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DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma.Modern Pathology : An Official Journal... Jan 2022DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common... (Review)
Review
DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation.
Topics: Causality; Germ-Line Mutation; Humans; Lung Neoplasms; Pleural Neoplasms; Pulmonary Blastoma; Ribonuclease III; Syndrome
PubMed: 34599283
DOI: 10.1038/s41379-021-00905-8 -
Orphanet Journal of Rare Diseases Dec 2008Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the... (Review)
Review
Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.
Topics: Humans; Mesothelioma; Pleural Neoplasms; Tomography, X-Ray Computed
PubMed: 19099560
DOI: 10.1186/1750-1172-3-34 -
European Respiratory Review : An... Mar 2021Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and...
Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and increase in scientific understanding in these areas in the past decade. With regard to pleural infection, the rising incidence remains worrying. An increased awareness allowing earlier diagnosis, earlier escalation of therapy and the use of validated risk stratification measures may improve outcomes. In pleural malignancy, research has enabled clinicians to streamline patient pathways with focus on reducing time to diagnosis, definitive management of malignant pleural effusion and achieving these with the minimum number of pleural interventions. Trials comparing treatment modalities of malignant pleural effusion continue to highlight the importance of patient choice in clinical decision-making. This article aims to summarise some of the most recent literature informing current practice in these two areas.
Topics: Humans; Pleural Diseases; Pleural Effusion, Malignant; Pleural Neoplasms; Thoracic Surgical Procedures
PubMed: 33650525
DOI: 10.1183/16000617.0002-2020 -
European Respiratory Review : An... Mar 2021Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread... (Review)
Review
Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread prohibition of asbestos production and supply, its incidence continues to increase. It is heterogeneous in its presentation and behaviour, and diagnosis can be notoriously difficult. Identification of actionable gene mutations has proven challenging and current treatment options are largely ineffective, with a median survival of 10-12 months.However, the past few years have witnessed major advances in our understanding of the biology and pathogenesis of mesothelioma. This has also revealed the limitations of existing diagnostic algorithms and identified new treatment targets.Recent clinical trials have re-examined the role of surgery, provided new options for the management of associated pleural effusions and heralded the addition of targeted therapies. The increasing complexity of mesothelioma management, along with a desperate need for further research, means that a multidisciplinary team framework is essential for the delivery of contemporary mesothelioma care.This review provides a synthesised overview of the current state of knowledge and an update on the latest research in the field.
Topics: Asbestos; Biology; Humans; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms
PubMed: 33472960
DOI: 10.1183/16000617.0226-2020 -
Respiratory Medicine Oct 2015A tumorlike condition of the pleura is any nonmalignant lesion of the pleura or within the pleural space that could be confused with a pleural tumor on initial imaging.... (Review)
Review
A tumorlike condition of the pleura is any nonmalignant lesion of the pleura or within the pleural space that could be confused with a pleural tumor on initial imaging. Tumorlike conditions of the pleura are relatively rare compared with neoplastic lesions such as mesotheliomas and metastases. Imaging-based diagnosis of these conditions can be difficult due to the similarity of appearance. Thus, recognition of certain imaging patterns and interpretation of these patterns in the clinical context are important. Pleural endometriosis, thoracic splenosis, thoracolithiasis, foreign bodies, pleural pseudotumors and pleural plaques are significant examples of focal tumorlike conditions discussed in this article. Computed tomography is the mainstay imaging technique for the primary assessment of pleural disease, but other imaging methods, such as magnetic resonance imaging and positron-emission tomography, can be of great support in the diagnosis.
Topics: Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Mesothelioma; Middle Aged; Neoplasm Metastasis; Pleural Diseases; Pleural Neoplasms; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 26094051
DOI: 10.1016/j.rmed.2015.06.004 -
Annals of Oncology : Official Journal... Aug 2018Malignant pleural mesothelioma (MPM) is a rare malignancy with some unique characteristics. Tumor biology is aggressive and prognosis is poor. Despite more knowledge on... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare malignancy with some unique characteristics. Tumor biology is aggressive and prognosis is poor. Despite more knowledge on histology, tumor biology and staging, there is still a relevant discrepancy between clinical and pathologic staging resulting in difficult prediction of prognosis and treatment outcome, making treatment allocation more challenging than in most other malignancies. After years of nihilism in the late 80s, a period of activism started evaluating different treatment protocols combined with research driven mainly by academic centers; at the time, selection was based on histology and stage only. This period was important to gain knowledge about the disease. However, the interpretation of data was difficult since selection criteria and definitions varied substantially. Not surprisingly, until now there is no common agreement on best treatment even among specialists. Hence, a review of our current concepts is indicated and personalized treatment should become applicable in the future. Surgery was and still is an issue of debate. In principle, surgery is an effective approach as it allows macroscopic complete elimination of a tumor, which is relatively resistant to medical treatment. It helps to set the clock back and other therapies that have also just a limited effect can be applied sequentially before or after surgery. Furthermore, to date best long-term outcome is reported from surgical series in combination with other modalities. However, part of the community considers surgery associated with too high morbidity and mortality when balanced to the limited life expectancy. This criticism is understandable, since poor results after surgery are reported. The present article will review the indication for surgery and discuss the different procedures available for macroscopic complete resection-such as lung-preserving (extended) pleurectomy/decortication as well as extrapleural pneumonectomy to illustrate that 'The surgeon is still there!'
Topics: Chemotherapy, Adjuvant; Clinical Trials as Topic; Disease-Free Survival; Humans; Lung; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Pleura; Pleural Neoplasms; Pneumonectomy; Prognosis; Radiotherapy, Adjuvant; Treatment Outcome
PubMed: 29905765
DOI: 10.1093/annonc/mdy195 -
Acta Bio-medica : Atenei Parmensis Aug 2017Malignant pleural mesothelioma is the most frequent primary neoplasm of the pleura and its incidence is still increasing.This tumor has a strong association with... (Review)
Review
Malignant pleural mesothelioma is the most frequent primary neoplasm of the pleura and its incidence is still increasing.This tumor has a strong association with exposure to occupational or environmental asbestos, often after a long latent period of 30-40 years.Plain chest radiography (CXR) is usually the first-line radiologic examination, but the radiographic findings are nonspecific due to its limited contrast resolution and they need to be complemented by other imaging modalities such as computed tomography (CT), magnetic resonance Imaging (MRI), Positron emission tomography-computed tomography (PET-CT) and ultrasound (US).The aim of this paper is to describe the imaging features of this malignancy, underlining the peculiarity of CXR, CT, MRI, PET-CT and US and also focusing on diagnostic workup, based on the literature evidence and according to our experience.
Topics: Humans; Lung Neoplasms; Magnetic Resonance Imaging; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Positron Emission Tomography Computed Tomography; Radiography, Thoracic; Tomography, X-Ray Computed; Ultrasonography
PubMed: 28845826
DOI: 10.23750/abm.v88i2.5558 -
Archives of Pathology & Laboratory... Aug 2018- Pleural pathology has been dominated by discussions relating to the diagnosis, prognosis, etiology, and management of malignant mesothelioma. However, there exists a... (Review)
Review
CONTEXT
- Pleural pathology has been dominated by discussions relating to the diagnosis, prognosis, etiology, and management of malignant mesothelioma. However, there exists a diverse group of other neoplasms that involve the pleura; the most common by far is metastatic carcinoma, usually of pulmonary origin. Other metastatic tumors of varied histogenesis do occur but are less common. Primary pleural neoplasms other than diffuse malignant mesothelioma are either uncommon or rare and have received less attention.
OBJECTIVE
- To provide a review of those diverse tumors that can involve the pleura other than mesothelioma in order to facilitate their accurate diagnosis.
DATA SOURCES
- Review of relevant literature published via PubMed and other search engines.
CONCLUSIONS
- A wide variety of tumors can involve the pleura. In most cases, the approach of considering the morphologic features with appropriate immunohistochemistry, in the correct clinical context, allows for a confident diagnosis. For a number of those soft tissue tumors that are well recognized in the pleura, such as solitary fibrous tumor, desmoid-type fibromatosis, synovial sarcoma, and epithelioid hemangioendothelioma, novel markers now exist based on an understanding of the individual tumors' molecular characteristics. Primary pleural lymphomas are rare with poor prognosis. They represent localized specific diffuse large B-cell lymphomas, with either post-germinal center B-cell or plasma cell lineage, arising in the context of either immunodeficiency or immune sequestration and with viral infection.
Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Mesothelioma; Pleural Neoplasms
PubMed: 30040453
DOI: 10.5858/arpa.2017-0537-RA -
International Journal of Molecular... May 2023Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is typically diagnosed in a locally advanced stage, making it not eligible for radical surgery and requiring... (Review)
Review
Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is typically diagnosed in a locally advanced stage, making it not eligible for radical surgery and requiring systemic treatment. Chemotherapy with platinum compounds and pemetrexed has been the only approved standard of care for approximately 20 years, without any relevant therapeutic advance until the introduction of immune checkpoint inhibitors. Nevertheless, the prognosis remains poor, with an average survival of only 18 months. Thanks to a better understanding of the molecular mechanisms underlying tumor biology, targeted therapy has become an essential therapeutic option in several solid malignancies. Unfortunately, most of the clinical trials evaluating potentially targeted drugs for MPM have failed. This review aims to present the main findings of the most promising targeted therapies in MPM, and to explore possible reasons leading to treatments failures. The ultimate goal is to determine whether there is still a place for continued preclinical/clinical research in this area.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Pleural Neoplasms; Pemetrexed; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37298116
DOI: 10.3390/ijms24119165 -
Targeted Oncology Jul 2022Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a... (Review)
Review
Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asbestos; Bevacizumab; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Pleural Neoplasms
PubMed: 35906513
DOI: 10.1007/s11523-022-00900-2