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Virchows Archiv : An International... Aug 2020As one of the most common target organs for hematogenous spread from diverse cancers, biopsy interpretation of lung tumors is complicated by the challenging question of...
Prominent entrapment of respiratory epithelium in primary and metastatic intrapulmonary non-epithelial neoplasms: a frequent morphological pattern closely mimicking adenofibroma and other biphasic pulmonary lesions.
As one of the most common target organs for hematogenous spread from diverse cancers, biopsy interpretation of lung tumors is complicated by the challenging question of primary versus metastatic and by frequent entrapment of native respiratory glands. Nevertheless, the literature dealing with this issue is surprisingly sparse and no single study has been devoted to this topic. We reviewed 47 surgical lung specimens of non-epithelial neoplasms (38 metastases, mainly from sarcomas and 9 primary lesions) for frequency and pattern of intralesional epithelial entrapment. Respiratory epithelium entrapment was noted in 23/47 (49%) cases (diffuse in 15 and peripheral in 8). Entrapped glands frequently showed prominent regenerative and reactive changes mimicking neoplastic glands. Based on cellularity of the mesenchymal component and the extent, distribution and shape of entrapped respiratory glands, four morphological patterns were recognized: paucicellular sclerosing low-grade neoplasms containing leaflet-like glands indistinguishable from adenofibroma and fibroepithelial hamartomas (n = 11), and biphasic cellular lesions mimicking adenomyoepithelioma (n = 1), biphasic synovial sarcoma (n = 2), and pleuropulmonary blastoma (n = 1). Only a single genuine pulmonary adenofibroma was identified. This study highlights frequent respiratory epithelium entrapment in diverse non-epithelial lung tumors, both primary and metastatic. Recognition of this finding and use of adjunct IHC combined with clinical history should help to avoid misinterpretation as primary pulmonary biphasic neoplasm or as harmless adenofibroma. The vast majority of morphologically defined lung adenofibromas represent adenofibroma-like variants of histogenetically diverse entities so that a diagnosis of adenofibroma should be rendered only very restrictively and then as a diagnosis by exclusion.
Topics: Adenofibroma; Adolescent; Adult; Aged; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Respiratory Mucosa; Young Adult
PubMed: 32193604
DOI: 10.1007/s00428-020-02796-7 -
Qatar Medical Journal 2022Pleuropulmonary blastoma (PPB) is a rare malignant lung tumor in the pediatric population and occurs mainly in young children. Its clinical presentation is usually...
Pleuropulmonary blastoma (PPB) is a rare malignant lung tumor in the pediatric population and occurs mainly in young children. Its clinical presentation is usually nonspecific. We report a rare occurrence of this tumor in a 15-year-old girl, who presented with symptoms mimicking respiratory tract infection and was nonresponsive to the initial treatment. Imaging investigations revealed a large solid lesion in the left hemithorax with a mass effect on the adjacent structures. Biopsy demonstrated primitive cells with blastematous appearances, and the stroma cells were positive for vimentin and desmin, consistent with PPB. Unfortunately, she died from neutropenic sepsis while undergoing chemotherapy. This report highlights the epidemiology of PPB, its imaging and histopathological features, overview of prognosis, and clinical management.
PubMed: 35291285
DOI: 10.5339/qmj.2022.12 -
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 -
Diagnosis and treatment of pleuropulmonary blastoma in children: A single-center report of 41 cases.Journal of Pediatric Surgery Jul 2020This study was performed to investigate the age at onset, clinical manifestations, pathological types and features, treatment, and prognosis of pleuropulmonary blastoma...
OBJECTIVE
This study was performed to investigate the age at onset, clinical manifestations, pathological types and features, treatment, and prognosis of pleuropulmonary blastoma (PPB) in children in an attempt to reduce the misdiagnosis rate and achieve early detection and timely intervention.
METHODS
We retrospectively studied the clinical data of 41 pediatric patients with PPB who were treated in our center from March 2002 to November 2018. The data comprised the age at onset, clinical manifestations, characteristics of familial diseases, pathological types, surgical procedures, and prognosis.
RESULTS
Twenty male and 21 female patients were included, with a 0.95:1.00 male:female ratio. In total, 51.2% of the patients were misdiagnosed as having nonneoplastic lesions at the first presentation. The interval from symptom onset to surgery/chemotherapy ranged from 5 to 210 days. The pathological types were type I (cystic) PPB (n = 5, 11.9%), for which the median age at diagnosis was 21 months (range, 8-24 months); (solid/cystic) II PPB (n = 12, 28.6%), for which the median age at diagnosis was 37 months (range, 22-112 months); and type III (solid) PPB (n = 23, 54.8%), for which the median age at diagnosis was 39 months (range, 19-156 months). The pathologic type was undefined in one patient (2.4%). The patients were mainly treated by surgery and chemotherapy. The 5-year disease-free survival rate was 69.2%.
CONCLUSION
The clinical manifestations of PPB are nonspecific, its misdiagnosis rate is high, and it has a poor prognosis. Pediatricians should be aware of the seriousness of PPB. The possibility of PPB should be considered in children with pneumothorax, multiple pulmonary cystic lesions, a family history of pulmonary cysts, a family history of PPB, or space-occupying lesions associated with DICER1 syndromes. The lesion should be closely monitored and surgically removed if necessary. The nature of the lesion should be identified early to minimize the risk of progression of the PPB to worse types because of misdiagnosis and missed diagnosis. Multidisciplinary treatment including surgery, chemotherapy, and/or radiotherapy can be applied to patients with PPB.
TYPE OF STUDY
Treatment study.
LEVEL OF EVIDENCE
Level III.
Topics: Child; Child, Preschool; Diagnostic Errors; Female; Humans; Infant; Male; Pulmonary Blastoma; Retrospective Studies
PubMed: 31277979
DOI: 10.1016/j.jpedsurg.2019.06.009 -
Pediatric Hematology and Oncology Feb 2021Pleuropulmonary blastoma (PPB) is a rare malignant tumor in childhood cancer. This type of tumor is difficult to identify and can easily be misdiagnosed. The...
Pleuropulmonary blastoma (PPB) is a rare malignant tumor in childhood cancer. This type of tumor is difficult to identify and can easily be misdiagnosed. The International PPB protocol is a complicated and aggressive protocol. It is not easily applicable to developing countries where hospitals do not have enough resources. Here we present a challanging case of a patient successfully treated in Vietnam, using limited medical resources. The patient (22 month old, male) was diagnosed with congenital cystic adenomatoid malformation in his 1 hospital admission. After 6 months of onset, the patient was diagnosed with PPB type II in the fourth hospitalization following analysis of a lung CT scan and a pathology report. After the aggressive chemotherapy regimen, the patient had two episodes of severe neutropenia and infection from which he recovered. The patient received chemotherapy and surgery treatment at our hospital, but received radiation under general anesthesia and rehabilitation therapy to improve respiration at another hospital over 600 km away. It has been 1.5 years after entering remission, and he is starting kindergarten. Lung CT scan and pathology should be analyzed to avoid missing diagnosis of PPB in patients with cystic or mixed cystic and solid lung lesions. Biopsies from cases of suspected PPB should be sent for expert pathology review. Two factors important to the successful application of the protocol are good supportive care and the multidisciplinary collaboration between medical facilities to provide proper resources during treatment. We hope to recreate more successful outcomes not only in Vietnam but also in all developing countries.
Topics: Humans; Infant; Male; Pulmonary Blastoma; Vietnam
PubMed: 32985315
DOI: 10.1080/08880018.2020.1818905 -
Radiology Case Reports Sep 2022Pleuropulmonary blastoma (PPB) is among the rarest malignant tumors diagnosed in children. PPBs can be histopathologically classified into 3 types: cystic tumor (type...
Pleuropulmonary blastoma (PPB) is among the rarest malignant tumors diagnosed in children. PPBs can be histopathologically classified into 3 types: cystic tumor (type I), mixed cystic and solid tumor (type II), and pure solid tumor (type III). We describe a case of type III PPB that was detected in a prenatal fetus, confirmed using histopathological methods. To the best of our knowledge, this is the first case describing a type III PPB detected in a fetus. Prenatal ultrasonography is an excellent tool for detecting pulmonary lesions during the diagnostic phase, and the possibility of PPB should be considered when solid tumors are detected. Early detection can allow for the performance of full resection, leading to a better prognosis for this cancerous tumor.
PubMed: 35818452
DOI: 10.1016/j.radcr.2022.06.032 -
Pediatric Blood & Cancer Apr 2023Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood and is associated with germline DICER1 variants. Type I and Ir PPB are...
PURPOSE
Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood and is associated with germline DICER1 variants. Type I and Ir PPB are cystic lesions treated surgically, with a subset of children with type I receiving chemotherapy. Type II and III are more aggressive lesions, treated with surgery, intensive chemotherapy and potentially radiation. We sought to assess health-related quality of life (HRQoL) in children with PPB and known germline DICER1 variants.
METHODS
Children with a diagnosis of PPB or germline DICER1 pathogenic variant without history of PPB or other DICER1-related neoplasm (DICER1+ only) were enrolled in the International PPB/DICER1 Registry. Parent reports for participants aged 2-17 years for the PedsQL v.4 and PedsQL Multidimensional Fatigue Scale v.3 were collected. Fatigue, physical, and psychosocial function scores were compared.
RESULTS
Analysis included 84 participants (PPB type Ir = 20, type I = 15, type II/III = 27, DICER1+ only = 22). Total fatigue scores of participants with type I and II/III PPB were lower compared to DICER1+ only, with effect size larger in type II/III (-0.82 vs. -0.40). Total psychosocial and physical functioning scores were lower in participants with type I and type II/III PPB compared to DICER1+ only, with larger effects noted in type II/III. Female sex was suggestive of worse HRQoL for both type I/Ir and type II/III cohorts.
CONCLUSIONS
These data demonstrate the importance of regular HRQoL assessment in patients with a history of PPB as well as the importance and feasibility of studying HRQoL in children with rare tumors.
Topics: Child; Humans; Child, Preschool; Female; Adolescent; Quality of Life; Pulmonary Blastoma; Lung Neoplasms; Ribonuclease III; Registries; DEAD-box RNA Helicases
PubMed: 36424733
DOI: 10.1002/pbc.30077 -
Journal of Laparoendoscopic & Advanced... Mar 2021This study aimed to report a European multi-institutional experience about thoracoscopic management of children with congenital lung malformations. The records of 102...
This study aimed to report a European multi-institutional experience about thoracoscopic management of children with congenital lung malformations. The records of 102 patients (49 girls and 53 boys) with median age at surgery of 1 year (range 6 months-1.5 years), who underwent thoracoscopic lobectomy in five European Pediatric Surgery units, were retrospectively collected. Indications for surgery included congenital pulmonary airway malformation (CPAM) ( = 47), intra- and extralobar pulmonary sequestration ( = 34), hybrid lesion (CPAM/intralobar sequestration) ( = 2), severe bronchiectasis ( = 9), congenital lobar emphysema ( = 8), and others ( = 2). The condition was asymptomatic in 77/102 (75.5%), whereas symptoms such as recurrent pneumonia and/or respiratory distress were present in 25/102 (24.5%). Surgical procedures included 18 upper, 20 middle, and 64 lower lobe resections. No conversions to open were reported. A 3 mm sealing device and 5 mm stapler were adopted in the last 48/102 patients (47%). The median operative time was 92.2 minutes (range 74-141). The median operative time significantly decreased in patients in whom the vessel division and bronchial sealing were performed using sealing devices (75.5 minutes) compared with suture ligations (118.9 minutes) ( = .001). The median hospital stay was 3.7 days (range 2-6.2). Three/102 patients (2.9%) developed postoperative complications, including air leakage requiring pleural drainage ( = 1) (Clavien IIIb) and respiratory infection ( = 2) (Clavien II). A reoperation was required in one patient with residual pleuropulmonary blastoma (0.9%). All symptomatic patients reported resolution of symptoms postoperatively. Thoracoscopic lobectomy is a safe and effective procedure with excellent cosmetic outcome, in expert hands. Based upon our experience, we strongly recommend surgery in patients with congenital lung malformations by the first year of life, to reduce the risk of infection and make the procedure technically easier, despite the small patients' size. Surgeon's experience and use of miniaturized instruments and sealing devices remain key factors for successful outcome.
Topics: Bronchiectasis; Bronchopulmonary Sequestration; Cystic Adenomatoid Malformation of Lung, Congenital; Female; Humans; Infant; Length of Stay; Lung Diseases; Male; Operative Time; Pneumonectomy; Postoperative Complications; Pulmonary Emphysema; Retrospective Studies; Thoracoscopy; Treatment Outcome
PubMed: 33428520
DOI: 10.1089/lap.2020.0596 -
Gynecologic Oncology Mar 2020Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord...
OBJECTIVE
Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord stromal tumors, particularly Sertoli-Leydig cell tumors. The gynecologic and reproductive health of these females has not yet been described.
METHODS
All female subjects recruited from November 2011 to July 2018 participating in an epidemiologic study of families with pathogenic DICER1 germline variation were included in this cross-sectional analysis. Participant evaluation included obstetric-gynecologic history, physical examination, hormone testing, pelvic ultrasound and record review.
RESULTS
Of 64 females aged 2-72 years, fifteen underwent treatment for pleuropulmonary blastoma as children and three were treated for cervical embryonal rhabdomyosarcoma. Of nine patients reporting a history of ovarian tumors, all presented with virilization or amenorrhea; eight occurred in adolescence. Post-pubertal females with no history of ovarian tumors experienced normal pubertal development, reported regular menstrual cycles, were fertile and underwent natural menopause at median age of 52 years. Thirty-two of 33 women who tried to conceive successfully delivered liveborn children. Of these 32, 10 experienced pregnancy-related thyroid enlargement resulting in thyroidectomy within one year of pregnancy; nine others had undergone pre-pregnancy thyroidectomy.
CONCLUSION
In these DICER1-carrier females, DICER1-related gynecological tumors occurred during childhood or adolescence in some after which women generally experienced healthy reproductive lives. Individual education and screening for these tumors is warranted. The high rate of DICER1-related multinodular goiter resulting in pre- and post-pregnancy thyroidectomy underscores the importance of thyroid monitoring during pregnancy to ensure maternal and fetal wellbeing.
Topics: Adolescent; Adult; Aged; Amenorrhea; Child; DEAD-box RNA Helicases; Female; Genital Diseases, Female; Germ-Line Mutation; Humans; Male; Middle Aged; Ovarian Neoplasms; Pregnancy; Pulmonary Blastoma; Reproductive Health; Rhabdomyosarcoma, Embryonal; Ribonuclease III; Uterine Cervical Neoplasms; Young Adult
PubMed: 31952842
DOI: 10.1016/j.ygyno.2019.12.037 -
Targeting mutant dicer tumorigenesis in pleuropulmonary blastoma via inhibition of RNA polymerase I.Translational Research : the Journal of... Aug 2023DICER1 mutations predispose to increased risk for various cancers, particularly pleuropulmonary blastoma (PPB), the commonest lung malignancy of childhood. There is a...
DICER1 mutations predispose to increased risk for various cancers, particularly pleuropulmonary blastoma (PPB), the commonest lung malignancy of childhood. There is a paucity of directly actionable molecular targets as these tumors are driven by loss-of-function mutations of DICER1. Therapeutic development for PPB is further limited by a lack of biologically and physiologically-representative disease models. Given recent evidence of Dicer's role as a haploinsufficient tumor suppressor regulating RNA polymerase I (Pol I), Pol I inhibition could abrogate mutant Dicer-mediated accumulation of stalled polymerases to trigger apoptosis. Hence, we developed a novel subpleural orthotopic PPB patient-derived xenograft (PDX) model that retained both RNase IIIa and IIIb hotspot mutations and recapitulated the cardiorespiratory physiology of intra-thoracic disease, and with it evaluated the tolerability and efficacy of first-in-class Pol I inhibitor CX-5461. In PDX tumors, CX-5461 significantly reduced H3K9 di-methylation and increased nuclear p53 expression, within 24 hours' exposure. Following treatment at the maximum tolerated dosing regimen (12 doses, 30 mg/kg), tumors were smaller and less hemorrhagic than controls, with significantly decreased cellular proliferation, and increased apoptosis. As demonstrated in a novel intrathoracic tumor model of PPB, Pol I inhibition with CX-5461 could be a tolerable and clinically-feasible therapeutic strategy for mutant Dicer tumors, inducing antitumor effects by decreasing H3K9 methylation and enhancing p53-mediated apoptosis.
Topics: Humans; RNA Polymerase I; Tumor Suppressor Protein p53; Pulmonary Blastoma; Carcinogenesis; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 36921796
DOI: 10.1016/j.trsl.2023.03.001