John R. Priest

Background: Types II and III pleuropulmonary blastoma (PPB) are aggressive sarcomas of lung and pleura in young children. Similar to cavoatrial extension of Wilms tumor, PPB may extend into thoracic great vessels and the heart and may involve both venous and arterial circulations and right and left cardiac chambers. Serious embolic complications occur.Procedure: Review International PPB Registry databases and literature (1) for PPB cases with vascular/cardiac extension and (2) for neoadjuvant chemotherapy results in vascular extension cases.Results: Among 179 Registry‐confirmed and approximately 200 literature Type II and III PPB cases, 11 examples (approximately 3%) of great vessel/cardiac extension were identified; 1 case is presented in detail. Nine cases involved the left circulation, one the right and one both. Various radiographic techniques including echography, computed tomography and gated magnetic resonance imaging identified vascular tumor. Seven children had arterial embolic events: cerebrovascular accidents (six, including one femoral artery occlusion) and acute aortic occlusion (1). Six of these seven died from complications that may be attributed to vascular involvement. In three of four children with vascular involvement, neoadjuvant chemotherapy lessened the involvement; in one the effect could not be assessed. None of these four had embolic events. Effect on survival could not be assessed due to small numbers.Conclusions: Involvement of thoracic great vessels and the heart is a serious complication of PPB, with fatal embolic complications possible. Radiographic evaluation of the central circulation should be performed in children with suspected or diagnosed PPB to identify this complication. Pediatr Blood Cancer 2011;56:604–609.

Background and aims Ciliary body medulloepithelioma (CBME) is a rare embryonal ocular tumour of children under age 10 years. Pleuropulmonary blastoma (PPB) is a rare embryonal lung tumour in young children and the sentinel disease of the PPB Family Tumour and Dysplasia Syndrome, a distinctive predisposition leading to unusual dysontogenetic-dysplastic and neoplastic conditions in PPB patients and their relatives. Germline mutations of DICER1 gene, a key regulator of gene silencing, underlie this syndrome. CBME occurs with PPB. The authors' aim was to identify CBME cases associated with PPB. Methods The authors evaluated International PPB Registry and literature PPB cases for CBME, including review of pathologic specimens. Results Four CBME were observed among 550–600 PPB cases; three in patients and one in a parent. One CBME was clinically diagnosed; three were confirmed pathologically (one benign teratoid CBME; one benign non-teratoid CBME; one case, details not available). Conclusions These observations suggest that CBME is a manifestation of the tumour predisposition associated with PPB. Paediatric oncologists and ophthalmologists should be aware that CBME can occur in PPB patients or their relatives and that CBME may indicate a hereditable tumour predisposition for a child or family.

Surgery for congenital and early childhood lung cysts is often dictated by symptoms such as respiratory distress, infection or pneumothorax. Asymptomatic cysts present a therapeutic dilemma: surgical intervention and “conservative” observation have advocates. The risk of malignancy in such cysts is considered by some an indication for surgical intervention and is reviewed in this paper. Pleuropulmonary blastoma (PPB) is the most frequent malignancy associated with childhood lung cysts. Although rare, PPB occurs predictably in certain clinical and familial situations. This unique biology of PPB can inform the cyst management decision. The earliest manifestation of PPB is a malignant lung cyst in young children, clinically and radiographically indistinguishable from benign congenital lung cysts. Histopathologic examination differentiates cystic PPB from the benign cystic variants. Surgical excision of cystic PPB (with or without chemotherapy) cures approximately 85–90% of children. If not excised, cystic PPB evolves to cystic/solid or solid high‐grade sarcoma (cure rate 45–60%) by age 2–6 years. Numerous reports of “malignancy in a congenital lung cyst” are now understood as the characteristic progression of cystic PPB. PPB is genetically determined in many cases. Detailed family history may reveal the hallmarks of PPB in the patient or young relatives: a unique constellation of diseases including lung cysts, cystic nephroma, childhood cancers, stromal sex‐chord ovarian tumors, seminomas or dysgerminomas, intestinal polyps, thyroid hyperplasias, and hamartomas. Pneumothorax and multifocal/bilateral lung cysts also characterize PPB. These diagnoses predict that a lung cyst is more likely PPB than a benign congenital cyst. Patients fitting this pattern deserve histologic diagnosis. The genetic basis for this heritable syndrome is unknown but is being actively investigated. Pediatr Pulmonol. 2009; 44:14–30.

Purpose: Type I pleuropulmonary blastoma (PPB) is a rare, cystic lung neoplasm in infants characterized by subtle malignant changes and a good prognosis. Recurrences after type I PPB are usually advanced type II or type III neoplasms with a poor prognosis. This article describes the first collection of type I PPB cases, analyzes outcome based on treatments of surgery or surgery plus chemotherapy, and presents type I PPB management recommendations. Patients and Methods: Type I PPB cases from the International PPB Registry and literature were evaluated using standard statistical methods for outcomes based on age at diagnosis, sex, thoracic side, surgical extent, length of follow-up, constitutional/familial disease, pre-existing lung cysts, intrathoracic findings, and treatments (surgery or surgery and chemotherapy). Results: Thirty-eight type I PPB cases were identified: Registry (n = 30) and literature (n = 8). Twenty children had surgery alone; eight (40%) experienced recurrence; and four died. Eighteen children had surgery and adjuvant chemotherapy; one experienced recurrence and died. All recurrences were type II or III PPB. Recurrence-free survival was higher in the surgery + chemotherapy group (P = .01); overall survival did not differ (P = .18). The improved recurrence-free survival was found only in males. Four of nine children with recurrence survived. Conclusion: Adjuvant chemotherapy appears to benefit type I PPB patients. Benefit limited to males requires broader substantiation. Salvage after types II and III recurrence is poor (four of nine; 44%). A rigorous surveillance schedule after type I PPB diagnosis might detect early recurrence and be an acceptable alternative to adjuvant chemotherapy.

Background: Pleuropulmonary blastoma (PPB) is a rare tumor of pleura and lung in young children. Central nervous system (CNS) complications, particularly cerebral parenchymal metastases, occur in aggressive forms of PPB: Types II and III PPB. This article evaluates cerebral and meningeal metastases, cerebrovascular events (CVA) caused by tumor emboli, spinal cord complications, and intracranial second malignancies in PPB.Procedure: International PPB Registry and literature cases were evaluated for CNS events. Cerebral metastasis patients were evaluated for gender, side of origin of PPB, PPB Type, interval from diagnosis to metastasis, status of chest disease, treatment, and outcome. Standard statistical methods were used to calculate the cumulative probability of cerebral metastasis and survival following metastasis.Results: Thirty‐nine cases of cerebral metastasis were identified in 5/53 Registry Type II cases, 15/44 Registry Type III cases, and 19/143 literature Type II/III cases. Metastases occurred 1–60, median 11.5 months after diagnosis. Chest disease was controlled in 50% of children at time of metastasis. The cumulative probability of cerebral metastasis by 5 years from diagnosis was 11% for Type II patients (95%CI (confidence interval): 2–20%) and 54% for Type III patients (95%CI: 31–76%). Seven children survive cerebral metastasis. Other CNS complications were post‐operative CVA (five cases), spinal cord invasion or compression (six), leptomeningeal disease (three), and second intracranial malignancies (two).Conclusions: Cerebral metastasis is more frequent in PPB than in other childhood sarcomas. Clinicians should screen for this complication. Diverse other CNS complications are less common and require careful diagnosis. Pediatr Blood Cancer 2007;49:266–273.