Pleuropulmonary Blastoma Research Articles

Therapy-related myeloid leukemia following Pleuropulmonary blastoma: A case report

The development of secondary malignancy (SM) is the most worrisome long-term complication of childhood cancer. Acute myeloid leukemia is the most prevalent neoplasm that occurs after treatment with alkylating agents and topoisomerase II inhibitors. Pleuropulmonary blastoma (PPB) is a rare lung neoplasm in children. Type II and type III of this cancer are markedly aggressive and have a recurrent nature. Chemotherapy, radiation therapy, and hematopoietic stem cell transplant (HSCT) are treatment modalities that make these patients prone to secondary malignancy. Here was presented and discussed a case of myeloid leukemia 3.5 years after treatment of Pleuropulmonary blastoma in a 5.5-year-old boy who was a candidate for high dose chemotherapy and autologous stem cells transplant (auto-SCT) because of frequent recurrence and lack of response to chemotherapy and radiation therapy. It seems this is the first reported case of therapy-related myeloid leukemia (t-AML) after PPB in children. Awareness of the creation of this complication following administration of cytotoxic therapies in the treatment of solid tumors will increase physician attention in the selection of treatment modality as well as the counseling of patients at the time of diagnosis.

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

BackgroundPulmonary 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 presentationThe article presents the unusual case of a 22-year-old pregnant woman diagnosed with PB during pregnancy.ConclusionsPB 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.

Thoracic Mass Lesions in Children and their Management: A Prospective Interventional Study

Introduction: Thoracic mass lesions in children are heterogeneous group of disorders, out of which developmental malformations such as Congenital Pulmonary Airway Malformation (CPAM), bronchogenic cysts and Congenital Lobar Emphysema (CLE) are common pathology. Primary pulmonary malignancies like carcinoid tumour and pulmonary blastoma may rarely be encountered. Aim: To analyse the clinical pattern, diagnosis and management of children with thoracic mass lesions. Materials and Methods: This prospective interventional study was conducted from June 2018 to May 2021, on 19 patients diagnosed and operated for thoracic mass lesions. It was carried out in the Department of Paediatric Surgery, Sardar Vallabhbhai Patel Post Graduate (SVP PG) Institute of Paediatrics, Srirama Chandra Bhanja (SCB) Medical College, Cuttack, Odisha, India. The final diagnosis was only based on histopathological study. The parameters assessed were demographic features, operative findings and pathological diagnosis. Statistical analysis was done using Microsoft Excel Q1 Macros software. Data was presented as mean, median with Confidence Interval (CI) and percentages (%). Results: A total number of 19 cases were operated, out of which 12 were boys and seven were girls. The median age at presentation was three month (range: five days to five years). Right side of thorax was more commonly affected in 14 cases and left side in five cases. CLE was the most common pathology (eight cases) followed by CPAM (six cases). Bronchogenic cysts and lymphangioma were detected in two cases each. Pulmonary blastoma was the only malignant lesion found. There was no mortality in the present study. Conclusion: The patients with thoracic mass lesions usually present before the age of six months and CLE was detected as the most common finding. A conclusive diagnosis can be obtained only from histopathology

Pleuropulmonary Blastoma (PPB) and Other DICER1-Associated High-Grade Malignancies are Morphologically, Genetically and Epigenetically Related – A Comparative Study of 4 PPBs and 6 Sarcomas

Pleuropulmonary Blastoma (PPB) and Other DICER1-Associated High-Grade Malignancies are Morphologically, Genetically and Epigenetically Related – A Comparative Study of 4 PPBs and 6 Sarcomas

Analysis of SMARCA4 and SMARCA2 Loss in Lung Sarcomatoid Carcinomas.

Sarcomatoid carcinomas of the lung are a group of aggressive tumors. It has been reported that losses of SMARCA4 and SMARCA2, which play a role in the repair and remodeling of chromatin, contribute to the initiation, progression, and differentiation of neoplasms. The aim of our study was to examine SMARCA4 and SMARCA2 profiles in sarcomatoid carcinomas of the lung. We screened pleomorphic carcinomas (PCs), carcinosarcomas (CSs), and pulmonary blastomas (PBs). The loss of SMARCA4 and SMARCA2 expression in the tumors was evaluated using immunohistochemical methods. The tumors were also examined to determine immunophenotype, histological tumor diagnosis, surgical resection, tumor histological component, largest tumor diameter, and lymph node metastasis status. Sixty-nine cases were screened, of which 84% were PCs, 13% were CSs, and 2.8% were PBs. In PCs components, 84.4% were biphasic and 15.5% were monophasic. The PCs showed the most frequent loss of SMARCA4 (25.8%) and SMARCA2 (44.8%). A loss of SMARCA4 and SMARCA2, respectively, was detected in 14.2% and 24.4% in both components of biphasic PCs; 12.2% and 14.2% in the sarcoma component of biphasic PCs; 0% and 8.1% in the carcinoma component of biphasic PCs; 22.2% and 33.3% in monophasic PCs; 0% and 22.2% in both components of CSs; and 0% and 22.2% in the sarcoma component of CSs. These findings demonstrate a loss of expression of SMARCA4 and SMARCA2 in pulmonary sarcomatoid carcinomas. Loss of the SMARCA complex may be caused by the heterogeneous morphological profile of sarcomatoid carcinomas, independent of tumor histopathological parameters.

Phenotypic similarities within the morphologic spectrum of DICER1-associated sarcomas and pleuropulmonary blastoma: Histopathologic features guide diagnosis in the LMIC setting.

Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differentiation. Foci of immature cartilage at diagnosis (n=2/3) and increased neuroepithelial differentiation at recurrence (n=1) were noted. Morphological suspicion prompted somatic testing at reference centers, confirming likely biallelic, loss-of-function, and "hotspot" missense DICER1 variants in all three tumors. This can serve as a model for this diagnosis in resource-limited settings and has implications for germline testing, surveillance, and tumor management.

Congenital anomalies of the large intrathoracic airways

Congenital lung lesions are numerous but rare in individual clinical practice. They do require close multidisciplinary collaboration between health care professionals. This educational review will focus on the pathophysiology, clinical manifestations, surgical approaches, and anesthetic management of congenital anomalies of the large intrathoracic airways: congenital tracheal stenosis, tracheal agenesis, tracheal diverticulum, bronchial anomalies (tracheal, esophageal, or bridging bronchus), congenital lung malformations, lung sequestrations and Scimitar syndrome, lobar emphysema, Williams-Campbell syndrome, and pleuropulmonary blastoma. In addition, this review will illustrate common pitfalls and challenges related to the anesthesia management with emphasis on ventilation and correct endotracheal tube positioning.

Клінічний випадок легеневої бластоми в дитини як маскування негоспітальної пневмонії

Currently, the problem of diagnosing pleuropulmonary blastoma in children remains relevant, because this pathology often runs under the guise of other nosologies, including pneumonia, and is extremely difficult to diagnose. Currently there are no pathognomonic clinical symptoms, specific diagnostic criteria for this disease, almost 60% of patients have nonspecific symptoms. This article presents a rare clinical case of biphasic pulmonary blastoma in a child who was examined and treated at the Ivano-Frankivsk Regional Children's Clinikal Hospital Ivano-Frankivsk Regional Council. The main clinical manifestations, diagnosis and treatment of biphasic blastoma of the lungs in a child based on the observation of a 5-year-old girl who was hospitalized for acute abdominal pain, chest pain and cough. After clinical — laboratory and instrumental methods of examination, right-sided pneumonia and exudative pleurisy were diagnosed. The set of treatment measures did not give the expected positive effect, improving the patient's condition. Additional testing is required for suspected breast cancer. It has been established that the best method for verifying the diagnosis of pulmonary blastoma is multislice computed tomography with intravenous bolus contrast and immunohistochemical examination of the biopsy. The methods of treatment used in this case, including anti-inflammatory and polychemotherapy according to the scheme, the use of radical treatment at the National Cancer Institute in Kyiv — surgery right pneumonectomy with pericardial resection. The child is currently in stable remission for 4.5 years. The described clinical case demonstrates the difficulty of diagnosing lung blastoma in children due to the lack of typical clinical manifestations. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, pneumonia, blastoma, pulmonology, diagnosis, treatment.

Surgical treatment of spontaneous pneumothorax in a patient with pleuropulmonary blastoma in a 2-year-old girl

Introduction. Pneumothorax is a life-threatening condition which may be the first manifestation of a tumor in the chest cavity in children.Material and methods. The article describes a clinical case of a two-year-old patient with spontaneous pneumothorax.Results. By literature data, pleuropulmonary blastoma is the most common malignant tumor of the thoracic cavity in young children. It is a thin-walled single or multi-cavity formation located on the lung periphery. It has a high risk of metastases, relapses as well as a tendency to higher malignancy degree. Therefore, the overall survival of patients is significantly reduced in case of late tumor detection. It is known that at early stages the structure of pleuropulmonary blastoma is similar to that of the bullous transformation in lungs, and in most cases it does not have characteristic clinical manifestations; therefore, early diagnostics of the neoplasm in case of pneumothorax depends on surgeon’s oncological alertness and on the tactics chosen by him/her to treat the complication. The performed videothoracoscopic resection of the cystic formation in the left lung did not only helped to achieve aerostasis within the short time, but it also helped to find out the cause of the complication: it was a rare malignant tumor of the lung - pleuropulmonary blastoma.Conclusion. The tumor process at the preoperative stage is difficult to suspect in children because in most cases there are no specific clinical symptoms. So, an active surgical tactics in treating cystic lung formations in patients with pneumothorax allows not only to eliminate the complication, but also to identify a malignant neoplasm at the initial stage.

Pleuropulmonary Blastoma (PPB) in Child with DICER1 Mutation: The First Case Report in the State of Qatar

Pleuropulmonary blastoma (PPB) is a rare intrathoracic malignancy, which arises from the lung parenchyma and/or pleura. PPB has strong genetic association with mutations in DICER1 gene. Despite being rare, PPB is the most common lung tumor in children below 6 years of age. International registry of the disease has a total of 350 cases worldwide. We report the first case of PPB in the state of Qatar, which presented as a large cystic lung lesion. The patient was first thought to have benign congenital pulmonary airway malformation (CPAM) based on chest X-ray findings. The diagnosis of PPB was suspected based on chest CT scan findings and was confirmed after surgical resection of the cystic mass. The case highlights the need to consider PPB in the differential diagnosis of cystic lung lesions in children and the need for further radiological imaging (i.e., CT scan), genetic testing, and/or excisional biopsy to confirm the diagnosis.

Pulmonary blastoma: a comprehensive overview of a rare entity.

Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mesenchymal component. Only a few hundred cases have been reported worldwide. The aim of this study is to review and critically assess the literature regarding pulmonary blastoma. A narrative literature review of PubMed database from the inception of the database up to January 2021, limited to the English language, was conducted, using combinations of the following keywords: "pulmonary blastoma", "biphasic pulmonary blastoma", "sarcomatoid carcinoma". Pulmonary blastoma is composed of an epithelial and a mesenchymal malignant component. Regarding pathogenesis, the origin of the biphasic cell population remains elusive. Characteristic immunohistochemical stains are supportive of diagnosis.Clinically, the symptomatology is non-specific, while 40% of the cases are asymptomatic. It is diagnosed at a younger agecompared to other types of lung cancer, and it is often non-metastatic at diagnosis allowing for surgical treatment. Data on management and survival are scarce and mainly come from isolated cases. Advances on targeted therapy may provide novel treatment options. Given the rarity of the cases, multicenter collaboration is needed in order to establish therapeutic guidelines.

PULMONARY SARCOMATOID CARCINOMA: A CASE REPORT AND REVIEW OF LITERATURE

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary sarcomatoid carcinomas are a rare subtype of poorly differentiated non-small cell lung cancer that accounts for less than 1 percent of primary lung malignancies. This case highlights the clinical presentation & diagnostic evaluation undertaken to identify this rare lung cancer. CASE PRESENTATION: A 77-year-old male with a medical history of tobacco abuse, hypertension & mutism was evaluated for pleuritic chest pain, cough and subjective fevers. Initial vitals were stable and pulmonary examination revealed focal expiratory wheezes auscultated on the right anterior chest with a prolonged expiratory phase throughout. CXR demonstrated a mass-like opacity in the inferior right hilum and the patient was treated with antibiotics for presumed community-acquired pneumonia. Chest CT was obtained due to persistent symptoms which showed a right hilar mass encasing the right pulmonary artery with calcific mediastinal lymphadenopathy. Bronchoscopy with endobronchial ultrasound was performed and samples for cytology were taken from the culprit endobronchial lesion. Lymph node surveillance revealed enlarged left paratracheal, right paratracheal & right hilar lymph nodes from which FNA samples were taken, respectively. Rapid onsite pathological evaluation demonstrated the presence of atypical cells and ultimately revealed sarcomatoid carcinoma. Oncology, radiation oncology, and palliative care were consulted. After a lengthy discussion concerning the treatment options, the patient & family elected to transition to comfort care. The patient was discharged home with hospice. DISCUSSION: Pulmonary sarcomatoid carcinoma is a rare non-small cell carcinoma accounting for approximately 0.1-0.4% of all primary pulmonary malignancies. The disease has a predilection for older males with a prolonged smoking history. Morphologically, sarcomatoid carcinoma is a heterogeneous group of neoplasms that originate from epithelial & mesenchymal tissue containing intermingled elements of carcinoma & sarcoma. There are five recognized subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma & pulmonary blastoma. Given the immense histological variability, a pathologic diagnosis frequently requires a generous tissue sample and can often pose a diagnostic challenge. The clinical course is aggressive with early metastasis rendering the overall prognosis is poor despite therapy. Surgical resection offers the best therapeutic option in early disease and remains the standard of care. Targeted therapies & immunotherapy remain a promising option, but additional research & clinical experience is needed in this patient population. CONCLUSIONS: This case highlights the clinical presentation & diagnostic evaluation undertaken to identify sarcomatoid carcinoma, a rare and aggressive lung cancer with heterogeneous pathology & limited response to traditional therapy. REFERENCE #1: Rajdev K, Siddiqui AH, Ibrahim U, Agarwal S, Ding J, Chalhoub M. Sarcomatoid Carcinoma of the Lung Presenting as Localized Bronchiectasis: A Case Report and Review of Literature. Respir Med Case Rep. 2018;24:143-146. Published 2018 May 17. doi:10.1016/j.rmcr.2018.05.016 REFERENCE #2: Shen XY, Lin ZF, Lin Q, et al. Pulmonary sarcomatoid carcinoma: a case report. Contemp Oncol (Pozn). 2013;17(2):210-213. doi:10.5114/wo.2013.34375 DISCLOSURES: No relevant relationships by Kari McCoy, source=Web Response No relevant relationships by Caroline Mears, source=Web Response No relevant relationships by Xian Qiao, source=Web Response

Likely foregut endoderm origin for a postzygotic mutation affecting the RNase IIIb domain of DICER1

In 2016, we reported a child with bilateral lung cysts and left lung type II pleuropulmonary blastoma (PPB), classic phenotypes of DICER1 syndrome; we identified a DICER1 hotspot mutation c.5425G>A,...

Children with progressive and relapsed pleuropulmonary blastoma: A European collaborative analysis

Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome. A retrospective review of children registered in national and European databases and trials (2000-2018) with diagnosis of PPB type II/III and PD or RD was performed. A total of 35 patients with PPB were analysed: patients with PD (n=9) and RD (n=26). Patients experienced PD at the median age of 3.9 years [range, 0.5-17.8] despite surgery, chemotherapy (CHT, n=9) and radiotherapy (RT, n=1) with a median time to progression of 0.58 years [range, 0.02-1.27] from diagnosis. All of them died. Patients suffered from RD at the median age of 4.3 years [1.7-15.1], median delay to relapse 1.03 years [range, 0.03-2.95]. RD occurred locally (n=12), combined (n=1) and in metastatic sites (n=13): central nervous system (n=11) and unspecified site (n=2). Patients were treated with salvage CHT (n=20), surgery (n=10)±RT (n=10). After a median follow-up of 4.2 years [range, 2.1-14.6], a second complete remission (CR) was achieved in nine out of 26 patients. Patients were alive in the second CR (n=6), in the third CR (n=1), in partial remission (n=2) and lost of follow-up (n=1). Five-year event-free survival (EFS) and overall survival (OS) for patients with RD were both 37% (±19, CI 95%). Local therapy (surgery, RT) had a favourable impact on OS (p=0.03 and 0.02, respectively). Cure of patients with RD of PPB type II/III with multimodal treatment is possible but rare. Progressive PPB is fatal and patients need new treatment options.

Unusual phenotypes in patients with a pathogenic germline variant in DICER1.

Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms' tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.

DICER1-Mutated Botryoid Fibroepithelial Polyp of the Parotid Duct: Report of the First Case

DICER1, a member of the ribonuclease III family, is involved in the biogenesis of microRNAs and, hence, it influences gene expression regulation. DICER1 germline (associated with the inherited DICER1 syndrome) or somatic mutations have been linked to tumorigenesis in histogenetically diverse benign and malignant neoplasms in different organs including pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, poorly differentiated thyroid carcinoma, thyroblastoma, intracranial sarcoma and gonadal Sertoli-Leydig cell tumors in addition to others. Moreover, rare botryoid (giant) fibroepithelial polyps may harbor this mutation. Herein, we describe the first reported case of a DICER1-mutated botryoid fibroepithelial polyp occurring within the parotid duct of a 65-year-old female who has no other features or family history of the DICER1 syndrome. Based on its distinctive morphology, we tested this lesion specifically for DICER1 mutations and confirmed the presence of a pathogenic DICER1 variant with a low allele frequency, consistent with a somatic mutation.

Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma.

Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic DICER1 variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB. Cases were collected from departmental archives and the International PPB/DICER1 Registry. Immunohistochemistry (IHC) for PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) genes were performed. In addition, normal-tumor paired whole exome sequencing (WES) was performed in two cases. Twenty-five PPB cases were studied, consisting of Type I (n = 8, including 2 Ir), Type II (n = 8) and Type III (n = 9). PD-L1 combined positive score (CPS) of 1, 4 and 80 was seen in three (3/25, 12.0%) cases of Type II PPB with negative staining in the remaining cases. PD-1 and CD8 stains demonstrated positive correlation (P < .05). The density of PD1 and CD8 in the interface area was higher than within tumor (P < .05). The MMR proteins were retained. TMB was 0.65 mutations/Mb in type II PPB with high expression of PD-L1, and 0.94 mutations/Mb in one negative PD-L1 case with metastatic tumor. A small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.

Nasal Chondromesenchymal Hamartoma in a Patient With DICER1-Predisposition Syndrome

Abstracts Nasal chondromesenchymal hamartomas (CMHs) are extremely rare tumors that are sometimes seen in patients with germline DICER1 mutations. These patients are also at increased risk of pleuropulmonary blastomas, as well as other uncommon tumors. We present the case of an 8-year-old girl with a history of pleuropulmonary blastoma who presented with worsening nasal obstruction and clinical symptoms of sinusitis secondary to a nasal CMH. The diagnosis of nasal CMH is discussed, as well as DICER1 syndrome.

Whole-Genome Methylation Study of Congenital Lung Malformations in Children.

Background and ObjectivesThe treatment of asymptomatic patients with congenital pulmonary malformations (CPMs) remains controversial, partially because the relationship between congenital lung malformations and malignancy is still undefined. Change in methylation pattern is a crucial event in human cancer, including lung cancer. We therefore studied all differentially methylated regions (DMRs) in a series of CPMs in an attempt to find methylation anomalies in genes already described in association with malignancy.MethodsThe DNA extracted from resected congenital lung malformations and control lung tissue was screened using Illumina MethylationEPIC arrays. Comparisons between the group of malformed samples or the malformed samples of same histology or each malformed sample and the controls and between a pleuropulmonary blastoma (PPB) and controls were performed. Moreover, each malformed sample was pairwise compared with its respective control. All differentially methylated regions (DMRs) with an adjusted p-value <0,05 were studied.ResultsEvery comparison highlighted a number of DMRs closed to genes involved either in cell proliferation or in embryonic development or included in the Cancer Gene Census. Their abnormal methylation had been already described in lung tumors.ConclusionsMethylation anomalies already described in lung tumors and also shared by the PPB were found in congenital lung malformations, regardless the histology. The presence of methylation abnormalities is suggestive of a correlation between congenital lung malformations and some step of malignant transformation.

Pulmonary Carcinosarcoma Diagnosed on CryoProbe® Biopsy

Pulmonary sarcomatoid carcinomas (PSC) are an uncommon form of non-small cell lung cancer and are found in 0.4% of all lung malignancies. The five histologic variants include: Pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma.