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Pediatric Blood & Cancer Jun 2021Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the...
Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).
Topics: Adolescent; Child; Child, Preschool; DEAD-box RNA Helicases; Humans; Lung Neoplasms; Neoadjuvant Therapy; Pulmonary Blastoma; Registries; Ribonuclease III
PubMed: 33826235
DOI: 10.1002/pbc.29045 -
Children (Basel, Switzerland) Jul 2019Pleuropulmonary blastomas (PPB) are pediatric, embryonal cancers of the lung parenchyma and pleural surfaces and are among the most common DICER1-related disorders.... (Review)
Review
Pleuropulmonary blastomas (PPB) are pediatric, embryonal cancers of the lung parenchyma and pleural surfaces and are among the most common DICER1-related disorders. These tumors undergo evolution through several forms, allowing division into types I, Ir, II, and III, with correlates to the age of diagnosis and prognosis. We sought to provide a comprehensive review of the relevant literature describing the characteristics of these tumors and their multidisciplinary treatment, with an emphasis on surgical management. We describe the complementary roles of chemotherapy and surgery in the successful management of this disease. We discuss the timing of surgery and options for surgical approaches. We address the differentiation of PPB from congenital pulmonary airway malformation and the role of DICER1 testing for children with pulmonary cysts.
PubMed: 31349569
DOI: 10.3390/children6080086 -
Modern Pathology : An Official Journal... Jun 2021Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic),...
Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry.
Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.
Topics: Adolescent; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Prognosis; Pulmonary Blastoma; Registries; Survival Analysis; Tumor Suppressor Protein p53; Young Adult
PubMed: 33637876
DOI: 10.1038/s41379-021-00735-8 -
Zhongguo Fei Ai Za Zhi = Chinese... Sep 2018Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion, migration, drug sensitivity and... (Review)
Review
Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion, migration, drug sensitivity and prognosis. Discoveries and development upon on tumor-driver genes and targeted therapy paved the way on dealing with cancer diagnosis and treatment. However, the existence of tumor heterogeneity makes malignant tumor more hardly to overcome. It is generally present and far more complicated during the process of cancer recurrence, development and evolution. Thus, it has becoming key areas in precision medicine regarding to designing optimal therapeutic approaches targeting the mechanisms and phenotypes of tumor heterogeneity, based on novel detecting techniques and new concepts and theory. This review summarized the current references on tumor heterogeneity, in order to better understand the function and mechanisms, and eventually manage tumor heterogeneity through various methods. .
Topics: Evolution, Molecular; Humans; Mutation; Neoplasms
PubMed: 30201072
DOI: 10.3779/j.issn.1009-3419.2018.09.11 -
The Journal of Pathology. Clinical... May 2022DICER1 syndrome is an autosomal dominant tumour predisposition syndrome usually affecting persons under 30 years of age. Many of the associated benign and malignant...
DICER1 syndrome is an autosomal dominant tumour predisposition syndrome usually affecting persons under 30 years of age. Many of the associated benign and malignant lesions occur almost exclusively in DICER1 syndrome. One such tumour, pituitary blastoma (pitB), overexpresses PRAME 500x above control levels. PRAME (PReferentially expressed Antigen in MElanoma) is expressed in malignancies that are not DICER1-related (e.g. melanoma). To address whether PRAME expression is part of the DICER1 phenotype, or simply a feature of pitB, a series of 75 DICER1-mutated specimens and 33 non-mutated specimens was surveyed using immunohistochemistry for PRAME, together with EZH2, which complexes with PRAME. In DICER1-mutated specimens, positive staining for PRAME was only seen in malignant tumours; 7 of 11 histological types and 34/62 individual tumours were positive, while non-tumourous lesions were always negative. Pleuropulmonary blastoma (PPB) showed a continuum in staining, with type I lesions being PRAME negative (n = 7) but all type II and type III lesions PRAME positive (n = 7). Similarly, cystic nephroma (CN) was negative (n = 8), with anaplastic sarcoma of the kidney being positive (n = 2). However, one atypical CN with mesenchymal cell proliferation was PRAME-positive. Embryonal rhabdomyosarcoma (RMS) with DICER1 pathogenic variants (PVs) was positive for PRAME (5/6), but the same tumour type without DICER1 PVs was also positive (9/15). Staining for EZH2 corresponded to that seen with PRAME, validating the latter. This study leads us to conclude that (1) PRAME expression occurs in two-thirds of DICER1-related malignancies; (2) PRAME may be a marker for the progression that certain DICER1-related lesions are thought to undergo, such as PPB and CN; and (3) PRAME expression in some tumours, such as RMS, appears to be an intrinsic feature of the tumour, rather than specifically related to DICER1 PVs. Therapy directed against PRAME may offer novel treatment options in patients with the DICER1 syndrome.
Topics: Antigens, Neoplasm; DEAD-box RNA Helicases; Humans; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Phenotype; Pulmonary Blastoma; Ribonuclease III; Sarcoma
PubMed: 35297207
DOI: 10.1002/cjp2.264 -
Nature Reviews. Cancer Oct 2021A systematic approach to understanding the noncoding genome in cancer promises to improve cancer diagnosis and therapy. Tracking the landscape of gene control in...
A systematic approach to understanding the noncoding genome in cancer promises to improve cancer diagnosis and therapy. Tracking the landscape of gene control in individual patients and single cells yields many insights for inherited and somatic mutations in cancer, extrachromosomal oncogene amplifications, and cancer immunotherapy. New technologies and bold therapeutic approaches are paving the way to truly envisage personalized cancer medicine in the future.
Topics: Humans; Immunotherapy; Mutation; Neoplasms; Precision Medicine
PubMed: 34172966
DOI: 10.1038/s41568-021-00381-x -
Hormones & Cancer Dec 2015
Topics: Cell Transformation, Neoplastic; Female; Hormones; Humans; Journal Impact Factor; Male; Neoplasms
PubMed: 26305704
DOI: 10.1007/s12672-015-0234-1 -
Seminars in Cancer Biology Feb 2020The macro-metastasis/organ parenchyma interface (MMPI) was previously considered an inert anatomical border which sharply separates the affected organ parenchyma from... (Review)
Review
The macro-metastasis/organ parenchyma interface (MMPI) was previously considered an inert anatomical border which sharply separates the affected organ parenchyma from the macro-metastatic tissue. Recently, infiltrative growth of macro-metastases from various primary tumors was described in the brain, liver and lung, with significant impact on survival. Strikingly, the MMPI patterns differed between entities, so that at least nine different patterns were described. The MMPI patterns could be further classified into three major groups: displacing, epithelial and diffuse infiltrating. Additionally, macro-metastases are a source of further tumor cell dissemination in the affected organ; and these intra-organ metastatic dissemination tracks starting from the MMPI also vary depending on the anatomical structures of the colonized organ and influence disease outcome. In spite of their relevance, MMPIs and organ-specific dissemination tracks are still largely overlooked by many clinicians, pathologists and/or researchers. In this review, we aim to address this important issue and enhance our current understanding of the different MMPI patterns and dissemination tracks in the brain, liver and lung.
Topics: Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Neoplasms; Organ Specificity
PubMed: 31647982
DOI: 10.1016/j.semcancer.2019.10.012 -
Blood Advances Jan 2021Pathogenic germline variants in DICER1 underlie an autosomal dominant, pleiotropic tumor-predisposition disorder. Murine models with the loss of DICER1 in hematopoietic... (Review)
Review
Pathogenic germline variants in DICER1 underlie an autosomal dominant, pleiotropic tumor-predisposition disorder. Murine models with the loss of DICER1 in hematopoietic stem cell progenitors demonstrate hematologic aberrations that include reductions in red and white blood cell counts, hemoglobin volume, and impaired maturation resulting in dysplasia. We investigated whether hematologic abnormalities such as those observed in DICER1-deficient mice were observed in humans with a pathogenic germline variant in DICER1. A natural history study of individuals with germline pathogenic DICER1 variants and family controls conducted through the National Cancer Institute (NCI) evaluated enrollees at the National Institutes of Health Clinical Center during a comprehensive clinical outpatient visit that included collecting routine clinical laboratory studies. These were compared against normative laboratory values and compared between the DICER1 carriers and controls. There were no statistical differences in routine clinical hematology laboratory studies observed in DICER1 carriers and family controls. A review of the medical history of DICER1 carriers showed that none of the individuals in the NCI cohort developed myelodysplastic syndrome or leukemia. Query of the International Pleuropulmonary Blastoma/DICER1 Registry revealed 1 DICER1 carrier who developed a secondary leukemia after treatment of pleuropulmonary blastoma. We found limited evidence that the hematologic abnormalities observed in murine DICER1 models developed in our cohort of DICER1 carriers. In addition, no cases of myelodysplastic syndrome were observed in either the NCI cohort or the International Pleuropulmonary Blastoma/DICER1 Registry; 1 case of presumed secondary leukemia was reported. Abnormalities in hematologic indices should not be solely attributed to DICER1. This trial was registered at www.clinicaltrials.gov as #NCT01247597.
Topics: Animals; DEAD-box RNA Helicases; Germ Cells; Germ-Line Mutation; Hematology; Mice; Neoplasms; Pulmonary Blastoma; Ribonuclease III
PubMed: 33570641
DOI: 10.1182/bloodadvances.2020002651 -
Canadian Medical Association Journal Jan 1970A case of rapidly growing solitary tumour of the right upper lobe of the lung in a 72-year-old man is presented. It shows the typical histological appearance of a...
A case of rapidly growing solitary tumour of the right upper lobe of the lung in a 72-year-old man is presented. It shows the typical histological appearance of a pulmonary blastoma. Only 13 cases were published previously, none from Canada. It is a matter of opinion whether pulmonary blastoma should be classified as a separate entity or as a distinct form of carcinosarcoma.
Topics: Aged; Autopsy; Humans; Lung Neoplasms; Male
PubMed: 5411455
DOI: No ID Found