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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 -
Tumori Apr 2020Pleuropulmonary blastoma (PPB) is a rare, aggressive mesenchymal tumor of childhood. The Italian Tumori Rari in Età Pediatrica (TREP) Registry was the first in Europe...
INTRODUCTION
Pleuropulmonary blastoma (PPB) is a rare, aggressive mesenchymal tumor of childhood. The Italian Tumori Rari in Età Pediatrica (TREP) Registry was the first in Europe dedicated to prospective data collection on rare pediatric tumors. We analyzed data from an Italian series of patients with PPB, focusing on the role of the TREP Project.
METHODS
We considered patients aged 0-14 with histologically confirmed diagnosis, registered in population-based cancer registries (before 2000) or the TREP Registry (2000 to 2014), and analyzed data on clinical characteristics, treatment, and outcome. Event-free survival (EFS) and overall survival (OS) were estimated. Relevant prognostic factors were identified performing a univariate analysis.
RESULTS
Thirty-seven cases were included (7 type I, 13 type II, 17 type III). The average diagnosis rate rose from 1.10 to 1.73 cases/year after the TREP Project started. All patients underwent surgery, 33 received chemotherapy, and 9 had radiotherapy. The median follow-up was 8.7 years. For type I, II, and III, respectively, the 5-year OS was 85.7% (33.4-97.9), 52.7% (23.4-75.5), and 57.8% (31.1-77.3); the 5-year EFS was 85.7% (33.4-97.9), 52.7% (23.4-75.5), and 52.9% (27.6-73.0). Favorable prognostic factors for EFS were Intergroup Rhabdomyosarcoma Study (IRS) stage I ( = 0.03) and T1 tumor ( = 0.05). A total of 78.3% of patients who had chemotherapy after 2000 received a standardized treatment.
CONCLUSIONS
The TREP Registry showed an excellent capacity for registering cases of PPB. Patients received homogeneous treatment after the TREP Project started. Long-term outcomes were excellent for type I and unsatisfactory for type II and III. Tumor invasiveness and IRS stage were of prognostic value.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Europe; Female; Humans; Infant; Infant, Newborn; Italy; Male; Prognosis; Pulmonary Blastoma; Rhabdomyosarcoma
PubMed: 32270754
DOI: 10.1177/0300891619871344 -
Radiology Aug 2023A 7-year-old boy with a history of pleuropulmonary blastoma after resection 6 years prior and germline mutation was being monitored by physicians at a multidisciplinary...
A 7-year-old boy with a history of pleuropulmonary blastoma after resection 6 years prior and germline mutation was being monitored by physicians at a multidisciplinary genetic predisposition clinic. He demonstrated no evidence of recurrent pleuropulmonary blastoma, and his renal US, chest radiographic, and ocular screening examination results remained normal. Per age-directed screening guidelines, he underwent thyroid US (Figs 1-3). He had no signs or symptoms of hyper- or hypothyroidism. Physical examination was notable for the absence of thyromegaly or palpable nodule. US at 12-month follow-up showed no change in size or appearance of the left lobe (not shown). However, at this time, the Thyroid Imaging Reporting and Data System (TI-RADS) classification scheme was applied to the stable left lobe finding. The findings were discussed at a multidisciplinary thyroid nodule conference, and the decision was made to bring the patient back for a short-term follow-up for limited unenhanced MRI without sedation (Fig 4). A diagnosis was made based on the follow-up imaging findings.
Topics: Male; Humans; Child; Eye; Face; Genetic Predisposition to Disease; Germ-Line Mutation; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37642568
DOI: 10.1148/radiol.222364 -
Medical and Pediatric Oncology Jan 1999
Topics: Actins; Cell Nucleus; Child, Preschool; Cytoplasm; Desmin; Endoplasmic Reticulum, Rough; Humans; Immunohistochemistry; Lung Neoplasms; Male; Mesoderm; Microscopy, Electron; Mitochondria; Muramidase; Pleural Neoplasms; Pulmonary Blastoma; Vimentin
PubMed: 9917754
DOI: 10.1002/(sici)1096-911x(199901)32:1<52::aid-mpo11>3.0.co;2-r -
Cancer Jun 1999Pleuropulmonary blastoma (PPB) is a unique dysontogenetic neoplasm of childhood. Its primitive, sarcomatous features are analogous to those of other dysembryonic or... (Review)
Review
BACKGROUND
Pleuropulmonary blastoma (PPB) is a unique dysontogenetic neoplasm of childhood. Its primitive, sarcomatous features are analogous to those of other dysembryonic or dysontogenetic tumors, such as Wilms tumor, hepatoblastoma, neuroblastoma, and embryonal rhabdomyosarcoma. PPB typically presents in young children, most younger than 5 years, as a pulmonary and/or pleural-based tumor with cystic, solid, or combined cystic and solid features. These neoplasms are characterized histologically by primitive mesenchymal or a mixture of primitive and sarcomatous components and generally have an unfavorable clinical outcome: death occurs within 1-2 years after diagnosis.
METHODS
Clinicopathologic and radiographic findings of a man age 36 years with a cystic and solid mass in the left hemithorax were reviewed and compared with previously studied cases of PPB.
RESULTS
Pathologic examination of the mass revealed a cystic and solid neoplasm composed of malignant mesenchymal cells that were immunoreactive for vimentin and muscle specific actin and focally for desmin. The architectural and cytologic appearances as well as the immunohistochemical profile were those of type II PPB.
CONCLUSIONS
To the authors' knowledge, all previously reported cases of PPB occurred in children age 12 years or younger. They believe that this case represents the first occurrence of PPB in an adult and documents the finding that, although it is uncommon, adults can develop primitive neoplasms that are usually associated with the pediatric population. In addition, the clinicopathologic features observed in the authors' adult patient were consistent with their experience with this tumor type in children. The patient died less than 1 year after diagnosis.
Topics: Adult; Humans; Immunohistochemistry; Lung Neoplasms; Male; Pleural Diseases; Pulmonary Blastoma; Radiography
PubMed: 10357407
DOI: No ID Found -
Pathology, Research and Practice Oct 2022To study the causes of the rapid progression of pleuropulmonary blastoma and to identify molecular markers related to its prognosis.
OBJECTIVES
To study the causes of the rapid progression of pleuropulmonary blastoma and to identify molecular markers related to its prognosis.
MATERIALS AND METHODS
Three pairs of fresh frozen samples of pleuropulmonary blastoma tumors and adjacent normal tissues were analyzed for proteomics, focusing on the protein molecules with significantly increased expression in tumor tissues and related to the cell cycle and DNA replication. The top five protein molecules were selected and verified by immunohistochemistry. To analyze the correlation between the expression of verified protein molecules in pleuropulmonary blastoma and early recurrence/metastasis of pleuropulmonary blastoma.
RESULTS
Compared with the adjacent normal tissues, 1759 proteins were upregulated and 967 proteins were downregulated in pleuropulmonary blastoma. The top five proteins related to the cell cycle and DNA replication were ORC2, P75, Skp2, MCM4 and PCNA. However, only P75, MCM4 and PCNA were upregulated in pleuropulmonary blastoma as determined by immunohistochemistry. Further analysis showed that the expression of P75 in the recurrence/metastasis group was significantly higher than that in the no recurrence/metastasis group, while the expression of MCM4 and PCNA was not significantly different between the recurrence/metastasis group and the no recurrence/metastasis group.
CONCLUSIONS
MCM4, PCNA and P75 may all play an important role in the progression of pleuropulmonary blastoma. Among them, P75 is related to the prognosis and may be used as a marker to predict the prognosis of pleuropulmonary blastoma.
PubMed: 36067610
DOI: 10.1016/j.prp.2022.154067 -
Turk Patoloji Dergisi 2015Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this...
Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this entity which has no systematic data associated with its incidence in order to discuss clinical, histopathological, immunohistochemical features and the differential diagnosis. A three-year-old boy presented with fever showed signs of upper respiratory tract infection. Radiological examination revealed a solid mass filling the right hemithorax. The patient underwent core needle biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined histopathologically. The tumor was composed of predominantly solid areas consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid stroma. Immunohistochemical staining of the tumor cells were positive with vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma was also infiltrated with the tumor. The patient was treated with chemotherapy and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary blastoma is a very rare childhood cancer that needs to be kept in mind in the pathological differential diagnosis of thoracic tumors in the children.
Topics: Biomarkers, Tumor; Biopsy, Needle; Chemotherapy, Adjuvant; Child, Preschool; Diagnosis, Differential; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Pneumonectomy; Predictive Value of Tests; Pulmonary Blastoma; Time Factors; Treatment Outcome
PubMed: 25560611
DOI: No ID Found -
Journal of Pediatric Hematology/oncology Jul 2012Pleuropulmonary blastoma (PPB) is a rare primary intrathoracic mesenchymal malignancy that occurs exclusively in early childhood. Twelve patients were diagnosed with PPB...
Pleuropulmonary blastoma (PPB) is a rare primary intrathoracic mesenchymal malignancy that occurs exclusively in early childhood. Twelve patients were diagnosed with PPB (1 type I, 5 type II, and 6 type III) between 1979 and 2009 at our institution. Upfront complete tumor resection was successful in 5 of 6 patients. Six patients had biopsy followed by neoadjuvant chemotherapy, 2 had complete tumor resection, and 2 had microscopic residual disease after surgery. All patients received vincristine, dactinomycin, and cyclophosphamide chemotherapy. Eight received additional chemotherapy with doxorubicin, cisplatin, etoposide, or ifosfamide. Three patients received local irradiation. The 5-year event-free and overall survivals were 33% ± 14% and 42% ± 14%, respectively. Median time to progression was 8 months. Five of 9 patients with gross total resection survived, whereas all 3 with gross residual disease died. Three of 5 survivors did not receive radiation. A high index of suspicion for PPB must be maintained in all patients diagnosed with intrathoracic sarcoma in early childhood. Gross total resection is necessary for cure, and selected patients do not require radiation therapy.
Topics: Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lung Neoplasms; Male; Pulmonary Blastoma
PubMed: 22584785
DOI: 10.1097/MPH.0b013e3182546adf -
The Annals of Thoracic Surgery Jul 2020
Topics: Diagnostic Errors; Humans; Infant; Lung Neoplasms; Pneumothorax; Pulmonary Blastoma
PubMed: 32305285
DOI: 10.1016/j.athoracsur.2020.03.033 -
Modern Pathology : An Official Journal... Oct 2020Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be...
Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and DICER1-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3-14 years). Primary sites of origin included the fallopian tube (four cases), serosal surface of the colon (one case), and pelvic sidewall (two cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB, and the remaining five had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic DICER1 variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of DICER1 pathogenic variation whose pathologic features are also recapitulated in DICER1-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor DICER1 testing.
Topics: Adolescent; Child; Child, Preschool; DEAD-box RNA Helicases; Female; Humans; Male; Mutation; Peritoneal Neoplasms; Pulmonary Blastoma; Ribonuclease III; Sarcoma
PubMed: 32415267
DOI: 10.1038/s41379-020-0558-4