-
Gynecologic Oncology Reports Apr 2024Sertoli-Leydig cell tumors (SLCT) are a rare form of sex cord stromal tumors. germline mutations have been identified in a portion of these cases. We report a...
Sertoli-Leydig cell tumors (SLCT) are a rare form of sex cord stromal tumors. germline mutations have been identified in a portion of these cases. We report a 15-year-old individual who presented to a well-child visit with secondary amenorrhea and subjective observations of a deepening voice and broadening shoulders. Elevations were noted in serum testosterone, inhibin B, androstenedione, and DHEA. Pelvic ultrasound and magnetic resonance imaging (MRI) revealed a left ovarian complex lesion measuring 5.8 x 5.5 x 4.6 cm. A laparoscopic unilateral salpingo-oophorectomy was performed with negative pelvic washings and a diagnosis of stage 1A, poorly differentiated/grade 3 SLCT of the ovary. Somatic and germline testing both demonstrated pathologic variations. Adjuvant chemotherapy with cisplatin/etoposide/ifosfamide (PEI) was completed under the care of pediatric oncology, and this patient is now undergoing surveillance with no signs of recurrence. Syndrome is associated with multiple tumors, including SLCT, pleuropulmonary blastoma (PPB), cystic sarcomas, and Wilms tumor among others. Patients with SLCT found to have a mutation should undergo genetic testing and cancer screening, which may help to identify neoplasms associated with the mutation at an early stage. This case will serve as a useful addition to the literature and review suggested pre-operative, operative, and surveillance guidelines.
PubMed: 38571566
DOI: 10.1016/j.gore.2024.101353 -
Journal of the Formosan Medical... Nov 2022The purpose of this study is to compare the clinical characteristics and surgical outcomes of thoracotomy and video-assisted thoracoscopic surgery (VATS) in children...
BACKGROUND
The purpose of this study is to compare the clinical characteristics and surgical outcomes of thoracotomy and video-assisted thoracoscopic surgery (VATS) in children with congenital lung malformations (CLMs) in a tertiary referring center and to report our modified biportal VATS setting.
METHODS
This is a single-center retrospective chart review study including children who underwent surgical resection for CLMs between January 2007 and December 2020. Patient characteristics and surgical outcomes were compared between open and thoracoscopy, as well as conventional VATS and biportal VATS. Biportal setting included an anterior utility wound and a camera trocar wound with one-lung ventilation.
RESULTS
A total of 100 patients were identified. Twenty patients received thoracotomy, and 80 patients received VATS (67 conventional and 13 biportal VATS). The median age at operation was 0.4 months in the thoracotomy group and 4.7 months in the VATS group. More patients in the thoracotomy group had preoperative symptoms, comorbidities, and emergent operations. The patients who underwent thoracotomy had significantly longer postoperative ICU stays, chest tube durations, hospital stays, and more complications. The pathological analysis revealed 67 congenital pulmonary airway malformations, 27 pulmonary sequestration, 6 hybrid lesions, and one accompanying pleuropulmonary blastoma. Compared to conventional VATS, the ICU stay was shorter in the biportal VATS group, with comparable operative durations, hospital stay and complications.
CONCLUSION
VATS for CLMs is associated with better postoperative recovery and fewer complications. Biportal VATS is also a safe and feasible approach.
Topics: Child; Humans; Length of Stay; Lung; Lung Diseases; Lung Neoplasms; One-Lung Ventilation; Pneumonectomy; Postoperative Complications; Retrospective Studies; Thoracic Surgery, Video-Assisted; Thoracotomy; Treatment Outcome
PubMed: 35331621
DOI: 10.1016/j.jfma.2022.03.003 -
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 -
The American Journal of Surgical... Feb 2024Germline and somatic pathogenic variants (PVs) in DICER1 , encoding a miRNA biogenesis protein, are associated with a wide variety of highly specific pathologic...
Germline and somatic pathogenic variants (PVs) in DICER1 , encoding a miRNA biogenesis protein, are associated with a wide variety of highly specific pathologic entities. The lung tumors pleuropulmonary blastoma, pulmonary blastoma (PB), and well-differentiated fetal lung adenocarcinoma (WDFLAC) are all known to harbor DICER1 biallelic variants (loss of function and/or somatic hotspot missense mutations), and all share pathologic features reminiscent of the immature lung. However, the role of DICER1 PVs in non-small cell lung cancer (NSCLC) is relatively unknown. Here, we aimed to establish the spectrum of lung pathologies associated with DICER1 hotspot PVs and to compare the mutational landscape of DICER1 -mutated NSCLC with and without hotspots. We queried DNA sequencing data from 12,146 NSCLCs featuring somatic DICER1 variants. 235 (1.9%) cases harboring ≥ 1 DICER1 PV were found and 9/235 (3.8%) were DICER1 hotspot-positive cases. Histologic review of DICER1 hotspot-positive cases showed that all but one tumor were classified as within the histologic spectrum of PB/WDFLAC, whereas all the DICER1 non-hotspot double variants were classified as lung adenocarcinomas, not otherwise specified. Comparison between the mutational landscape of DICER1 hotspot-positive and hotspot-negative cases revealed a higher frequency of CTNNB1 mutations in the hotspot-positive cases (5/9 vs. 2/225; P <0.00001). We conclude that DICER1 somatic hotspots are not implicated in the most common forms of NSCLC but rather select for morphologic features of lung tumor types such as PB and WDFLAC. As a corollary, cases showing this tumor morphology should undergo testing for DICER1 variants, and if positive, genetic counseling should be considered.
Topics: Humans; Infant, Newborn; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutation; MicroRNAs; Pulmonary Blastoma; Ribonuclease III; Germ-Line Mutation; DEAD-box RNA Helicases
PubMed: 38050371
DOI: 10.1097/PAS.0000000000002162 -
The Journal of Surgical Research Sep 2020Pleuropulmonary blastoma (PPB) is the most common primary lung cancer in children. While rare, these tumors are highly aggressive. Tumor recurrence and overall survival...
BACKGROUND
Pleuropulmonary blastoma (PPB) is the most common primary lung cancer in children. While rare, these tumors are highly aggressive. Tumor recurrence and overall survival are dependent on histologic grade and extent of surgical resection. We sought to examine our institutional experience with PPB to determine the effect of gross total resection (GTR) on recurrence and patient outcomes.
MATERIALS AND METHODS
After IRB approval, a retrospective chart review from 1998 to 2018 was performed. Cases were confirmed by histology and Dehner Grade (I to III). Data collection included demographics, treatment, extent of surgical resection, and patient outcomes.
RESULTS
Eight patients with nine procedures were identified. Histologically, three cases were type 1, 2 type 2, and four poor prognosis type 3. Three patients received neoadjuvant chemotherapy to facilitate surgical resection. The operative goal was to achieve GTR (>95%), and to this end, three partial lobectomies, five lobectomies, and one pneumonectomy were performed. All nine cases achieved GTR, of which eight had negative microscopic margins. Two patients with type III disease recurred (one locally, one distant) and died. One type 3 patient had a positive microscopic hilar margin not amenable to further resection. The patient recurred (distant) but is in remission. With respect to patient outcomes, the event-free survival was 2.3 y with an overall survival of 3.3 y.
CONCLUSIONS
From our experience, GTR of PPB is associated with minimal surgical morbidity and good overall survival. Multi-institutional studies are needed to determine if positive surgical margins affect outcomes given the morbidity of mediastinal dissection.
Topics: Chemotherapy, Adjuvant; Child, Preschool; Disease-Free Survival; Female; Humans; Infant; Infant, Newborn; Lung; Lung Neoplasms; Male; Margins of Excision; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Pneumonectomy; Prognosis; Pulmonary Blastoma; Retrospective Studies; Time Factors
PubMed: 32353636
DOI: 10.1016/j.jss.2020.03.019 -
Pediatric Blood & Cancer Mar 2022Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial...
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.
Topics: Child; DEAD-box RNA Helicases; Developing Countries; Germ-Line Mutation; Humans; Pulmonary Blastoma; Ribonuclease III; Sarcoma; Soft Tissue Neoplasms
PubMed: 34913555
DOI: 10.1002/pbc.29466 -
Familial Cancer Oct 2023Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic...
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.
Topics: Female; Humans; Germ-Line Mutation; Phenotype; Frameshift Mutation; Cysts; Ribonuclease III; Germ Cells; DEAD-box RNA Helicases
PubMed: 34331184
DOI: 10.1007/s10689-021-00271-z -
Pleuropulmonary blastoma masquerading as pneumothorax in a patient with a ventricular septal defect.Asian Cardiovascular & Thoracic Annals Oct 2022Pleuropulmonary blastoma is a rare pediatric primary lung tumor. We report a case of a child with Down syndrome and a large ventricular septal defect presenting with...
Pleuropulmonary blastoma is a rare pediatric primary lung tumor. We report a case of a child with Down syndrome and a large ventricular septal defect presenting with pleuropulmonary blastoma initially misdiagnosed as spontaneous pneumothorax. Following tube thoracostomy drainage of the pneumothorax, the child underwent surgical closure of the ventricular septal defect. However, the postoperative period was complicated by recurrent left pleural collection requiring prolonged intercostal tube drainage and two thoracotomies to evacuate the necrotic pleural material. The biopsy of the necrotic material was suggestive of type III pleuropulmonary blastoma. In view of the high propensity of metastasis associated with this variant of a tumor, the patient was started on chemotherapy. This case report highlights the possibility of pleuropulmonary blastoma presenting as pneumothorax and emphasizes the need to consider the etiology, before intervening in a child presenting with spontaneous pneumothorax.
Topics: Child; Heart Septal Defects, Ventricular; Humans; Lung Neoplasms; Pneumothorax; Pulmonary Blastoma; Treatment Outcome
PubMed: 35898165
DOI: 10.1177/02184923221113297 -
Radiology Case Reports Oct 2023Congenital pulmonary airway malformation (CPAM) is a rare congenital dysplastic malformation characterized by failure of bronchial development and localized glandular...
Congenital pulmonary airway malformation (CPAM) is a rare congenital dysplastic malformation characterized by failure of bronchial development and localized glandular overgrowth. Previously known as Congenital Cystic Adenoid Malformation (CCAM), CPAM is classified into 5 types, from type 0 to type IV, depending upon the origin of pulmonary areas of the lung, cyst size, and cyst appearance. CPAM is a rare congenital anomaly typically diagnosed prenatally in ultrasound. However, few cases are diagnosed in childhood and even fewer in adulthood. CPAM can be differentiated from pulmonary sequestration based on the origin of the arterial supply; the former has its arterial supply from the pulmonary artery, whereas pulmonary sequestration has its arterial supply from the systemic circulation. Another differential diagnosis of CPAM includes congenital bronchogenic cyst, congenital lobar emphysema, pleuropulmonary blastoma, congenital cystic bronchiectasis, and congenital diaphragmatic hernia. The most common presentation is recurrent chest infection and chest pain, whereas other presentation includes pneumothorax and hemoptysis. Here, we present a case of a 6-year-old child with recurrent episodes of fever and cough diagnosed as a type II CPAM based on computed tomography findings.
PubMed: 37539443
DOI: 10.1016/j.radcr.2023.07.018 -
Pediatric and Developmental Pathology :... 2020Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and hotspot mutations among...
Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and hotspot mutations among PPB patients. Archive records at our institution were reviewed, covering a 20-year period. Thirteen children (6 males and 7 females) with a mean age of 30.5 (range 6-83) months were included. The tumor subtypes were type I in 6 (46%), type II in 4 (31%), and type III in 3 (23%). Only tumors with type II and type III histology showed anaplasia (4/7, 57%). Median follow-up was 28 (range 9-216) months. Three-year overall survival rate was 83.3% and 3-year progression-free survival rate was 25%. Progression was seen in 60% (3/5) of type I and 66.7% (4/6) of type II and type III cases. Two patients died of disseminated disease at 9 and 44 months. Hotspot missense mutations on gene were detected in all 11 patients with available tumor tissue. We found an additional novel germline loss-of-function mutation (c.5436dupT; p.E1813*) in 1 case. To the best of our knowledge, this is the first study to investigate hotspot missense mutations on gene among the largest series of Turkish children with PPB.
Topics: Child; Child, Preschool; DEAD-box RNA Helicases; Female; Humans; Infant; Male; Mutation; Pulmonary Blastoma; Ribonuclease III
PubMed: 31603374
DOI: 10.1177/1093526619878602