in few patients 1.udIn conclusion, this case suggests that PPB may be takenudin consideration for the differential diagnosis in respiratoryuddistress. According to our experience and toudother literature reports, total remission of this conditionudmay be achieved with complete surgical excision (primaryudor delayed) and intensive chemotherapy.udReferencesud1 Manivel JC, Priest JR, Watterson J, Steiner M, Woods WG, WickudMR. Pleuropulmonary blastoma: the so called pulmonary blastomaudof childhood. Cancer 1988;62:1516-26.ud2 Spencer H. Pulmonary blastoma. J Pathol Bacteriol 1961 ;82:161-5.ud3 Priest JR, Watterson J, Woods WG, Brid RI. Pleuropulmonaryudblastoma: a marker forfamilial disease. J Pediatr 1996;128:220-4.ud4 Dehner LP. Watterson J, Priest J. Pleuropulmonaiy blastoma. Audunique intrathoracìc-pulmonary neoplasm of childhood. In: AskinudFB, Langston C, Rosemberg HS, eds. Pulmonary disease: perspectivesudin pediatrie pathology. Basel: Karger 1995, p. 214-26.ud5 Guler E, Kutluk MT, Yalcin B, Cila A, Kale G, BuyukpamukcuudM. Pleuropulmonary blastoma in a child presenting with pneumothorax.udTumori 2001;87:340-2.ud6 Priest JR, McDermott MB, Bathia S, Watterson J, Manivel JC,udDehner LP. Pleuropulmonary blastoma. A clinic-pathologic studyudofSOcases. Cancer 1997;80:146-61.ud7 Indolfi P, Casale F, Carli M, Bisogno G, Ninfo V, Cecchetto G, etudal. Pleuropulmonary blastoma: management and prognosis of 11udcases. Cancer 2000;89:1396-401.ud8 Romeo C, Impellizzeri P, Grosso M, Vitarelli E, Gentile C. Pleu-ud124udPLEUROPULMONARY BLASTOMA IN A CHILDudropulmonary blastoma: long-term survival and literature review.udMed Pediatr Oncol 1999;33:372-6.udParsons SK, Fishman SJ, Hoorntje LE, Jaramillo D, Marcus KC,udPerez-Atayde AR, et al. Aggressive multimodal treatment of pleuropulmonaryudblastoma. Ann Thorac Surg 2001;72:939-42.udOzkajnak MF, Ortega JA, Laug W, Gilsanz V, Isaacs H Jr. Role ofudchemotherapy in pediatrie pulmonary blastoma. Med Pediatr Oncolud1990;18:53-6.ud125
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