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Blood Sep 2022Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a...
Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a distinct molecular signature that overlaps with nodular sclerosis classic Hodgkin lymphoma (cHL). Molecular classifiers can distinguish PMBCL from diffuse large B-cell lymphoma (DLBCL) using ribonucleic acid derived from paraffin-embedded tissue and are integral to future studies. However, given that ∼5% of DLBCL can have a molecular PMBCL phenotype in the absence of mediastinal involvement, clinical information remains critical for diagnosis. Studies during the past 10 to 20 years have elucidated the biologic hallmarks of PMBCL that are reminiscent of cHL, including the importance of the JAK-STAT and NF-κB signaling pathways, as well as an immune evasion phenotype through multiple converging genetic aberrations. The outcome of PMBCL has improved in the modern rituximab era; however, whether there is a single standard treatment for all patients and when to integrate radiotherapy remains controversial. Regardless of the frontline therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcome. With emerging data supporting the high efficacy of PD1 inhibitors in PMBCL, studies are underway that integrate them into the up-front setting.
Topics: Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Mediastinum; Rituximab
PubMed: 34496020
DOI: 10.1182/blood.2020008376 -
Advances in Anatomic Pathology Sep 2021Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection.... (Review)
Review
Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatic-type or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.
Topics: Humans; Mediastinal Neoplasms; Mediastinum; Neoplasms, Germ Cell and Embryonal
PubMed: 34029275
DOI: 10.1097/PAP.0000000000000304 -
Zentralblatt Fur Chirurgie Feb 2022If mediastinal tumours cause symptoms these are related to their anatomical localization or a paraneoplastic syndrome. The differential diagnosis is based on the...
If mediastinal tumours cause symptoms these are related to their anatomical localization or a paraneoplastic syndrome. The differential diagnosis is based on the clinical situation with finding the lesion, and, furthermore, taking into account the age and sex of the patient, and the mediastinal compartment where the lesion is located. Cross-sectional radiographic diagnostic is essential for defining the therapeutic strategy. The anterior mediastinum is dominated by thymic tumours, mediastinal lymphomas, germ cell tumours and ectopic mediastinal poiters. The middle mediastinal compartment is the most frequent place of mediastinal cystic tumours, whereas the posterior mediastinum is the domain of neurogenic tumours. For selected cases a tissue biopsy is required. Surgery is the mainstay for most mediastinal tumours. Median sternotomy is the most frequent conventional surgical technique while minimally invasive surgery with thoracoscopic and above all robot assisted operation techniques are increasingly frequent. Combined chemotherapy and modern radiotherapy are essential components of the comprehensive treatment for mediastinal tumours.
Topics: Cross-Sectional Studies; Diagnosis, Differential; Humans; Mediastinal Neoplasms; Thymoma; Thymus Neoplasms
PubMed: 35235970
DOI: 10.1055/a-1674-0693 -
Journal of Clinical Oncology : Official... Dec 2019Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need....
PURPOSE
Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade.
METHODS
In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity.
RESULTS
The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival.
CONCLUSION
Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Disease Progression; Drug Resistance, Neoplasm; Europe; Female; Humans; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Risk Assessment; Risk Factors; South America; Time Factors; United States; Young Adult
PubMed: 31609651
DOI: 10.1200/JCO.19.01389 -
Radiologie (Heidelberg, Germany) Mar 2023Mediastinal masses are common and comprise a heterogeneous spectrum of disorders. Correct diagnosis has prognostic and therapeutic consequences, which is why precise... (Review)
Review
BACKGROUND
Mediastinal masses are common and comprise a heterogeneous spectrum of disorders. Correct diagnosis has prognostic and therapeutic consequences, which is why precise localization of lesions and interdisciplinary management are essential in clinical practice. This article describes traditional divisions of mediastinum lesions and presents the new classification based on cross-sectional imaging, which was developed by the International Thymic Malignancy Interest Group (ITMIG).
OBJECTIVES
Which divisions of the mediastinum have been used so far and how does the division developed by the ITMIG differ? What are the advantages of the new mediastinal classification?
MATERIALS AND METHODS
Comparison of the previously used mediastinal classification with the new mediastinal classification developed by ITMIG and visualization of the respective methods. In addition, pathologies typical for the respective compartments are explained.
RESULTS AND CONCLUSION
The traditional compartmentalization of the mediastinum into an anterior, middle, and posterior mediastinum is not clearly defined and may lead to confusing interdisciplinary communication. Since these classifications are mostly based on projection radiographs, the proposed three-dimensional classification of the ITMIG is a development that suits the modern clinical workflow and promotes standardization. The three mediastinal compartments should thus be termed prevascular, visceral, and paravertebral.
Topics: Humans; Mediastinum; Mediastinal Neoplasms; Tomography, X-Ray Computed; Thymus Neoplasms; Diagnosis, Differential
PubMed: 36715717
DOI: 10.1007/s00117-023-01115-w -
Advances in Anatomic Pathology Sep 2021
Topics: Humans; Mediastinal Neoplasms; Mediastinum
PubMed: 34294658
DOI: 10.1097/PAP.0000000000000313 -
Histopathology Jan 2024Mediastinal tumours represent a heterogeneous group of entities derived from the manifold structures located in or adjacent to the mediastinum. Due to the occurrence of... (Review)
Review
Mediastinal tumours represent a heterogeneous group of entities derived from the manifold structures located in or adjacent to the mediastinum. Due to the occurrence of some of these tumours in characteristic mediastinal compartments, an anatomical subdivision of the mediastinum in the prevascular (anterior), visceral (middle), and paravertebral (posterior) is helpful for the differential diagnosis. Benign anterior mediastinal tumours linked to an enlargement of the thymic gland mainly consist of thymic cysts and several types of thymic hyperplasia: true thymic hyperplasia, rebound hyperplasia, lymphofollicular hyperplasia, and so-called thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features. Mature teratomas, ectopic (para)thyroid tissue, and benign thymic tumours such as thymolipoma or thymofibrolipoma represent further typical tumours of the anterior mediastinum. Pericardial, bronchogenic, or oesophageal duplication cysts predominate in the middle mediastinum, whereas neurogenic tumours and myelolipomas are characteristic findings in the posterior compartment. Vascular tumours, lipomas, adenomatoid tumours, Castleman disease, or mediastinitis are further examples of less frequent tumours or tumorous lesions affecting the mediastinum. This review focuses on benign mediastinal lesions with an emphasis on benign tumours of the thymus. Besides histology, characteristic epidemiological and clinical aspects prerequisite for the correct diagnosis and patient management are discussed.
Topics: Humans; Mediastinum; Mediastinal Neoplasms; Thymus Hyperplasia; Hyperplasia; Thymus Neoplasms
PubMed: 37988262
DOI: 10.1111/his.15088 -
Radiologic Clinics of North America Mar 2021Prevascular mediastinal masses include a wide range of benign and malignant entities. Localization of mediastinal masses to specific compartments together with... (Review)
Review
Prevascular mediastinal masses include a wide range of benign and malignant entities. Localization of mediastinal masses to specific compartments together with characteristic imaging findings and demographic and clinical information allows formulation of a focused differential diagnosis. Radiologists may use these methods to distinguish between surgical and nonsurgical cases and thus inform patient management and have an impact on outcomes. Treatment of choice varies based on the pathology, ranging from no intervention or serial imaging follow-up to surgical excision, chemotherapy, and/or radiation.
Topics: Diagnostic Imaging; Humans; Mediastinal Neoplasms; Mediastinum
PubMed: 33551078
DOI: 10.1016/j.rcl.2020.10.003 -
Annals of Diagnostic Pathology Oct 2022Spindle cell tumors originating in the mediastinum are extremely rare. Due to the profusion of structures and organs located in the mediastinum, a wide variety of... (Review)
Review
Spindle cell tumors originating in the mediastinum are extremely rare. Due to the profusion of structures and organs located in the mediastinum, a wide variety of spindle cell neoplastic processes can develop in this location. These include various different tumor types including epithelial, vascular, lipomatous, fibroblastic and neural tumors among others. Many of these different tumor types are associated with specific immunohistochemical and molecular genetic profiles that help differentiate them from each other. Although spindle cell morphology has traditionally been associated with mesenchymal neoplasms, in the mediastinum the most common spindle cell tumor is spindle cell thymoma, an epithelial rather than mesenchymal neoplasm. Except for neurogenic tumors originating in the posterior mediastinum, mesenchymal neoplasms are quite rare in mediastinal locations and require clinical correlation to rule out the possibility of a metastasis from an extra-mediastinal soft tissue or somatic sarcoma. Herein we will review the most common types of spindle cell neoplasms that occur in the mediastinum, with particular emphasis in their differential diagnosis and the role of ancillary techniques for diagnosis.
Topics: Diagnosis, Differential; Humans; Mediastinal Neoplasms; Mediastinum; Sarcoma; Thymoma; Thymus Neoplasms
PubMed: 35908333
DOI: 10.1016/j.anndiagpath.2022.152018 -
Advances in Anatomic Pathology Nov 2022Mediastinal fine needle aspirations are routinely encountered in cytopathology practice. Mediastinal lesions may pose diagnostic challenges owing to their rarity and... (Review)
Review
Mediastinal fine needle aspirations are routinely encountered in cytopathology practice. Mediastinal lesions may pose diagnostic challenges owing to their rarity and locations associated with the complexity of the mediastinal anatomic structures in the thoracic cavity. Diagnosing mediastinal lesions and guiding patient management usually require correlating with clinical and radiologic findings, being familiar with cytomorphologic features and appropriately triaging the diagnostic material for ancillary testing. This review proposes a practical approach to interpret mediastinal fine needle aspirations and emphasizes potential diagnostic pitfalls for mediastinal lesions including benign cysts, thymic neoplasms, lymphoproliferative disorders, germ cell tumors, mesenchymal tumors, and metastatic tumors.
Topics: Humans; Biopsy, Fine-Needle; Mediastinum; Thymus Neoplasms; Neoplasms, Germ Cell and Embryonal; Mediastinal Neoplasms
PubMed: 35838636
DOI: 10.1097/PAP.0000000000000355