Pleuropulmonary blastoma and hepatoblastoma are 2 well-recognized embryonal tumors of the thorax and liver respectively occurring in children. The simultaneous presentation of 2 or more pediatric embryonal tumors in the same patient is extremely rare. Specifically, cases of concomitant pleuropulmonary blastoma and hepatoblastoma in the same patient are extremely rare with only a single clinical case report published thus far. We report a case of a 25-month-old boy presenting with concomitant pleuropulmonary blastoma and hepatoblastoma, and describe the clinical, imaging, and histopathological findings. We additionally describe the underlying DICER1 alterations in both tumors. This is the first case described in Vietnam and only the second such case reported globally.

Introduction. The limited selectivity of antitumor agents is the reason behind toxicity developing as a result of chemotherapy, radiation therapy and other treatment modalities for malignant neoplasms. Hematological toxicity in patients with various types of malignant neoplasms manifests as a change in the bone marrow (BM) structure with an increase in fat in the setting of inflammatory cascade activation with the elevation of pro-inflammatory cytokines such as interleukins 2 and 6, tumor necrosis factor and others. The non-invasive quantitative BM assessment by magnetic resonance imaging (MRI) performed in the patient of interest described below allows us to move to a new level of verification of the fundamental principles of hematological toxicity. Clinical case. Here, we discuss the results of BM fat assessment in the clinical case of a 12-year-old patient who underwent rehabilitation therapy after completing treatment for pleuropulmonary blastoma of the right lung. Quantitative MRI revealed a heterogeneous fat compartment in the bones, with maximum values registered at the tumor site and in the irradiated area: in the Th4 vertebral body – 57%, in the Th5 body – 76%, Th6 – 75%, Th7 – 70%. Conclusion. The use of quantitative BM assessment in children will make it possible to develop personalized approaches to radiation therapy as well as to monitor BM reconstitution processes following the end of cancer treatment. Future research also needs to more thoroughly examine the involved pathogenetic mechanisms and the BM lipodystrophy phenomenon in cancer patients.

DICER1 syndrome is a relatively recently identified hereditary tumor predisposition syndrome, strongly associated with pleuropulmonary blastoma (PPB) and other neoplasms, but its actual status in Japan is unclear. We retrospectively performed germline DICER1 gene analysis in patients with suspected PPB at our institute between 2003 and 2022. Relevant clinical data were extracted from the medical records. Six patients with PPB were identified, of whom four harbored pathogenic germline variants in DICER1. Only one patient had a family history of childhood or juvenile cancer. Genetic testing of unaffected family members was performed in two families, revealing three asymptomatic carriers, including one infant carrier. Two of the three carriers underwent active surveillance, and no new tumors were detected on follow-up at 6 and 2.5years after diagnosis, respectively. A high prevalence of DICER1 germline variants was observed in patients with PPB, consistent with previous studies. Family history alone may be insufficient to suspect DICER1 syndrome, and thus, proactive genetic testing of family members is advisable in all cases of PPB.

Objective: To investigate the clinicopathological and molecular genetic characteristics of pediatric tumors with DICER1 mutations. Methods: A total of 90 patients diagnosed with various types of pediatric tumors at Beijing Children's Hospital, Capital Medical University, Beijing, China from July 2023 to September 2025 were included in this study. PCR amplification and Sanger sequencing were performed to detect the coding-region mutations of the DICER1 gene. The clinical, histopathological, and molecular genetic features of the cases with DICER1 mutation were then analyzed. Results: Among the 90 patients, 39 were male and 51 were female, with an age of onset ranging from 1 month to 17 years [median 7.13 (2.77, 10.37) years]. DICER1 mutations were detected in 37 patients (37/90, 41.1%). Among them, 9 cases harbored one mutation [6 pleuropulmonary blastomas (PPBs), 2 sex cord stromal tumors (SCSTs), and 1 cystic nephroma (CN)], 27 cases carried two mutations [10 PPBs, 3 anaplastic sarcomas of the kidney (ASKs), 3 SCSTs, 3 thyroid adenoma, 2 nodular thyroid goiters, 2 thyroid follicular lesions, 2 CN, 1 embryonal rhabdomyosarcoma, and 1 case with multiple primary tumors], and 1 case exhibited three mutations (bilateral ASKs). Despite variations in the site of origin, DICER1-mutant tumors shared several morphological features. Grossly, they presented as multilocular cystic, cystic-solid to solid masses. Microscopically, they exhibited a subepithelial layer of mesenchymal cells, with focal rhabdomyoblastic/chondroid/chondrosarcomatous differentiation, as well as cellular anaplasia. Germline testing using peripheral blood in the 31 patients with DICER1 mutation confirmed germline origin in 61.3% (19/31) of them. Parental analysis (n=12) demonstrated genetic inheritance in 8 cases, predominantly from families with tumor history. Germline variants scattered throughout DICER1 and consisted of loss-of-function mutations (nonsense, frameshift, and splice-site). Somatic mutations showed distinct clustering in exons 24 and 25 hotspots (codons 1705, 1709, 1809, 1810 and 1813), primarily missense variants. Notably, one multiple primary tumor case harbored a somatic mosaic p.E1705K mutation. Conclusions: DICER1 mutations are frequently detected in pediatric PPB, CN, SCST, ASK, nodular thyroid goiter, thyroid adenoma, and genitourinary rhabdomyosarcoma, which often represent as the index case of DICER1 syndrome. Performing DICER1 mutation testing in these patients not only facilitates tumor diagnosis and secondary cancer surveillance, but also enables the comprehensive genetic risk assessment and management for patient's family members.

Pathogenic germline variants in DICER1 predispose to pleuropulmonary blastoma, multinodular goitre, embryonal rhabdomyosarcomas of the uterine cervix, ovarian Sertoli-Leydig cell tumour and a broader spectrum of pathologies. Here, we report a 35-year-old female with diagnoses of pineoblastoma, embryonal rhabdomyosarcoma, leiomyosarcoma, two meningiomas, and a germline DICER1 c.4206+1G>C, p.(?) variant. The variant was classified as a variant of unknown significance (VUS) based on the current ACMG/AMP gene-specific DICER1 guidelines. Additional functional analysis showed that the variant clearly abrogates the function of DICER1 and therefore PS3_Supporting evidence is included in the classification. Based on this the variant is reclassified as likely pathogenic. Moreover, our data suggest that the current ACMG/AMP gene-specific DICER1 guidelines should be modified in relation to the level of evidence strength (moderate to strong/very strong) for exon 22 skipping as well as to the use of the functional evidence (PS3) code.

Abstract Introduction/Objective Pulmonary blastoma (PB) is a rare, highly aggressive biphasic tumor of sarcomatoid carcinoma subtype. These neoplasms frequently harbor CTNNB1 mutations leading to aberrant nuclear expression of the beta-catenin protein. Additionally, some adult cases harbor DICER1 mutations. Herein, we describe a unique case of PB diagnosed in pregnancy. Methods/Case Report A 30-year-old female at 35-weeks gestation presented with complaints of shortness of breath and chest pain. Imaging revealed a 7.9 cm mediastinal mass involving the pericardium and left upper lobe. A biopsy and subsequent resection showed a biphasic neoplasm composed of fetal adenocarcinoma with a lesser component of undifferentiated carcinoma and focal high-grade carcinoma with neuroendocrine differentiation. The mesenchymal component consisted of a primitive blastema-like stroma with foci of immature cartilage. The glandular component was positive for CAM5.2, TTF-1, and SALL-4. Both the glandular and mesenchymal components had aberrant cytoplasmic and nuclear staining of beta-catenin. Synaptophysin was focally positive in the fetal adenocarcinoma and poorly differentiated adenocarcinoma. Stains for desmin, glypican 3, PLAP, AFP, CDX2, CD30, GATA3, MyoD1, myogenin, Napsin, OCT3/4, PAX-8, and SOX10 were negative. NGS studies detected mutations in CTNBB1 and DICER1 genes. Results NA Conclusion Pulmonary blastoma is a rare, aggressive biphasic neoplasm with distinctive morphologic, immunophenotypic, and molecular features. Awareness of this entity is critical to accurately render this challenging diagnosis.

Abstract A one‐and‐a‐half‐year‐old dog was presented to our institution, with a 48‐hour history of coughing and lethargy, for investigation of a suspected spontaneous pneumothorax. Computed tomography revealed a pneumothorax and the presence of two cavitary lesions affecting the right cranial and right caudal pulmonary lobes. Following stabilisation, lung lobectomy of the affected lobes was performed via median sternotomy, and the patient recovered with no complications. Histopathological analysis of the submitted tissues identified pleuropulmonary blastoma. Repeat computed tomography 4 months post‐operatively revealed no evidence of lesion recurrence or pneumothorax. To the authors’ knowledge, this is the first report describing the computed tomography appearance and surgical management of pleuropulmonary blastoma in a dog.

Congenital chest lesions are a diverse group of anomalies which can have similar imaging appearances, thus creating diagnostic challenges. Increased availability and technical advances of ultrasound and magnetic resonance imaging provide improved characterization of these lesions. Improved characterization permits earlier recognition and enhanced prognostication. As such, radiologists are essential in guiding patient management for congenital chest lesions. We present the following imaging review to simplify the diagnostic dilemma of the most common fetal chest lesions, including congenital diaphragmatic hernia, the congenital lung malformation spectrum, and pleuropulmonary blastoma.

Clinical characteristics and treatment analysis of pulmonary blastoma (PB): a report of 17 cases.

A 17-month-old male presented with a 4-week history of cough, and a CT scan revealed a large right intrathoracic mass with metastases to the brain and femur. Tumor biopsy demonstrated a high-grade malignant neoplasm with histological and immunostaining features most suggestive of, but not entirely typical for type III pleuropulmonary blastoma (PPB). Molecular analysis identified a YAP1::MAML2 gene fusion and a complex copy number profile, with no mutations in DICER1 or TP53. The patient initially improved with chemotherapy, but progressive brain metastases led to palliative care, and he passed away 10 months later. This is the first reported case of a YAP1::MAML2 fusion in a pleuropulmonary neoplasm.

Introduction: This study quantified the concordance of pre- and postnatal imaging and pathology diagnoses of fetal lung lesions. Methods: This is a retrospective review of patients seen at a single fetal center from 2014 to 2024. Results: A total of 138 patients with prenatally diagnosed lung lesions were identified. Patients with an associated congenital diaphragmatic hernia (n = 7) and patients with neither postnatal imaging nor surgical pathology (n = 11) were excluded. Overall, 86.7% had postnatal imaging; of these, 79.8% had postnatal CT findings consistent with prenatal imaging. Overall, 68.3% had surgical resection at our institution. The remaining patients had surgery elsewhere or did not pursue resection of the lesion. Of those 82 patients, 90.2% had a pathologic diagnosis concordant with their prenatal MRI and 97.1% had a pathologic diagnosis concordant with postnatal CT. The most common case of discordance between pre- and postnatal imaging was bronchial atresia (71.4%, 15/21), which was originally called a CPAM/BPS/hybrid lesion on prenatal imaging. The most striking case of discordance between imaging and pathology was a pleuropulmonary blastoma initially called a CPAM on prenatal MRI. Conclusion: Congenital lung lesions may evolve during pregnancy, highlighting the value of postnatal imaging to further characterize the lesions and assess the appropriateness of patients for surgical resection.

ABSTRACTPleuropulmonary blastoma (PPB) is a rare, highly aggressive pulmonary tumor that typically presents in the pediatric population. The overall prognosis of PPB is poor, although type I PPB can regress spontaneously. In this case report, the authors present a 3.5‐year‐old boy histopathologically diagnosed with PPB type III, who underwent three courses of the ifosfamide, vincristine, actinomycin D, and doxorubicin (IVADO) chemotherapy regimen after surgical resection. Although the initial post‐chemotherapy evaluations showed no residual or metastatic tumor, based on PET‐CT scan findings, it relapsed 4 months after the last chemotherapy course. Finally, the patient expired due to disease progression. In addition to the case presentation, the authors provide an overview of PPB and discuss how this case illustrates key diagnostic and management challenges in advanced PPB type III.

Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients.

Pleuropulmonary blastoma (PPB) is a rare pediatric sarcoma often associated with DICER1 mutations. However, additional genetic factors may influence disease progression and prognosis. This study identifies a novel mutation in the GPC3 gene and evaluates its potential as a prognostic biomarker in PPB. Whole-genome sequencing (WGS) was conducted on blood samples from a three-generation family with PPB. Candidate genes were prioritized based on autosomal recessive inheritance patterns and association with PPB. Immunohistochemistry was used to assess GPC3 expression in PPB tumor tissues, adjacent areas, and congenital pulmonary airway malformation (CPAM) samples. Kaplan-Meier survival analysis was performed, comparing survival outcomes in patients with varying levels of GPC3 expression. Seventeen candidate genes, including GPC3, were identified. A novel missense mutation in the GPC3 gene was confirmed, with significantly higher GPC3 expression observed in PPB tissues than in CPAM or adjacent non-tumor tissues. Survival analysis revealed that patients with high GPC3 expression (GPC3+++) exhibited a markedly lower two-year survival rate (30%) compared to moderate (GPC3++, 75%) and low (GPC3+, 90.9%) expression groups (p = 0.0035). The correlation between elevated GPC3 levels and poor prognosis suggests GPC3 as a potential biomarker for disease severity in PPB. Our findings propose GPC3 as a novel mutation contributing to PPB susceptibility and progression. Elevated GPC3 expression correlates with poorer survival outcomes, indicating its potential as a prognostic marker and therapeutic target in PPB management.

High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a therapeutic option that allows potentiating the antitumor effect in patients with malignant neoplasms (MNs) belonging to the high-risk group. However, despite the effectiveness of this method, the risks of developing infectious and toxic complications in the early and late post-transplantation period are higher than the risks associated with treatment according to standard protocols and can significantly worsen the results of transplantation. We carried out a retrospective analysis of the results of auto-HSCT in a cohort of 156 patients with high-risk solid MNs treated at the L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation in 2020–2023. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology. The study included 78 (50%) boys and 78 (50%) girls, the median age of the patients was 8 years 7 months (9 months – 17 years 8 months). Auto-HSCT was performed in 90 (57.7%) patients with neuroblastoma, 25 (16.0%) – with Ewing's sarcoma, 16 (10.3%) – with germ cell tumors, 13 (8.4%) – with nephroblastoma, 7 (4.5%) – with retinoblastoma, 3 (1.9%) – with medulloblastoma, 1 (0.6%) patient with pleuropulmonary blastoma and 1 (0.6%) patient with sialoblastoma. We used the following conditioning regimens: treosulfan + melphalan (n = 116), carboplatin + thiotepa + etoposide (n = 17), melphalan (n = 13), carboplatin + thiotepa + etoposide + cyclophosphamide (n = 10). Depending on the clinical indications and the treatment protocol used, 136 (87.2%) patients underwent one course of HDCT, and 20 (12.8%) patients underwent tandem HDCT. In most patients, the median recovery time for granulocytes and platelets was 11 (8–19) days and 14 (12–21) days, respectively. The most common infectious complications in patients after auto-HSCT were mucositis (89.1%), neutropenic enterocolitis (76.9%), febrile neutropenia (71.2%), less often: catheter-associated bloodstream infection (9%), pneumonia (14.1%), acute respiratory distress syndrome (0.6%). As regards toxic complications, all patients had emetic syndrome, 98 (62.8%) had dermatological toxicity, 9 (5.8%) had hemorrhagic cystitis, 116 (74.3%) had hepatic toxicity, 14 (9%) had neurotoxicity, 102 (65.4%) had moderate nutritional insufficiency. Episodes of hemorrhagic syndrome due to thrombocytopenia were observed in 44.2% of patients. After auto-HSCT, most patients develop chemotherapy-induced (including infectious) complications, which can not only significantly disrupt the patients’ well-being and quality of life, but also, depending on the severity, pose a threat to their life. The correct choice of conditioning regimen, effective collection of hematopoietic stem cells, complex accompanying therapy, timely diagnosis and treatment of complications can significantly improve the results of auto-HSCT in children with high-risk solid MNs.

Pulmonary mesenchymal cystic hamartoma (MCH) is an exceptionally rare benign tumor characterized by cystic-solid architecture and biphasic epithelial-mesenchymal components. We report a 56-year-old woman with a 2.6-cm right lower lobe mass, histologically composed of pseudostratified ciliated epithelium, glandular components, and primitive mesenchymal cells with cartilaginous/adipose differentiation. Tumor cells showed diffuse moderate cytoplasmic BCL-2/CD56 staining, weak-moderate nuclear PR positivity, and a low Ki-67 index (< 2%). RNA sequencing identified a novel EWSR1::CREM fusion, involving exon 13 of EWSR1 and intron 5/exon 6 of CREM. This finding expands the molecular spectrum of FET::CREB-driven tumors and distinguishes MCH from mimics such as glomus tumor and pleuropulmonary blastoma. The patient remained recurrence-free at 4-year follow-up, underscoring the benign nature of this lesion. This study highlights three critical insights: (1) Molecular significance: The EWSR1::CREMfusion suggests shared oncogenic mechanisms with intracranial mesenchymal tumors and primary pulmonary myxoid sarcoma. (2) Diagnostic refinement: Integration of molecular profiling resolves diagnostic ambiguity in cystic lung lesions. (3) Clinical relevance: Routine molecular testing should be considered for ambiguous cystic lung lesions to refine classification. Conservative management is appropriate for molecularly confirmed MCH. Our findings emphasize the necessity of integrating histomorphology, immunohistochemistry, and molecular profiling in diagnosing rare pulmonary entities. Further studies are needed to elucidate the role of EWSR1::CREM in MCH pathogenesis and explore targeted therapeutic strategies.

Pulmonary blastoma (PB) is a rare and aggressive lung malignancy. Prior studies were confounded by inconsistent histological classifications, particularly before the 2021 World Health Organization (WHO) reclassification. This study aimed to characterize PB’s epidemiological features and prognostic factors under the updated 2021 WHO criteria. Data on patients diagnosed with PB from the The Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020 were collected. Kaplan-Meier curves were used to evaluate overall survival (OS), and univariate/multivariate Cox regression analysis was employed to identify independent factors affecting prognosis. PB affected females more frequently (61.5%) and occurred across all ages without a clear peak. The median tumor size was 77.83 mm, with upper/lower lung lobes being common sites. Surgical resection was performed in 73.8% of patients. The 1-, 3-, and 5-year OS rates were 70.3%, 57.2%, and 51.9%, respectively. Multivariate analysis revealed age, histological grade, and surgical status as independent prognostic factors. This study provides the first comprehensive analysis of PB under the 2021 WHO classification, demonstrating improved survival outcomes compared to historical reports. Age, histological grade, and surgical intervention are critical prognostic determinants. These findings underscore the importance of accurate histological classification and surgical resection in optimizing PB management.

This report aimed to underscore the significance of pulmonary blastoma, a rare entity with limited literature, by contributing insights into its clinical features, diagnostic approaches, and treatment modalities. Additionally, it emphasizes the critical role of a multidisciplinary approach in the effective management of this complex and challenging disease.

Type I Cystic Pleuropulmonary Blastoma in a 12-Month Infant.

A 5-year-old boy with right-sided chest pain and fever was diagnosed with pleuropulmonary blastoma, confirmed by thoracoscopic biopsy. Initial imaging showed a large hypermetabolic mass in the right lower lobe. After 2 cycles of chemotherapy, FDG PET/CT demonstrated significant solid component shrinkage and increased cystic airspaces with decreased hypermetabolic activity. After surgery, pathology confirmed type II pleuropulmonary blastoma. Nine months later, recurrent disease was detected on follow-up FDG PET/CT. Patient underwent further tumor resection, followed by radiation and chemotherapy. This case illustrates the evolving FDG PET/CT findings, and recurrence of pleuropulmonary blastoma after treatment.