Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells. METHODS: Children with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually. RESULTS: Between 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n = 8) or regrowth of type I PPB at the surgical site (n = 3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB. CONCLUSIONS: For young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

Outcomes for Children With Type II and Type III Pleuropulmonary Blastoma Following Chemotherapy: A Report From the International PPB/DICER1 Registry.

PURPOSE: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis. METHODS: Patients with known or suspected PPB were enrolled in the International PPB/DICER1 Registry. Medical records were abstracted with follow-up ascertained annually. All PPB diagnoses were confirmed by central pathology review. Beginning in 2007, the IVADo regimen (ifosfamide, vincristine, actinomycin-D, and doxorubicin) was recommended as a potential treatment regimen for children with type II and type III PPB. This regimen was compared with a historical control cohort. RESULTS: From 1987 to 2021, 314 children with centrally confirmed type II and type III PPB who received upfront chemotherapy were enrolled; 132 children (75 with type II and 57 with type III) received IVADo chemotherapy. Adjusted analyses suggest improved overall survival for children treated with IVADo in comparison with historical controls with an estimated hazard ratio of 0.65 (95% CI, 0.39 to 1.08). Compared with localized disease, distant metastasis at diagnosis was associated with worse PPB event-free survival and overall survival with hazard ratio of 4.23 (95% CI, 2.42 to 7.38) and 4.69 (95% CI, 2.50 to 8.80), respectively. CONCLUSION: The use of IVADo in children with type II and type III PPB resulted in similar-to-improved outcomes compared with historical controls. Inferior outcomes with metastatic disease suggest the need for novel therapies. This large cohort of uniformly treated children with advanced PPB serves as a benchmark for future multicenter therapeutic studies for this rare pediatric tumor.

Pulmonary blastoma in a pregnant woman: a case report and brief review of the literature.

BACKGROUND: Pulmonary blastoma (PB) comprises a rare heterogeneous group of lung tumours typically containing immature epithelial and mesenchymal structures that imitate the embryonic lung tissue and extremely rarely occurs during pregnancy. Although cough and haemoptysis are the most common PB symptoms, they usually indicate other serious pregnancy-related complications. CASE PRESENTATION: The article presents the unusual case of a 22-year-old pregnant woman diagnosed with PB during pregnancy. CONCLUSIONS: PB is characterized by poor prognosis and patients' outcome relies on a rapid diagnosis. Surgery remains the most common and effective treatment. Due to the extreme rarity, the literature contains only single mentions of PB in pregnancy, thus its impact on the course of pregnancy and the developing fetus remains unknown.

Intraventricular topotecan in the successful treatment of recurrent CNS pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare pediatric tumor of the pleura and pulmonary mesenchyme, associated with pathogenic germline DICER1 mutations. Although the most common site of metastasis is the central nervous system (CNS), patients with CNS metastasis have dismal outcome. We report a case of a patient presenting with type II PPB and intracranial and bone metastases. We describe a multimodal therapy approach and highlight the use of intraventricular topotecan for isolated CNS recurrence. In addition, a new pathogenic germline mutation heterozygous for the c.1234delT of DICER1 was identified. Patient remains in remission 3 years after recurrence.

Thoracic Sertoli-Leydig cell tumor: An alternative type of pleuropulmonary blastoma associated with DICER1 variation.

A 2-year-old boy presented with a large cystic and solid chest mass arising from the lung, radiographically consistent with pleuropulmonary blastoma (PPB). He underwent right lower lobectomy with resection of a well-circumscribed, mixed solid and cystic mass. The solid areas were composed of cords and nests of tumor cells in the myxoid stroma and retiform foci whose pathologic and immunophenotypic findings were consistent with a sex cord-stromal tumor with features of a Sertoli-Leydig cell tumor. Tumor testing showed a pathogenic variant in the DICER1 RNase IIIb hotspot domain. Family history was suggestive of DICER1 germline pathogenic DICER1 variation in absence of a detectable germline variant. He received 12 cycles of chemotherapy with ifosfamide, vincristine, dactinomycin and doxorubicin (IVADo) and surgery with complete response. One year after completion of chemotherapy, imaging studies showed concern for recurrence confirmed by thorascopic biopsy of a pleural-based mass. He is currently receiving cisplatin-based chemotherapy with reduction in tumor size. Review of the literature showed no similar cases; however, review of our pathology files revealed a single similar case of anterior mediastinal Sertoli cell tumor in a 3-year-old girl.

Classic biphasic pulmonary blastoma: a case report and review of the literature.

Pulmonary blastoma (PB) is a very rare malignant lung tumor consisting of classic biphasic PB, well-differentiated fetal adenocarcinoma, and pleuropulmonary blastoma. We herein present an unusual case involving a patient with classic biphasic PB who underwent right upper lobe resection and subsequent treatment. No standard treatment guidelines are available for PB because of its rarity. Our patient received nedaplatin plus paclitaxel as adjuvant chemotherapy. After disease recurrence, the patient received two cycles of etoposide-cisplatin and six cycles of pemetrexed, bevacizumab, and carboplatin. Because of severe adverse effects of the chemotherapy, the patient was finally administered anlotinib, a new oral multikinase inhibitor. Both the tumor size and the serum tumor marker concentration decreased. In conclusion, surgical excision is the treatment of choice for PB. Chemotherapy in the present case resulted in PB activity that was consistent with the literature. Targeted therapies including antiangiogenic agents should be considered as a new treatment option for this rare disease.

ADVL1522: A phase 2 study of lorvotuzumab mertansine (IMGN901) in children with relapsed or refractory wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor, or synovial sarcoma-A Children's Oncology Group study.

BACKGROUND: Lorvotuzumab mertansine (IMGN901) is an antibody-drug conjugate linking an antimitotic agent (DM1) to an anti-CD56 antibody (lorvotuzumab). Preclinical efficacy has been noted in Wilms tumor, rhabdomyosarcoma, and neuroblastoma. Synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), and pleuropulmonary blastoma also express CD56. A phase 2 trial of lorvotuzumab mertansine was conducted to assess its efficacy, recommended phase 2 dose, and toxicities. METHODS: Eligible patients had relapsed after or progressed on standard therapy for their tumor type. Lorvotuzumab mertansine (110 mg/m2 per dose) was administered at the adult recommended phase 2 dose intravenously on days 1 and 8 of 21-day cycles. Dexamethasone premedication was used. Pharmacokinetic samples, peripheral blood CD56-positive cell counts, and tumor CD56 expression were assessed. RESULTS: Sixty-two patients enrolled. The median age was 14.3 years (range, 2.8-29.9 years); 35 were male. Diagnoses included Wilms tumor (n = 17), rhabdomyosarcoma (n = 17), neuroblastoma (n = 12), synovial sarcoma (n = 10), MPNST (n = 5), and pleuropulmonary blastoma (n = 1). Five patients experienced 9 dose-limiting toxicities: hyperglycemia (n = 1), colonic fistula (n = 1) with perforation (n = 1), nausea (n = 1) with vomiting (n = 1), increased alanine aminotransferase in cycle 1 (n = 2), and increased alanine aminotransferase in cycle 2 (n = 1) with increased aspartate aminotransferase (n = 1). Non-dose-limiting toxicities (grade 3 or higher) attributed to lorvotuzumab mertansine were rare. The median values of the maximum concentration, half-life, and area under the curve from zero to infinity for DM1 were 0.87 µg/mL, 35 hours, and 27.9 µg/mL h, respectively. Peripheral blood CD56+ leukocytes decreased by 71.9% on day 8. One patient with rhabdomyosarcoma had a partial response, and 1 patient with synovial sarcoma achieved a delayed complete response. CONCLUSIONS: Lorvotuzumab mertansine (110 mg/m2 ) is tolerated in children at the adult recommended phase 2 dose; clinical activity is limited.

[Clinicopathologic features and prognosis of 28 cases of pleuralpulmonary blastoma in children].

Objective: To explore the clinical characteristics, therapeutic methods and prognosis of pleuropulmonary blastoma in children. Methods: The clinical data of 28 patients with pleuropulmonary blastoma diagnosed in Guangzhou Women and Children's Medical Centre from November 2008 to May 2018 were collected and retrospectively analyzed. Results: Of the 28 patients, 18 were male and 10 were female, aged from 22 days to 5 years 10 month, the average age was 2 years 6 months. One patient underwent biopsy and other 27 underwent operation, 14 patients with type Ⅱ/Ⅲ pleuropulmonary blastoma received postoperative chemotherapy. Five patients were pathologically diagnosed as typeⅠpleuropulmonary blastoma, 5 were type Ⅱ pleuropulmonary blastoma and 18 were type Ⅲ pleuropulmonary blastoma. During the follow-up period of 24 patients, 15 patients were disease free survival, 3 patients relapsed within 6 months, 10 months and 18 months after chemotherapy, respectively. One patient who received postoperative chemotherapy suffered a bone metastasis within 11 months, 2 patient without chemotherapy relapsed within 2 months and suffered bone or renal metastasis within 3 months, respectively. Three patients who left hospital voluntarily died within 1 month. Conclusions: Pleuropulmonary blastoma is a highly malignant and rapidly progressed neoplasm. Patients with type Ⅰ pleuropulmonary blastoma have good prognoses while the prognoses of Ⅱ/Ⅲ pleuropulmonary blastoma are poor. Postoperative chemotherapy seems to improve the survival of patients withⅡ/Ⅲ pleuropulmonary blastoma.

Endobronchial pulmonary blastoma - an unusual presentation of a rare lung malignancy and review of literature.

Biphasic pulmonary blastoma (BPB) is an extremely rare highly aggressive malignant tumor that arises from fetal lung tissue and has the classical biphasic histology of epithelial and mesenchymal components. It is usually seen in adults with a slight male predominance and smokers. Previously grouped along with well-differentiated fetal adenocarcinoma (WDFA), and pleuropulmonary blastoma (PPB), now it is considered a separate variant and grouped under sarcomatoid neoplasms. Symptoms include chest pain, cough, hemoptysis and it is asymptomatic in at least one-third of the cases. A biopsy is essential for diagnosis and surgical excision is the treatment of choice. Prognosis is poor with 5-year survival less than 20% and recurrence occurring within 12 months of surgery. An aggressive multimodality approach is required for its management and active follow up surveillance is needed to look for recurrence.

Pleuropulmonary blastoma: a report from the TREP (Tumori Rari in Età Pediatrica) Project.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare, aggressive mesenchymal tumor of childhood. The Italian Tumori Rari in Età Pediatrica (TREP) Registry was the first in Europe dedicated to prospective data collection on rare pediatric tumors. We analyzed data from an Italian series of patients with PPB, focusing on the role of the TREP Project. METHODS: We considered patients aged 0-14 with histologically confirmed diagnosis, registered in population-based cancer registries (before 2000) or the TREP Registry (2000 to 2014), and analyzed data on clinical characteristics, treatment, and outcome. Event-free survival (EFS) and overall survival (OS) were estimated. Relevant prognostic factors were identified performing a univariate analysis. RESULTS: Thirty-seven cases were included (7 type I, 13 type II, 17 type III). The average diagnosis rate rose from 1.10 to 1.73 cases/year after the TREP Project started. All patients underwent surgery, 33 received chemotherapy, and 9 had radiotherapy. The median follow-up was 8.7 years. For type I, II, and III, respectively, the 5-year OS was 85.7% (33.4-97.9), 52.7% (23.4-75.5), and 57.8% (31.1-77.3); the 5-year EFS was 85.7% (33.4-97.9), 52.7% (23.4-75.5), and 52.9% (27.6-73.0). Favorable prognostic factors for EFS were Intergroup Rhabdomyosarcoma Study (IRS) stage I (p = 0.03) and T1 tumor (p = 0.05). A total of 78.3% of patients who had chemotherapy after 2000 received a standardized treatment. CONCLUSIONS: The TREP Registry showed an excellent capacity for registering cases of PPB. Patients received homogeneous treatment after the TREP Project started. Long-term outcomes were excellent for type I and unsatisfactory for type II and III. Tumor invasiveness and IRS stage were of prognostic value.

Type I pleuropulmonary blastoma presenting as congenital pulmonary airway malformation: A report of two cases.

Pleuropulmonary blastoma (PPB) is a rare aggressive intrathoracic tumor which is believed to originate from embryonic uncommitted lung mesenchymal cells, which are important for developing the lung. Type I PPB is cystic, type II is cystic and solid, while type III is predominantly solid. Diagnosing type 1 PPB is a challenge for both radiologists as well as pathologists. Owing to its purely cystic nature, type I PPB it is often mistaken for unrelated entities such as congenital pulmonary airway malformation and congenital lobar emphysema which delays surgical intervention. Here, we report two such cases presenting clinically and radiologically as congenital pulmonary airway malformation. On histology, a final diagnosis of type I pleuropulmonay blastoma was made. Thereafter, chemotherapy was administered following complete surgical excision.

Classic biphasic pulmonary blastoma: A case report and review of the literature.

Pulmonary blastomas represent about 0.5% of primary pulmonary malignancies. The prognosis is poor. Standard treatment consists of surgical excision. There are no published series on which to judge the efficacy of chemotherapy or radiation therapy. We describe an unusual case of classic biphasic pulmonary blastoma (CBPC), with long-term survival despite numerous and varied cancer-related events and review the literature. Our 71-year-old Caucasian woman presented with history of blood in sputum in 2009. Right lower lobectomy yielded a diagnosis of sarcomatoid carcinoma (pneumoblastoma). Unusually, our patient is still alive 7 years after initial surgery, despite metastatic first relapse after 2 years. Metastatic progression was confirmed histologically on three separate occasions during the disease course. The patient received a combination of cisplatin (or carboplatin) and etoposide on three separate occasions. Molecular biology studies of CBPC are needed to identify effective treatments, and a patient registry should be created.

ROS1 Rearrangement in a Case of Classic Biphasic Pulmonary Blastoma.

Classic biphasic pulmonary blastoma (CBPB) is a rare and aggressive type of non-small cell lung carcinoma (NSCLC) presenting in adults in the fourth to fifth decade. The prognosis is poor and after surgical resection, therapeutic options are often limited. ROS1 is a proto-oncogene receptor tyrosine kinase that has been identified in some types of NSCLC. We report a case of a 36-year-old woman with CBPB, which was subsequently found to have a ROS1 rearrangement. This is the first reported case of a ROS1-rearranged CBPB. This finding has therapeutic implications as these tumors have the potential to be treated with receptor tyrosine kinase inhibitors.

Type III pleuropulmonary blastoma in a dicer1 germline mutation carrier: The management of residual lung cystic lesions.

Pleuropulmonary blastoma (PPB) is a rare malignancy of childhood. It often represents a manifestation of a hereditary tumor predisposition syndrome (DICER1 syndrome). Because of its malignant potential, surgical resection of cystic lung lesions is recommended in germline DICER1 mutation carriers. We present a case of a 3-year-old male child with type III PPB successfully managed with ifosfamide, vincristine, actinomycin-D, and doxorubicin (IVADo) chemotherapy and surgery. A heterozygous germline pR688X mutation of DICER1 gene was demonstrated. Six years after primary diagnosis, several small lung cysts remained stable without further therapy. The management of residual asymptomatic lung cysts represents a clinical challenge in these patients.

Unresectable Middle Mediastinal Biphasic Pulmonary Blastoma.

We report a case of a young male who presented with an unresectable, centrally-located classic biphasic pulmonary blastoma (CBPB) involving his bilateral mainstem bronchi and esophagus and a synchronous right testicular seminoma. CBPB is a rare and aggressive tumor that most commonly presents as a solitary mass in the periphery of the lung. Surgical resection is the preferred treatment for CBPB, as chemotherapy and radiation have demonstrated limited effectiveness. In the current case, four cycles of cisplatin, ifosfamide, and etoposide with concurrent radiotherapy resulted in a favorable response at three months. Currently he optimal treatment for unresectable pulmonary blastomas remains undefined.

Pleuropulmonary blastoma type III extended into the left atrium in a 16-month old boy.

Pleuropulmonary blastoma is an uncommon paediatric neoplasm. Approximately 300 cases have been reported. In seven tumours, extension involved the left heart. Type III occurs typically at ages 3 or 4 years. We report this very unusual case of extensive disease in a 16-month old male patient. Chest computerized tomography revealed a mass extending into the right hemithorax from the posterior mediastinum and propagating inside the left atrium through the right pulmonary veins. Echocardiography showed a huge flexible mass occupying almost all of the left atrium cavity and intermittently prolapsing through the mitral valve. Two preoperative chemotherapy courses of ifosfamide, vincristine, actinomycin D and doxorubicin were administered at 3-week intervals. The patient was placed on cardiopulmonary bypass, cardiac arrest and the left atrium was opened. The tumour and orifice of the inferior right pulmonary vein were resected and the normal free borders reconstructed. A large mass occupying the right pleural space was removed. Seven additional courses of chemotherapy were given. In a 'second-look' surgery 6 months later, through a right thoracotomy, the residual mass at the posterior mediastinum was resected. The child received four additional courses of chemotherapy. After 12 months of the initial resection, there is no evidence of recurrence.

Thoracoscopic lobectomy for type I pleuropulmonary blastoma in an infant.

Pleuropulmonary blastoma (PPB) is a rare, aggressive, intrathoracic mesenchymal neoplasm associated with cystic lung lesions. The authors describe an 8-month-old male who underwent thoracoscopic left upper lobectomy for a cystic lung lesion initially diagnosed as congenital pulmonary airway malformation. Pathology revealed type I PPB.

A rare occurrence of biphasic pulmonary blastoma in an elderly male.

Pulmonary Blastoma (PB) is a rare primary lung malignancy usually occurring in young to middle aged adults. Surgery is the primary mode of treatment, but survival is poor with the mean 5-year survival being approximately 16%. We report on a case of PB arising in a 63-year-old man. Computed tomography, magnetic resonance imaging and positron emission tomography confirmed the mass to be of pulmonary origin. The morphological appearance combined with the immunoprofile of the tumour was consistent with a poorly-differentiated biphasic pulmonary blastoma. Two months after the surgical resection the patient relapsed with multiple sites of metastasis. The patient was treated with four cycles of cyclophosphamide-, doxorubicin- and vincristine-(CAV)-based chemotherapy, achieving a partial response to treatment. He is currently on a two-monthly review and is recovering from chemotherapy-related toxicities.

Primary pulmonary blastoma of monophasic variety--diagnosis and management.

Pulmonary blastoma is a rare primary lung neoplasm, in that monophasic variety is far too rare. There are no specific clinical features seen for pulmonary blastoma; computed tomography and histopathology are diagnostic. Surgical excision is the treatment of choice; however, adjuvant chemotherapy and radiotherapy may be required in large and aggressive tumors.