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Turk Gogus Kalp Damar Cerrahisi Dergisi Jan 2024Pulmonary tumors in childhood are rare, but the majority are malignant. The histopathologic spectrum is quite diverse, including inflammatory myofibroblastic tumor,... (Review)
Review
Pulmonary tumors in childhood are rare, but the majority are malignant. The histopathologic spectrum is quite diverse, including inflammatory myofibroblastic tumor, hamartoma, primary pulmonary paraganglioma, carcinoid tumor, mucoepidermoid carcinoma, pleuropulmonary blastoma, adenocarcinoma, squamous cell carcinoma, and sarcomas. Nonspecific clinical and radiological findings result in late and incorrect diagnoses. Although surgical resection is the initial and proper treatment method, additional adjuvant therapy is dependent on both tumor stage and histopathologic type.
PubMed: 38584790
DOI: 10.5606/tgkdc.dergisi.2024.25863 -
Journal of Pediatric Surgery Case... Aug 2020Primary pulmonary malignancies are rare in childhood. The most common, pleuropulmonary blastoma (PPB), has an incidence of 25-50 cases per year in the United States...
Primary pulmonary malignancies are rare in childhood. The most common, pleuropulmonary blastoma (PPB), has an incidence of 25-50 cases per year in the United States (Knight and et al., 2019) [1]. The majority of children are diagnosed with PPB before the age of four years. PPB is divided into subtypes I, Ir (type I-regressed), II, and III, which correlates to the age of diagnosis and patient prognosis [2,3]. Here we report an unusual presentation of PPB in a teen-aged female who presented with a one month history of a non-productive cough.
PubMed: 32699772
DOI: 10.1016/j.epsc.2020.101482 -
Pediatric and Developmental Pathology :... 2021Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic variants. We investigated checkpoint inhibitor markers including...
INTRODUCTION
Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB.
MATERIAL AND METHODS
Cases were collected from departmental archives and the International PPB/ 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.
RESULTS
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 ( < .05). The density of PD1 and CD8 in the interface area was higher than within tumor ( < .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.
CONCLUSION
A small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Child; DEAD-box RNA Helicases; Humans; Lung Neoplasms; Mutation; Pulmonary Blastoma; Ribonuclease III
PubMed: 34266329
DOI: 10.1177/10935266211027417 -
The Journal of Pathology. Clinical... May 2022DICER1 syndrome is an autosomal dominant tumour predisposition syndrome usually affecting persons under 30 years of age. Many of the associated benign and malignant...
DICER1 syndrome is an autosomal dominant tumour predisposition syndrome usually affecting persons under 30 years of age. Many of the associated benign and malignant lesions occur almost exclusively in DICER1 syndrome. One such tumour, pituitary blastoma (pitB), overexpresses PRAME 500x above control levels. PRAME (PReferentially expressed Antigen in MElanoma) is expressed in malignancies that are not DICER1-related (e.g. melanoma). To address whether PRAME expression is part of the DICER1 phenotype, or simply a feature of pitB, a series of 75 DICER1-mutated specimens and 33 non-mutated specimens was surveyed using immunohistochemistry for PRAME, together with EZH2, which complexes with PRAME. In DICER1-mutated specimens, positive staining for PRAME was only seen in malignant tumours; 7 of 11 histological types and 34/62 individual tumours were positive, while non-tumourous lesions were always negative. Pleuropulmonary blastoma (PPB) showed a continuum in staining, with type I lesions being PRAME negative (n = 7) but all type II and type III lesions PRAME positive (n = 7). Similarly, cystic nephroma (CN) was negative (n = 8), with anaplastic sarcoma of the kidney being positive (n = 2). However, one atypical CN with mesenchymal cell proliferation was PRAME-positive. Embryonal rhabdomyosarcoma (RMS) with DICER1 pathogenic variants (PVs) was positive for PRAME (5/6), but the same tumour type without DICER1 PVs was also positive (9/15). Staining for EZH2 corresponded to that seen with PRAME, validating the latter. This study leads us to conclude that (1) PRAME expression occurs in two-thirds of DICER1-related malignancies; (2) PRAME may be a marker for the progression that certain DICER1-related lesions are thought to undergo, such as PPB and CN; and (3) PRAME expression in some tumours, such as RMS, appears to be an intrinsic feature of the tumour, rather than specifically related to DICER1 PVs. Therapy directed against PRAME may offer novel treatment options in patients with the DICER1 syndrome.
Topics: Antigens, Neoplasm; DEAD-box RNA Helicases; Humans; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Phenotype; Pulmonary Blastoma; Ribonuclease III; Sarcoma
PubMed: 35297207
DOI: 10.1002/cjp2.264 -
Modern Pathology : An Official Journal... Jun 2021Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic),...
Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry.
Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.
Topics: Adolescent; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Prognosis; Pulmonary Blastoma; Registries; Survival Analysis; Tumor Suppressor Protein p53; Young Adult
PubMed: 33637876
DOI: 10.1038/s41379-021-00735-8 -
EJC Paediatric Oncology Dec 2023While all childhood cancers are rare, tumors that are particularly infrequent or underrepresented within pediatrics are studied under the umbrella of the Children's...
While all childhood cancers are rare, tumors that are particularly infrequent or underrepresented within pediatrics are studied under the umbrella of the Children's Oncology Group Rare Tumor committee, divided into the Retinoblastoma and Infrequent Tumor subcommittees. The Infrequent Tumor subcommittee has traditionally included an emphasis on globally rare tumors such as adrenocortical carcinoma, nasopharyngeal carcinoma, or those tumors that are rare in young children, despite being common in adolescents and young adults, such as colorectal carcinoma, thyroid carcinoma, and melanoma. Pleuropulmonary blastoma, gonadal stromal tumors, pancreatic tumors including pancreatoblastoma, gastrointestinal stromal tumor, nonmelanoma skin cancers, neuroendocrine tumors, and desmoplastic small round cell tumors, as well as other carcinomas are also included under the heading of the Children's Oncology Group Rare Tumor committee. While substantial challenges exist in rare cancers, inclusion and global collaboration remain key priorities to ensure high quality research to advance care.
PubMed: 37829670
DOI: 10.1016/j.ejcped.2023.100024 -
Case Reports in Pathology 2014The case of 38-month-old boy is being reported who was brought to the pediatrics clinic with fever, cough, hemoptysis, and breathing difficulty. Imaging studies revealed...
The case of 38-month-old boy is being reported who was brought to the pediatrics clinic with fever, cough, hemoptysis, and breathing difficulty. Imaging studies revealed a right lower chest mass. Lobectomy and histopathological examination revealed it to be predominantly solid pleuropulmonary blastoma type II. It is a rare pediatric pleuropulmonary tumor with aggressive behavior and tendency to spread to the brain. The case is being presented to make the general histopathologist aware of this rare entity and to highlight to the pediatric physicians/surgeons, radiologists, and histopathologists the fact that lung cysts in infants and young children should be evaluated seriously and sampled thoroughly to diagnose cases of type I pleuropulmonary blastoma which will progress over time to type II or type III tumors. Also the siblings and first degree relatives of the patient should be screened for associated pulmonary and extrapulmonary benign and malignant conditions.
PubMed: 25177506
DOI: 10.1155/2014/509086 -
Children (Basel, Switzerland) Jul 2019Pleuropulmonary blastomas (PPB) are pediatric, embryonal cancers of the lung parenchyma and pleural surfaces and are among the most common DICER1-related disorders.... (Review)
Review
Pleuropulmonary blastomas (PPB) are pediatric, embryonal cancers of the lung parenchyma and pleural surfaces and are among the most common DICER1-related disorders. These tumors undergo evolution through several forms, allowing division into types I, Ir, II, and III, with correlates to the age of diagnosis and prognosis. We sought to provide a comprehensive review of the relevant literature describing the characteristics of these tumors and their multidisciplinary treatment, with an emphasis on surgical management. We describe the complementary roles of chemotherapy and surgery in the successful management of this disease. We discuss the timing of surgery and options for surgical approaches. We address the differentiation of PPB from congenital pulmonary airway malformation and the role of DICER1 testing for children with pulmonary cysts.
PubMed: 31349569
DOI: 10.3390/children6080086 -
Radiology Case Reports Oct 2021Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in children. Clinically, the malignancy is often mistaken for symptoms of respiratory tract...
Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in children. Clinically, the malignancy is often mistaken for symptoms of respiratory tract infection or pneumothorax. The neoplasm is histologically characterized by primitive blastema and a malignant mesenchymal stroma that demonstrates multidirectional differentiation. The patients with PPB are managed by multimodal therapy. We present a report of 3 cases of histopathologically diagnosed pleuropulmonary blastoma. The patients presented with chief complaints of difficulty in breathing, cough, fever and chest pain. Radiographs of the patients showed partial to complete opacification of hemithorax. Contrast enhanced computed tomography scans revealed large well defined heterogenously enhancing solid mass lesions in the hemithorax. Knowledge of types, imaging findings, staging and association with other tumors is crucial for correct diagnosis of pleuropulmonary blastoma and subsequent adequate management.
PubMed: 34401014
DOI: 10.1016/j.radcr.2021.06.046 -
Annals of Medicine and Surgery (2012) May 2023Pleuropulmonary blastoma (PPB) is a very rare, aggressive, embryonal pulmonary malignancy that mostly affects children under the age of 5 years. According to the...
Pleuropulmonary blastoma (PPB) is a very rare, aggressive, embryonal pulmonary malignancy that mostly affects children under the age of 5 years. According to the histological features, three subtypes of PPB have been recognized: type I (purely cystic), type II (grossly visible cystic and solid elements), and type III (purely solid). The authors report a case of a 10-month-old male infant with type I PPB, who was clinically misdiagnosed with pneumothorax, that he presented complaining of shortening of breath, fever, and cough. Radiographs of the patient showed right pneumothorax, so he had managed accordingly in another centre without improvement. Then Computed Tomography showed a huge right upper lobe sepated pneumocyst, which was treated surgically and the diagnosis was confirmed by combining the imaging and the histopathological examination as PPB type I. PPB is a relatively rare tumour, and it is important to put PPB with their subtypes within the differential diagnoses of any pulmonary lesion in children below the age of 5 or 6 years, as the early diagnosis will help to give early management. Hence, the patient may have a better outcome.
PubMed: 37229013
DOI: 10.1097/MS9.0000000000000514