Type I Pleuropulmonary Blastoma Incidentally Diagnosed in an Infant with RSV Bronchiolitis

To the Editor

A 7-month-old full term female presented to an outside emergency department for evaluation of 7 days of new-onset nasal congestion, cough, and respiratory distress. Viral nasopharynx PCR was positive for respiratory syncytial virus. A chest x-ray (CXR) showed a large gas filled space in the left upper lobe consisting of several cystic spaces or one large cyst with septations and contralateral mediastinal shift (Image 1). She was discharged home on albuterol and seen in our pediatric pulmonology clinic the following day. Parents denied a history of chronic respiratory symptoms including cough, tachypnea, respiratory distress, wheezing or recurrent respiratory infections. On physical exam she was well appearing with normal vital signs, mild subcostal retractions and diffuse rhonchi. A chest-CT with contrast was performed which showed a large cystic mass (9.9×5.5×10.1cm) in the left hemithorax compressing the left lower lobe (LLL), with mediastinal shift and right lung atelectasis (Image 2). Findings were thought to be most consistent with a Type I Congenital Pulmonary Adenomatous Malformation (CPAM). The patient was scheduled for lesion resection 4 weeks later. She underwent left upper lobectomy with no perioperative complications. Postoperative CXR revealed re-expansion of the LLL (Image 3). Pathology revealed a cystic lesion with variably sized cysts, with focal increased cellularity, scattered atypical cells with spindle shaped nuclei and hyperchromatism within the cyst septa (Image 4), consistent with a type I pleuropulmonary blastoma (PPB). The patient subsequently underwent genetic testing which revealed a mutation in the DICER1 gene.

Image 1:

AP and lateral chest xray on the day of presentation showing a large lesion in the left upper lobe consisting of several cystic spaces or one large cyst with septations leading to contralateral mediastinal shift.

Image 2:

Chest CT on the day of presentation showing a large cystic mass in the left hemithorax with few thin internal septations with resultant compression of the left lower lobe, contralateral mediastinal shift and right lung atelectasis.

Image 3:

AP chest xray post resection showing re-expansion of the left lower lobe.

Image 4:

Pathology slides showing a large cystic lesion with septa on low power field and atypical cells, spindle shaped nuclei and hyperchromatism within the cyst septa on high power field.

Although rare, PPB is the most common primary lung malignancy in childhood. PPB typically presents in early childhood with 90% of cases occurring prior to 2-years-of-age.¹ PPBs are classified based on macroscopic appearance into three categories which represent a developmental continuum: type I is cystic, type II has both solid and cystic components and type III is solid.² Type I lesions have the best prognosis with >90% survival rate.² Type II and III lesions are considered aggressive tumors as their solid components contain high-grade sarcoma elements, but multimodality treatment initiatives have improved survival rates to >70% in type II and >50% in type III.² There is also some thought that rather than being a denovo tumor, PPB can develop from benign CPAMs. Approximately 66% of PPBs are associated with germline mutations in the DICER1 gene.³ DICER1 gene mutations are also associated with other malignancies including Wilm’s tumor, thyroid cancer, ovarian tumors and embryonal rhabdomyosarcomas.¹ As demonstrated in our patient, diagnosing PPB based on symptoms and imaging is difficult as their presentation and imaging findings can overlap with benign pulmonary lesions such as CPAMs, bronchogenic cysts and congenital lobar emphysema.⁴ Recent evidence suggests that chest CT is only 33.3% sensitive in predicting malignancy in postnatally diagnosed lesions.⁴ Surgical resection is the unequivocal treatment for symptomatic lung masses, but the role of resection in asymptomatic children remains less conclusive and non-operative strategies are sometimes employed.

In summary, PPB, although rare, is the most common primary lung malignancy in children. Early diagnosis and treatment is important in preventing disease progression to a higher-grade lesion. Given its association with the DICER1 cancer predisposition syndrome, children with PPB should undergo DICER1 mutation testing so the appropriate malignancy screening protocols can be instituted. Diagnosing PPB based on symptoms and imaging is challenging as children are often asymptomatic or present with non-specific symptoms, and chest CT is not highly sensitive for predicting malignant lesions. Due to the absence of distinguishing clinical or radiographic features, risk for disease progression and association with the DICER1 cancer predisposition syndrome, it is important to consider PPB in the differential diagnosis for children with cystic lung lesions.