Desafios com Cistos Pulmonares Congénitos: Quando Considerar o Teste DICER1? Uma Revisão Narrativa
DOI:
https://doi.org/10.20344/amp.23967Palavras-chave:
Blastoma Pulmonar/genética, Criança, Malformação Adenomatoide Quística Congénita do Pulmão, Mutação em Linhagem Germinativa, Ribonuclease III/genéticaResumo
As malformações congénitas das vias aéreas pulmonares (MCVAP), segundo a classificação de Stocker, são representadas por cinco tipos, dos quais dois são de natureza não cística (tipos 0 e 3), enquanto os restantes apresentam-se como lesões pulmonares císticas (tipos 1, 2 e 4). Embora exista consenso quanto à abordagem cirúrgica das lesões sintomáticas, os casos assintomáticos colocam maiores dificuldades no que diz respeito à intervenção terapêutica. O dilema torna-se ainda mais complexo com as MCVAP tipos 1 e 4, devido ao seu potencial preneoplásico. No caso da MCVAP tipo 1, há relatos de adenocarcinoma lipídico originado a partir do componente mucinoso. A MCVAP tipo 4 foi equiparada ao blastoma pleuropulmonar (BPP) quístico ou tipo I, uma hipótese que já foi contestada no passado. O BPP está associado a variantes heterozigóticas germinativas ou somáticas no gene DICER1. Foi reconhecido que o estadio mais precoce da progressão sarcomatosa do BPP corresponde a uma lesão multicística localizada na periferia do pulmão, cujas características arquitectónicas são idênticas às da MCVAP tipo 4. Esta revisão narrativa aborda aspetos-chave das questões patogenéticas e de diagnóstico do BPP tipo I/MCVAP tipo 4, bem como a associação entre DICER1 e BPP, oferecendo informações valiosas para especialistas em pediatria e clínicos que acompanham jovens adultos afetados pela presença de variantes germinativas no gene DICER1.
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Referências
Pederiva F, Rothenberg SS, Hall N, Ijsselstijn H, Wong KK, von der Thüsen J, et al. Congenital lung malformations. Nat Rev Dis Primers. 2023;9:60.
Priest JR, Williams GM, Hill DA, Dehner LP, Jaffé A. Pulmonary cysts in early childhood and the risk of malignancy. Pediatr Pulmonol. 2009;44:14-30.
Gornall AS, Budd JL, Draper ES, Konje JC, Kurinczuk JJ. Congenital cystic adenomatoid malformation: accuracy of prenatal diagnosis, prevalence and outcome in a general population. Prenat Diagn. 2003;23:997-1002.
Mon RA, Johnson KN, Ladino-Torres M, Heider A, Mychaliska GB, Treadwell MC, et al. Diagnostic accuracy of imaging studies in congenital lung malformations. Arch Dis Child Fetal Neonatal Ed. 2019;104:F372-7.
Sintim-Damoa A, Cohen HL. Fetal imaging of congenital lung lesions with postnatal correlation. Pediatr Radiol. 2022;52:1921-34.
Adams NC, Victoria T, Oliver ER, Moldenhauer JS, Adzick NS, Colleran GC. Fetal ultrasound and magnetic resonance imaging: a primer on how to interpret prenatal lung lesions. Pediatr Radiol. 2020;50:1839-54.
Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol. 1977;8:155-71.
Stocker JT. Cystic lung disease in infants and children. Fetal Pediatr Pathol. 2009;28:155-84.
Stocker JT. Congenital pulmonary airway malformation: a new name for and an expanded classification of congenital cystic adenomatoid malformation of the lung. Histopathology. 2002;41:S424-30.
van Koningsbruggen S, Ahrens F, Brockmann M, Michalk D, Rietschel E. Congenital cystic adenomatoid malformation type 4. Pediatr Pulmonol. 2001;32:471-5.
Brcic L, Fakler F, Eidenhammer S, Thueringer A, Kashofer K, Kulka J, et al. Pleuropulmonary blastoma type I might arise in congenital pulmonary airway malformation type 4 by acquiring a Dicer 1 mutation. Virchows Arch. 2020;477:375-82.
Hill DA, Jarzembowski JA, Priest JR, Williams G, Schoettler P, Dehner LP. Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol. 2008;32:282-95.
Pio L, Gentilino V, Macchini F, Scarpa AA, Lo Piccolo R, Conforti A, et al. Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery. Pediatr Surg Int. 2024;40:53.
Kersten CM, Hermelijn SM, Mullassery D, Muthialu N, Cobanoglu N, Gartner S, et al. The management of asymptomatic congenital pulmonary airway malformation: results of a European delphi survey. Children. 2022;9:1153.
Leblanc C, Baron M, Desselas E, Phan MH, Rybak A, Thouvenin G, et al. Congenital pulmonary airway malformations: state-of-the-art review for pediatrician’s use. Eur J Pediatr. 2017;176:1559-71.
Morini F, Zani A, Conforti A, van Heurn E, Eaton S, Puri P, et al. Current management of congenital pulmonary airway malformations: a “European Pediatric Surgeons’ Association” survey. Eur J Pediatr Surg. 2018;28:1-5. Erratum in: Eur J Pediatr Surg. 2018;28:e1.
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009;325:965.
Nelson AT, Harris AK, Watson D, Miniati D, Finch M, Kamihara J, et al. Type I and Ir pleuropulmonary blastoma (PPB): a report from the International PPB/DICER1 registry. Cancer. 2023;129:600-13.
Schultz KA, Harris AK, Nelson AT, Watson D, Lucas JT Jr, Miniati D, et al. Outcomes for children with type ii and type III pleuropulmonary blastoma following chemotherapy: a report from the international PPB/DICER1 registry. J Clin Oncol. 2023;41:778-89.
Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, et al. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011;48:273-8.
Dehner LP, Messinger YH, Schultz KA, Williams GM, Wikenheiser-Brokamp K, Hill DA. Pleuropulmonary blastoma: evolution of an entity as an entry into a familial tumor predisposition syndrome. Pediatr Dev Pathol. 2015;18:504-11.
Schultz KA, Williams GM, Kamihara J, Stewart DR, Harris AK, Bauer AJ, et al. DICER1 and associated conditions: identification of at-risk individuals and recommended surveillance strategies. Clin Cancer Res. 2018;24:2251-61.
González IA, Stewart DR, Schultz KA, Field AP, Hill DA, Dehner LP. DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol. 2022;35:4-22.
Priest JR, McDermott MB, Bhatia S, Watterson J, Manivel JC, Dehner LP. Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer. 1997;80:147-61.
Manivel JC, Priest JR, Watterson J, Steiner M, Woods WG, Wick MR, et al. Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood. Cancer. 1988;62:1516-26.
Ueda K, Gruppo R, Unger F, Martin L, Bove K. Rhabdomyosarcoma of lung arising in congenital cystic adenomatoid malformation. Cancer. 1977;40:383-8.
Vargas SO, Korpershoek E, Kozakewich HP, de Krijger RR, Fletcher JA, Perez-Atayde AR. Cytogenetic and p53 profiles in congenital cystic adenomatoid malformation: insights into its relationship with pleuropulmonary blastoma. Pediatr Dev Pathol. 2006;9:190-5.
Libretti L, Ciriaco P, Casiraghi M, Arrigoni G, Zannini P. Pleuropulmonary blastoma in the area of a diagnosed congenital lung cyst. Ann Thorac Surg. 2008;85:658-60.
Nasr A, Himidan S, Pastor AC, Taylor G, Kim PC. Is congenital cystic adenomatoid malformation a premalignant lesion for pleuropulmonary blastoma? J Pediatr Surg. 2010;45:1086-9.
Ghosh M, Islam N, Ghosh A, Chaudhuri PM, Saha K, Chatterjee U. Pleuropulmonary blastoma developing in a case of misinterpreted congenital pulmonary airway malformation: a case report. Fetal Pediatr Pathol. 2018;37:377-86.
Dehner LP, Schultz KA, Hill DA. Congenital pulmonary airway malformations with a reconsideration and current perspective on the stocker classification. Pediatr Dev Pathol. 2023;26:241-9.
Priest JR. Pleuropulmonary blastoma. In: Rare tumors in children and adolescents; Schneider DT, Brecht IB, Olson THA, Ferrari A, editors. Berlin/Heidelberg: Springer; 2012. p. 213-21.
Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, et al. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer. 2015;121:276-85.
Nelson AT, Chen KS, Schultz KA. Pleuropulmonary blastoma and DICER1-related tumor predisposition: from clinicopathologic observations to clinical trial. Curr Opin Pediatr. 2025;37:48-55.
Sauvat F, Michel JL, Benachi A, Emond S, Revillon Y. Management of asymptomatic neonatal cystic adenomatoid malformations. J Pediatr Surg. 2003;38:548-52.
Ruchonnet-Metrailler I, Leroy-Terquem E, Stirnemann J, Cros P, Ducoin H, Hadchouel A, et al. Neonatal outcomes of prenatally diagnosed congenital pulmonary malformations. Pediatrics. 2014;133:e1285-91.
Karlsson M, Conner P, Ehren H, Bitkover C, Burgos CM. The natural history of prenatally diagnosed congenital pulmonary airway malformations and bronchopulmonary sequestrations. J Pediatr Surg. 2022;57:282-7.
Zirpoli S, Munari AM, Primolevo A, Scarabello M, Costanzo S, Farolfi A, et al. Agreement between magnetic resonance imaging and computed tomography in the postnatal evaluation of congenital lung malformations: a pilot study. Eur Radiol. 2019;29:4544-54.
Bolde S, Pudale S, Pandit G, Ruikar K, Ingle SB. Congenital pulmonary airway malformation: a report of two cases. World J Clin Cases. 2015;3:470-3.
Wu H, Tian J, Li H, Lu L, Chen X, Xu W. Computed tomography features can distinguish type 4 congenital pulmonary airway malformation from other cystic congenital pulmonary airway malformations. Eur J Radiol. 2020;126:108964.
Feinberg A, Hall NJ, Williams GM, Schultz KA, Miniati D, Hill DA, et al. Can congenital pulmonary airway malformation be distinguished from type I pleuropulmonary blastoma based on clinical and radiological features? J Pediatr Surg. 2016;51:33-7.
Schultz KA, Stewart DR, Kamihara J, Bauer AJ, Merideth MA, Stratton P, et al. DICER1 tumor predisposition.. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews®. Seattle: University of Washington; 2020.
Capozzi A, Jansen FA, Smetsers SE, Bakhuizen JJ, Hiemcke-Jiwa LS, Kranendonk ME, et al. The histological spectrum of DICER1-associated neoplasms. Pediatr Dev Pathol. 2025;28:231-43.
Foulkes WD, Priest JR, Duchaine TF. DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer. 2014;14:662-72.
Jansen FA, Bakhuizen J, Kester L, de Krijger RR. DICER1 syndrome: what do we know of the pathogenetic mechanisms? Cancers. 2025;17:2885.
Schultz KA, Harris AK, Finch M, Dehner LP, Brown JB, Gershenson DM, et al. DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry. Gynecol Oncol. 2017;147:521-7.
Apellaniz-Ruiz M, Segni M, Kettwig M, Glüer S, Pelletier D, Nguyen VH, et al. Mesenchymal hamartoma of the liver and DICER1 syndrome. N Engl J Med. 2019;380:1834-42.
Schultz KA, MacFarland SP, Perrino MR, Mitchell SG, Kamihara J, Nelson AT, et al. Update on pediatric surveillance recommendations for PTEN hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex. Clin Cancer Res. 2025;31:234-44.
Hill DA, Sadeghi S, Schultz MZ, Burr JS, Dehner LP. Pleuropulmonary blastoma in an adult: an initial case report. Cancer. 1999;85:2368-74.
Schultz KA, Yang J, Doros L, Williams GM, Harris A, Stewart DR, et al. DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome: a unique constellation of neoplastic conditions. Pathol Case Rev. 2014;19:90-100.
Faure A, Atkinson J, Bouty A, O’Brien M, Levard G, Hutson J, et al. DICER1 pleuropulmonary blastoma familial tumour predisposition syndrome: What the paediatric urologist needs to know. J Pediatr Urol. 2016;12:5-10.
Priest JR, Watterson J, Strong L, Huff V, Woods WG, Byrd RL, et al. Pleuropulmonary blastoma: a marker for familial disease. J Pediatr. 1996;128:220-4.
Schultz KA, Nelson AT, Mallinger PH, Harris AK, Kamihara J, Baldinger S, et al. DICER1-related tumor predisposition: identification of at-risk individuals and recommended surveillance strategies. Clin Cancer Res. 2024;30:5681-92.
Sabapathy DG, Guillerman RP, Orth RC, Zhang W, Messinger Y, Foulkes W, et al. Radiographic screening of infants and young children with genetic predisposition for rare malignancies: DICER1 mutations and pleuropulmonary blastoma. AJR Am J Roentgenol. 2015;204:W475-82.
Knight S, Knight T, Khan A, Murphy AJ. Current management of pleuropulmonary blastoma: a surgical perspective. Children. 2019;6:86.
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