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Clinical Radiology Apr 2021Hereditary ovarian tumour syndromes are a diverse group of hereditary syndromes characterised by the development of specific histotypes of ovarian neoplasms. While BRCA... (Review)
Review
Hereditary ovarian tumour syndromes are a diverse group of hereditary syndromes characterised by the development of specific histotypes of ovarian neoplasms. While BRCA syndromes are exclusively associated with high-grade serous carcinomas, patients with Lynch syndrome show a preponderance of endometrioid subtype of ovarian and endometrial carcinomas. Distinct non-epithelial phenotypes, such as sex cord stromal tumours with annular tubules, Sertoli-Leydig cell tumours, and small cell carcinoma of the hypercalcaemic type occur in patients with Peutz-Jeghers, DICER1, and rhabdoid tumour predisposition syndromes, respectively. Gorlin-Goltz syndrome is characterised by the development of bilateral, multiple ovarian fibromas in 14-24% of patients. Ovarian steroid cell tumours and broad ligament papillary cystadenomas are characteristically found in women with von Hippel-Lindau syndrome. Recent studies have allowed the characterisation of tumour genetics and associated oncological pathways that contribute to tumourigenesis. Implications of the diagnosis of these syndromes on screening, management, and prognosis are discussed.
Topics: Basal Cell Nevus Syndrome; Brain Neoplasms; Carcinoma, Ovarian Epithelial; Colorectal Neoplasms, Hereditary Nonpolyposis; DEAD-box RNA Helicases; Female; Genes, BRCA1; Genes, BRCA2; Germ-Line Mutation; Humans; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Ovarian Neoplasms; Peutz-Jeghers Syndrome; Pulmonary Blastoma; Rhabdoid Tumor; Ribonuclease III; von Hippel-Lindau Disease
PubMed: 33353730
DOI: 10.1016/j.crad.2020.11.116 -
Pediatric Blood & Cancer Dec 2021Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome.
BACKGROUND
Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
Topics: Adolescent; Child; Child, Preschool; Combined Modality Therapy; Humans; Infant; Neoplasm Recurrence, Local; Pulmonary Blastoma; Retrospective Studies
PubMed: 34486213
DOI: 10.1002/pbc.29268 -
Acta Chirurgica Belgica Jun 2024Pleuropulmonary blastoma (PPB) is a very rare tumor of the chest seen predominantly in young children with great heterogeneity and clinical, biochemical, and biological...
Pleuropulmonary blastoma (PPB) is a very rare tumor of the chest seen predominantly in young children with great heterogeneity and clinical, biochemical, and biological complexity and recognized, described, and classified as distinct from the pulmonary blastoma typically encountered in adults. Unfortunately, it has a poor and dismal prognosis and is mainly classified as cystic (type 1), mixed type (type 2), and solid (type 3). Herein, we present one case of PPB type 2 presenting clinically with a right pulmonary abscess, a rare clinical presentation of PPB, which was initially treated with surgery, and after approximately 1 year of follow-up, pulmonary rest-recurrence and central nervous system secondary deposits were detected. When a large pleural-based mass is identified in a young child, PPB should also be considered, especially in a patient with a positive oncological family history. Suggestive findings include the absence of chest wall invasion, presence of pleural fluid, right-sided location, and heterogeneous native (NECT) low attenuation with variable postcontrast enhancement. The authors believe that a modern therapeutic approach should consider these results for a better understanding of the genetic nature and complex mechanism and process of PPB disease development (both clinical and preclinical data concerning PPB pathophysiology are still lacking and are not completely understood) so that it would be possible to establish new possible therapeutic options (i.e. nuclear medicine theranostics in PPB treatment, developments and innovation in FLASH radiotherapy and proton therapy) and approaches, and so that, given the severity of the disease, it would be possible to indicate the importance of genetic testing and counseling of close relatives. In line with the previous, the rapid development of artificial intelligence could potentially bring the development of a novel fusion of radio mics and semantic features and MRI-based machine learning in distinguishing PPB from similar pathology.
PubMed: 38842285
DOI: 10.1080/00015458.2024.2365503 -
The American Journal of the Medical... Dec 2023
Topics: Humans; Pulmonary Blastoma
PubMed: 37652203
DOI: 10.1016/j.amjms.2023.08.009 -
Diagnostic Cytopathology Feb 2024Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from... (Review)
Review
INTRODUCTION
Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from congenital cystic lung lesions is crucial due to significant prognostic and therapeutic differences. Cytologic features have rarely been described. Establishing a cytodiagnosis is challenging owing to its rarity, lack of awareness, and multiple morphologic mimics.
MATERIALS AND METHODS
This was a retrospective study conducted over 8 years. The histopathology and cytopathology databases were searched for all pediatric PPB cases. The corresponding cytologic samples were reviewed to identify characteristic features that can help distinguish PPB from its mimics.
RESULTS
There was a total of six cases of pediatric PPB reported during the study period. Of these, four (66.7%) presented as intrathoracic, and two (33.3%) as pleural-based masses. Cytology smears showed discretely scattered and perivascular arrangements of round-oval tumor cells with background eosinophilic stromal material. The tumor cells were mildly pleomorphic (n = 3) with round nuclei, fine chromatin, inconspicuous nucleoli, and scanty cytoplasm; however, three cases showed marked anaplasia, and one each showed necrosis and rhabdoid differentiation. On immunocytochemistry (4/6), these were positive for vimentin and desmin and negative for WT1, chromogranin, SALL4, cytokeratin, CD45, and CD99. FISH (1/6) did not show N-Myc amplification.
CONCLUSIONS
Knowledge of the characteristic cytomorphological and immunocytochemical features of PPB is vital to establish a prompt and accurate cytodiagnosis with appropriate clinicoradiologic correlation.
Topics: Humans; Child; Child, Preschool; Lung Neoplasms; Retrospective Studies; Pleural Neoplasms; Pulmonary Blastoma
PubMed: 37964698
DOI: 10.1002/dc.25254 -
Medical Archives (Sarajevo, Bosnia and... Feb 2021Pleuropulmonary blastoma (PPB) is a rare, but aggressive tumor in the pediatric population. PPB is a dysontogenetic neoplasm of childhood that involves the lungs and/or...
INTRODUCTION
Pleuropulmonary blastoma (PPB) is a rare, but aggressive tumor in the pediatric population. PPB is a dysontogenetic neoplasm of childhood that involves the lungs and/or pleura. Young relatives of children with PPB have an increased incidence of neoplasias and dysplasias. According to tumor tissue histopathology, PPB evolves from a cystic to solid state over time. PPBs can be sub-classified as type I (purely cystic), type II (having both cystic and solid elements), and type III (completely solid). Type II and type III tumors may be associated with metastasis, with the brain being the most common metastatic site. Due to the primitive nature of cells in the tumor mass, PPBs are very aggressive tumors that are resistant to therapy. The prognosis depends on the histopathology content and tumor type. Respiratory problems are the main complaint and diagnosis can be made only after additional examinations. Genetic relations through family members are associated with mutations in the DICER1 gene; between 60-80% of patients with PPBs are positive for DICER1 mutations. Mosaicism has also been reported.
AIM
The aim was to present a case of a 4 month-old infant with type II PPB, who had a negative result for DICER1 mutation in next generation sequencing. To detail the clinical presentation of this patient, we present radiographic and ultrasound findings and results of histopathological analysis, as well as genetic and scintigraphic findings and chemotherapy treatment.
CASE REPORT
Here we describe the genetic analysis of a patient with PPB who was negative for mutations in DICER1 and who had no relatives with disease. This patient underwent radical resection of the tumor and began therapy, but subsequently died after developing leukopenia and sepsis.
CONCLUSION
This case provides an example of a patient with PPB who was negative for DICER1 mutation upon genetic analysis and emphasizes the potential for disease that does not involve mutation of this gene.
Topics: Fatal Outcome; High-Throughput Nucleotide Sequencing; Humans; Infant; Lung Neoplasms; Mutation; Prognosis; Pulmonary Blastoma; Ribonuclease III
PubMed: 34012202
DOI: 10.5455/medarh.2021.75.61-65 -
Translational Pediatrics Apr 2024-associated tumors are heterogeneous and affect several organs. -associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27...
BACKGROUND
-associated tumors are heterogeneous and affect several organs. -associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27 (H3K27me3) loss in nucleus by immunohistochemistry.
METHODS
We explored the H3K27me3 immunostaining pattern in other -associated tumors. Twelve tumors from eleven patients with confirmed mutations (sporadic and germline) data from a pancancer next-generation sequencing panel, and four tumors of pleuropulmonary blastoma (PPB) were retrieved from our database and stained with anti-H3K27me3 antibody.
RESULTS
The H3K27me3 expression in the nucleus showed heterogeneous mosaic loss in neoplastic Sertoli cell components in three of the five cases of moderately to poorly differentiated Sertoli-Leydig cell tumors. Among two tumors of -associated primary intracranial sarcoma, one showed complete loss of H3K27me3 in all neoplastic cells, whereas the other showed mosaic loss in the sarcomatous spindle cells. One -associated tumor with epithelial and mesenchymal differentiation, including pulmonary blastoma and PPB, showed mosaic loss of glandular epithelial and mesenchymal components. Four cases of type II PPB and a single case of type III PPB showed a similar mosaic loss of H3K27me3 staining restricted to large spindle cell components. All other components in all tumors-including Leydig cells; the areas of epithelial, cartilaginous, and rhabdomyomatous differentiation; and all cells of the remaining three cases (one papillary thyroid carcinoma and two cases of PPB type I)-demonstrated retained H3K27me3 staining.
CONCLUSIONS
H3K27me3 expression is not universally lost in -associated tumors and thus is not predictive of mutation status. The mosaic regional loss of H3K27me3 immunostaining is consistent in PPB type II and III, which can be a helpful diagnostic marker for these tumors and suggests a similarity to -associated intracranial sarcoma.
PubMed: 38715664
DOI: 10.21037/tp-24-61 -
International Journal of Clinical and... 2019Pulmonary blastoma (PB) is a very rare malignant lung tumor, consisting of immature epithelium and/or mesenchymal tissue. The two tissue components are derived from the...
Pulmonary blastoma (PB) is a very rare malignant lung tumor, consisting of immature epithelium and/or mesenchymal tissue. The two tissue components are derived from the same precursor cells. In this study, we present a case of a 29-year-old woman with classical biphasic pulmonary blastoma, who underwent right middle lobe resection and subsequent treatment. Due to the low incidence rate and the reclassification of PB, no standard treatment is available currently. In our case, the patient received radiotherapy and chemotherapy and is doing well at 6 months' follow up. In retrospect, we review the pathology, clinical manifestations, imaging features and treatment of this disease.
PubMed: 31933843
DOI: No ID Found -
Radiology Case Reports Jul 2021We are presenting a rare case with the simultaneous occurrence of pleuropulmonary blastoma and an intra lobar pulmonary sequestration. Although there have been cases...
We are presenting a rare case with the simultaneous occurrence of pleuropulmonary blastoma and an intra lobar pulmonary sequestration. Although there have been cases reported previously with pleuropulmonary blastoma associated with congenital pulmonary malformations, the association with an intra lobar pulmonary sequestration is very rare. The patient, a female, 6-month-old child arrived at our pediatric service with the clinic of cough, respiratory distress, and fever after being treated for 2 weeks for left lung bronchopneumonia according clinical signs and radiographic description but without clinical improvements. Contrast enhanced CT images showed the simultaneous presence of 2 different lesions in the left lung, a heterogeneous mass in the superior lobe without delineation with mediastinal structure compatible with a pleuropulmonary blastoma and a consolidation in the inferior lobe with bronchogram present and a systemic vessel feeding compatible with an intra lobar pulmonary sequestration, both confirmed by histologic examinations after the surgical intervention. Although it is very rare, the simultaneous presence of these distinct embryogenic lesions may occur and radiologist should be aware as the imaging diagnosis may be very helpful for the further management of the patient.
PubMed: 34007392
DOI: 10.1016/j.radcr.2021.04.040 -
Annals of Diagnostic Pathology Oct 2022DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary... (Comparative Study)
Comparative Study
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.
DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary blastomas (PPBs) and 6 sarcomas by mutation analysis, whole transcriptome sequencing and methylation profiling. 9/10 patients were female. PPB patients were 0-4 years. 3/4 were alive; 2 without disease. One patient died of metastatic disease (median follow-up, 16 months). Sarcoma patients were 16-56 years. Locations included: uterine cervix/corpus (3/1), soft tissue back/shoulder (1) and paravertebral (1). 5/6 patients were alive; 2 developed metastases: intracranial (1) and lung and kidney (1) (median follow-up, 17 months). The deceased patient previously had a PPB and a Sertoli-Leydig cell tumor. Histologically, tumors showed atypical primitive-looking cells with incomplete rhabdomyoblastic differentiation and cartilage (n = 5). Immunohistochemistry demonstrated desmin- (n = 9/10), myogenin- (n = 6/10) and keratin positivity (n = 1/1). Eight cases harbored biallelic DICER1 mutations with confirmed germline mutations in 4 cases. Two cases showed a monoallelic mutation. By RNA expression- and methylation profiling, distinct clustering of our cases was seen demonstrating a close relationship on (epi)genetic level and similarities to embryonal rhabdomyosarcoma. In conclusion, this study shows overlapping morphological, immunohistochemical and (epi)genetic features of PPBs and DICER1-associated high-grade sarcomas, arguing that these neoplasms form a spectrum with a broad clinicopathological range.
Topics: Female; Humans; Male; DEAD-box RNA Helicases; Desmin; Keratins; Mutation; Myogenin; Pulmonary Blastoma; Rhabdomyosarcoma, Embryonal; Ribonuclease III; RNA; Soft Tissue Neoplasms
PubMed: 35779311
DOI: 10.1016/j.anndiagpath.2022.152002