ITAL J PEDIATR 2006;32:122-125
CASE REPORT
CASO CLINICO
Pleuropulmonary blastoma: a differential diagnosis of chronic cough. Long-term survival after multimodal aggressive therapy
Blastoma pleuro-polmonare: rara diagnosi differenziale da tosse cronica.
Remissione a lungo termine dopo aggressiva terapia multimodale
P. D''ANGELO, V. MANZO*, S. VENEZIA*, R. ALAGGIO", E SIRACUSA*,
M. LO CURTO*
Unit\ue0 Operativa di Oncoematologia Pediatrica, Ospedale dei Bambini " G . Di Cristina",
Palermo; * Dipartimento Materno Infantile, Universit\ue0 di Palermo; ** Istituto di Anatomia
Patologica, Universit\ue0 di Padova
Summary
Pleuropulmonary blastoma (PPB) in childhood is a rare clinicopathologic entity distinct
from adult pneumoblastoma. This tumour may originate from the lung, the pleura, or the
mediastinum; it can metastasize and is usually associated with a poor outcome. We report
the case of a 5-year-old boy who developed PPB manifesting with respiratory distress. At
the standard x-ray and magnetic resonance imaging of the chest there was opacity covering
the entire right lung. The histological and immunohistological tests led to the diagnosis
of blastematous, malignant mesenchymatous PPB with pluridirectional differentiation.
Treatment consisted of preoperative chemotherapy to reduce tumour volume, complete
surgical resection of the residuai tumour mass, and post-surgical chemotherapy. Following
this approach, the child is alive in continuous complete remission 9 years after diagnosis.
Riassunto
II Blastoma Pleuro-Polmonare (BPP) infantile \ue8 un ''entit\ue0 clinico patologica ben distinta
dal Pneumoblastoma dell''adulto. Questo tumore pu\uf2 prendere origine dal polmone, dalla
pleura o dal mediastino; pu\uf2 metastatizzare e ha spesso una prognosi infausta. Riportiamo
il caso di un bambino di 5 anni, in cui il BPP si manifest\uf2 con un distress respiratorio;
la radiografia del torace e la Risonanza Magnetica hanno evidenziato una grossa
massa che occupava l''emitorace destro. L''esame istopatologico ha permesso di porre
diagnosi di BPP. Il paziente \ue8 stato trattato con chemioterapia, che ha ridotto il volume
della massa, con asportazione del tumore e chemioterapia post-operatoria; tale trattamento
ha consentito i''eradicazione della malattia; il paziente \ue8 in remissione completa
continua a 9 anni dalla diagnosi.
Introduction
Pleuropulmonary blastoma (PPB) is an extremely rare and aggressive malignancy
of childhood. It was originally described as a distinct entity by Manivel
et al. ''. Prior to its identification it was reported in the early literature by
Spencer as pulmonary blastoma or embryonic sarcoma 2.
It is characterized by primitive mesenchymal tissue and epithelial tubular
structures resembling the foetal lung. The eponymous PPB defines the paediatric
variety of pulmonary blastoma. In PPB, the dysembrionic neoplasm
shows blastematous and sarcomatous components and a lack of carcinomatous
components (which are instead present in adult pulmonary blastoma),
sometimes on previous dysplastic pulmonary conditions 3 . PPB is classified
in 3 subtypes: type I (cystic), type II (mixed solid and cystic) and type III
(solid)4.
Key words
Pleuropulmonary blastoma \u2022
Childhood lung cancer \u2022 Adjuvant
chemotherapy
Parole chiave
Blastoma pleuropolmonare \u2022
Tumore polmonare infantile \u2022
Chemioterapia post-operatoria
Submitted: March 16, 2005
Accepted: July 19, 2005
Correspondence:
Prof. Margherita Lo Curto
Dipartimento di Pediatria
Universit\ue0 di Palermo
Istituto Materno Infantile
via Cardinale Rampolla 1
Palermo, Italy
Tel. +39 091 6555476
E-mail:
[email protected].
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PLEUROPULMONARY BLASTOMA IN A CHILD
The predominant clinical features are cough, tachypnea,
fever, respiratory distress; secondary pneumothorax
5 and chest pain have also been reported 6. Since
these features are not specific, an infectious disease is
often erroneously diagnosed; hence, when eventually
detected, the neoplasm is often very large, may even involve
an entire hemithorax, and present metastases.
Despite the different therapeutic procedures - surgery,
chemotherapy and radiotherapy - prognosis is often
poor: Indolfi et al. 7 report 42% and Priest et al. 6 45%
of event free survival (EFS) at 2 years. Poor prognostic
factors are histological subtype II or III6 , a maximum
diameter greater than 5 cm 7 , failure to completely remove
the mass, extrapulmonary effusion such as pleura
or pericardium, metastases 8.
We report the case of a five-year-old child who, despite
the large tumour size at diagnosis and histological subtype
II, after a treatment with chemotherapy before and
after surgery, is in continuous complete remission
(CCR) nine years after the diagnosis.
Case report
A 5-year-old boy was admitted to our ward for hyporexia,
cough, shortness of breath, progressive thinning
and pallor in the previous 2 months. The physical
examination showed poor clinical conditions, tachydyspnea
(R.F. 45/min.), hypophonesis and reduction of
the physiologic vescicular murmure of the middle and
lower regions of the right lung, meteoric abdomen with
the liver margin 5 cm below the right costai margin.
The results of the laboratory investigations were Hb 8.5
g/dl, white blood cells 18.800/ul (N 68%, L 22%, M
6%, E 4%), platelets 611.000/u.l, VES (K.I.) 65, CRP
2.4 mg/dl; serum levels of copper 168 ixg/dl, ferritin
292 ng/dl, LDH 1.261 u/1, oc-FP 6.3 u/1.
Chest radiographs showed a bulky mass in the right
hemithorax displacing the mediastinum leftward and
the liver downward (Fig. 1).
The thoracic-abdominal ultrasound scan showed a
poorly confined voluminous mass, having diameters of
120 x 86 mm, with echogenic-hyperechogenic structure
and some hypo-anechogenic areas, arising in right
hemithorax and displacing the liver and right kidney
downwards.
A magnetic resonance imaging (MRI) of the thorax
showed a mass involving entirely the right hemitorax,
with a centrai hemorrhagic component that displaced
the mediastinum and the heart to the left.
The patient underwent surgical thoracotomy, which revealed
an unencapsulated mass with smooth surface
and tense-elastic consistency, entirely covered by pleura,
not adherent to the thoracic wall; since the conspicuous
extension of the mass did not allow resection, only
a biopsy was performed.
Microscopically, the biopsy specimen showed a predominantly
solid neoplasm with focal cysts. The tumour
contained mesenchymal elongated cells arranged
in sheets, and more primitive blastematous foci. There
Fig. 1. Posterior-anterior chest radiograph at presentation,
showing a bulky mass, displacing the mediastinum.
was no evidence of typical rhabdomyoblasts or cartilage.
Cysts exhibited an epithelial lining, with flattened
to columnar cells and an underlying layer of primitive
mesenchymal cells. The morphologic appearance was
consistent with a diagnosis of PPB type II. Immunostains
emphasized the doubl\ue9 component with a positive
staining for cytokeratin (MNF116, pancytokeratin) in
the epithelial component and a positive vimentin staining
in mesenchymal component. Occasionai spindle
cells were positive for desmin; oc-fetoprotein, S-100
protein, CD99, NB84A were negative in both the epithelial
and the stremai component.
In order to stage the disease the patient underwent total
body bone scan with "Tc-MDP, brain and abdominal
CT scan, and bone marrow aspirate; no metastatic
spread was detected, and a stage III was defined.
The child underwent chemotherapy with carboplatinum
(CBP) 400 mg/m2 + etoposide (VP16) 150 mg/m2 days
1, 2; vincristine (VCR) 1.5 mg/m2 + actinomycin-D
(ACT-D) 1.5 mg/m2 day 21 + ifosfamide (IFO) 1500
mg/m2 days 21-23, for overall 3 cycles; thereafter, 2 cycles
were scheduled, including VCR 1.5 mg/m2 + ACTD
1.5 mg/m2 day 1, doxorubicin 40 mg/m2 days 1-2 and
IFO 1500 mg/m2 days 1-3. The number of cycles were
established according to the features of imaging studies.
A chest x-ray survey showed a very good response
(Fig. 2) to chemotherapy. Six months after the diagnosis
complete resection of the tumour was performed
through a right posterior-lateral thoracotomy by the
fifth intercostal space. The tumour was capsulated and
located between the upper and middle lobe of the right
lung, displacing caudally the middle and lower pulmonary
lobes. The centrai zone of the mass was composed
of hyalinized fibrous stroma nodules and very
small fragments of blastomatosous tumoral tissue, at
about 2 cm from the resection borders. The neoplasm
was almost entirely necrotic.
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P. D''ANGELO ET AL.
Fig. 2. Posterior-anterior chest radiograph, after chemotherapy,
before surgical excision.
After surgery the patient underwent 2 more cycles of
chemotherapy with CBP 400 mg/m2 + VP 16 150
mg/m2/day x 2 days.
There was clinical and imaging evidence of a progressive
normalisation of lung morphology and function.
The patient was monitored with clinical and radiological
investigations according to the following schedule:
chest radiograms every 3 months the first year, every 6
months the second and third year, every 12 months for
the 4t h, 5l h and 6* year; MRI at 1 and 3 years after withdrawal
of therapy.
Nine years after the diagnosis, the child is in continuous
complete remission.
Discussion
PPB in childhood is very rare. Our patient, as most of
those reported in the literature 5 8 , presented unspecific
respiratory symptoms; the x-ray revealed a large intrathoracic
mass, suggesting the need for further imaging
studies. It is important to emphasize the role of an
early imaging examination (x-ray, ultrasound scan, CT
or MRI) to detect as soon as possible the mass, in order
to proceed to more specific investigations to elucidate
the nature and staging of this malignant tumour. Radiographic
findings of pleuropulmonary blastoma are not
specific, especially when most of the neoplasm is cystic,
resembling the radiographic features of teratoma.
In this respect we note that PPB may initially manifest
with clinical and radiologie signs and symptoms of
pneumothorax 5 and may arise from other dysplastic
conditions; as a matter of fact, cystic pulmonary adenomatoid
malformation (CPAM) can be associated
with PPB, which is also described in association with
some congenital dysembriogenic abnormalities as cystic
nephroma 3 . The clinical and radiological presentation
in our patient showed mediastinal involvement;
the mass was not excisable at the first surgical look because
the neoplasm involved the pleura and was very
large. The histopathologic diagnosis was consistent
with type II PPB.
The features described usually correlate with a poor
prognosis 6 8 . The patient was submitted to intensive
multiagent neoadiuvant chemotherapy, which reduced
the tumour mass, making the complete surgical resection
feasible, and allowing eradication of the malignancy.
Such intensive multiagent chemotherapy is in most cases
necessary for the reduction and complete excision of
the tumor, which represents the most favourable factor
for long term survival.
In a recent report describing 11 patients 7 , two underwent
total excision of the tumour at diagnosis, and
were both alive without disease at 23 and 132 months
respectively, with no adjuvant chemotherapy administered
in the latter; another 3 patients remained disease
free, two after macroscopic total resection and polychemotherapy
and one after polychemotherapy and delayed
complete surgery.
The effectiveness of chemotherapy has also been reported
by other Authors 8 1\ub0. The choice of the antiblastic
agents used in our patients was due to their known
effectiveness on mesenchymal and epithelial tumors n.
Our patient was not treated with radiotherapy, which
has proven to be effective in few patients 1.
In conclusion, this case suggests that PPB may be taken
in consideration for the differential diagnosis in respiratory
distress. According to our experience and to
other literature reports, total remission of this condition
may be achieved with complete surgical excision (primary
or delayed) and intensive chemotherapy.
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