Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). It is also considered a distinct type of non-Hodgkin lymphoma (NHL) in the World Health Organization (WHO) classification system. It occurs in the thymus gland. The small gland in the center of the chest behind the sternum where lymphocytes mature, multiply and become _{T cells}. or lymph nodes in the center of the chest. On microscopic histopathological analysis, large-sized cells and alveolar fibrosis are characteristic findings of primary mediastinal large B-cell lymphoma. The incidence of primary mediastinal large B-cell lymphoma increases with age; the median age at diagnosis is 35 years. The symptoms of the primary mediastinal large B-cell lymphoma include fever, weight loss, night sweats, skin rash, facial swelling, cough, shortness of breath, and painless swelling in the neck, axilla, groin, thorax, or abdomen. Lymph node or mediastinal mass biopsy is diagnostic of primary mediastinal large B-cell lymphoma. The predominant therapy for primary mediastinal large B-cell lymphoma is chemotherapy. Adjunctive radiotherapy, stem cell transplant, and biological therapy may be required. The optimal therapy for primary mediastinal large B-cell lymphoma depends on the clinical presentation.

There is no established system for the classification of primary mediastinal large B-cell lymphoma. However it was designated as a separate disorder in 2001 by World health organization. There are different stages of primary mediastinal large B-cell lymphoma, depending on the metastatic stage of disease.

Primary mediastinal large B-cell lymphoma arises from thymus. The small gland in the center of the chest behind the sternum where lymphocytes mature, multiply and become T cells. or lymph nodes in the center of the chest. On microscopic histopathological analysis, large-sized cells and alveolar fibrosis are characteristic findings of primary mediastinal large B-cell lymphoma. The incidence of primary mediastinal large B-cell lymphoma increases with age. The pathophysiology primarily involves constitutional activation of JAK2 pathway through different genetic mechanisms involved.

The cause of primary mediastinal large B-cell lymphoma has not been identified.

Primary mediastinal large B-cell lymphoma must be differentiated from other diseases that cause swollen face, superior vena cava syndrome, and fever, night sweats and weight loss such as hodgkin’s lymphoma, thymoma, and other non hodgkin’s lymphomas.

Primary mediastinal large B-cell lymphoma represents 4% of overall non-hodgkins lymphomas and affects females predominantly.

There are no established risk factors for Primary mediastinal large B-cell lymphoma.

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for primary mediastinal large B-cell lymphoma.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

In 1864 and 1865, Virchow and Cohnheim independently described non-Hodgkin lymphoma and called it lymphosarcoma and psedoleukemia respectively. Since then, tremendous efforts of many scientifics have been continuing to provide more precise and comprehensive with pathology, staging, and treatment of Hodgkin’s lymphoma.

• In 1864, Virchow , a German physician , described lymph node enlargement not related to leukemia as lymphosarcoma a subdivision of aleukimic type of leukemias.
• In 1865, Cohnheim, a German-Jewish physician , used the term pseudolukemia to describe all common lymphadenopathy and splenomegaly.
• In 1871, Bilroth, a Prussian-born Austrian surgeon, was the first to described a case of non-Hodgkin lymphoma, and coined the term malignant lymphoma.^[1]
• In 1958, Denis Parsons Burkitt, an Irish surgeon, first discovered Burkitt’s lymphoma while working in Africa.^[2]
• In 1925, follicular lymphoma was described by Brill and Symmers independently.^[3]
• In 1956, Henry Rappaport and his colleagues proposed the Rappaport classification, based on cellular morphology, this became the first widely accepted classification of non-Hodgkin lymphomas.
• In 1966, Armed Forces Institute of Pathology (AFIP) modified the the Rappaport classification in the”Tumors of the Hematopoietic System”.^[4]
• In 1982, National Cancer Institute introduced the working formulation, an amalgamation translating all previous classifications, which defined three grades of non-Hodgkin lymphoma.^[5]
• In 1992, Banks first coined the term mantle cell lymphoma (MCL).^[6]
• In 1994, the Revised European-American Classification of Lymphoid Neoplasms (REAL) classified non-Hodgkin’s lymphoma, based on immunologic, genetic and clinical characteristics of the disorders in addition to histopathologic characteristics of the tumor cells.^[7]
• Since 2008 the World Health Organisation (WHO) has been starting a project with committees of international hematopathologists and oncologists, who have developed lists and definitions of disease entities to ensure that the classification will be helpful to clinicians. They proposed their first approach in 2008 and after that, the relevant Clinical Advisory Committee (CAC) updates its latest revision every few years. ^[8][9]

• In 1997, FDA approved rituximab, to treat patients with B-cell non-Hodgkin lymphoma that did not responds to other treatments.^[10]

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Template:Primary mediastinal large B-cell lymphoma classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

There is no established system for the classification of primary mediastinal large B-cell lymphoma. However it was designated as a separate disorder in 2001 by World health organization. There are different stages of primary mediastinal large B-cell lymphoma, depending on the metastatic stage of disease.

Primary mediastinal B-cell lymphoma was recognized as a sub type of diffuse large B-cell lymphoma since the 1994 in Revised European American Lymphoma Classification.^[1]

• It has been regarded as a unique clinical and biological entity since the 2001 according to World Health Organization classification.^[2]

• Staging for primary mediastinal large B-cell lymphoma is provided in the following table:^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2], Sowminya Arikapudi, M.B,B.S. [3]

Primary mediastinal large B-cell lymphoma arises from thymus. The small gland in the center of the chest behind the sternum where lymphocytes mature, multiply and become _{T cells}. or lymph nodes in the center of the chest. On microscopic histopathological analysis, large-sized cells and alveolar fibrosis are characteristic findings of primary mediastinal large B-cell lymphoma. The incidence of primary mediastinal large B-cell lymphoma increases with age. The pathophysiology primarily involves constitutional activation of JAK2 pathway through different genetic mechanisms involved, which are described.

• Primary mediastinal large B-cell lymphoma arises within the thymus.^[1][2]
• Patients present with a localized anterosuperior mediastinal mass.
• The mass is often bulky and frequently invades adjacent structures such as lungs, pleura, or pericardium.
• Spreads to supraclavicular and cervical lymph nodes.
• Pathophysiologically, tumor grows through constitutive STAT6 phosphorylation and DNA-binding activity.^[3]
• STAT6 phosphorylation activates Interleukin 4/ interleukin-13 signalling pathway.
• Constitutive STAT6 phosphorylation and DNA-binding activity is detected is proved through immunohistochemical analysis.
• Another proposed mechanism of autocrine pathway is amplification of JAK 2 pathway which causes phosphorylation of IL-4 and IL-13 subsequently.
• The Janus kinase 2 is also constitutively phosphorylated in the primary mediastinal large B-cell lymphoma.
• Primary mediastinal large B-cell lymphoma is treated with JAK2 inhibitor AG490, resulted in partially decreased STAT6 phosphorylation, which suggests that JAK2 is partially involved in STAT6 activation in these cells.

• Genes involved in the pathogenesis of primary mediastinal large B-cell lymphoma include:
  • Comparative genomic hybridzation demonstrated gains in chromosome 9p24 and 2p15
  • Genomic hybridization in chromosome X-p11.4-21
  • Translocations involving the CIITA gene^[4]
  • Amplification of the REL oncogene^[5]
  • Hyperdiploid karyotypes, often with gains in the region on chromosome 9p containing the JAK2 gene and the genes encoding PD-L1 and PD-L2, ligands for the receptor PD-1^[6]
  • The B cell leukemia/lymphoma 2 (BCL-2) gene and B cell leukemia 6 (BCL-6) gene rearrangements can occur.^[7]
  • Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11A(XL) protein.^[8]
  • Immunoglobulin genes clonally rearranged.

• The immunophenotype of primary mediastinal large B-cell lymphoma is determined by histochemistry or flow cytometry.
• The tumor cells express B cell-associated antigens:^[7]
  • CD19
  • CD20
  • CD22
  • CD79a
  • CD45
• Weak expression of CD30 is often present.
• The tumor cells also stain for TRAF-1 and nuclear c-Rel
• These two markers are also expressed by the Reed-Sternberg cells, but are not present in other forms of diffuse large B cell lymphoma. ^[9]
• Other markers that are relatively specific for primary mediastinal large B-cell lymphoma are CD200 and MAL.^[10][11]

• On microscopic histopathological analysis, large-sized cells and alveolar fibrosis are characteristic findings of primary mediastinal large B-cell lymphoma.
• The tumor is composed of large cells with variable nuclear features, cells may resemble:^[12][13]
  • Centroblasts
  • Large centrocytes
  • Multilobated cells, often with pale or “clear” cytoplasm
  • Less frequently, the tumor cells resemble immunoblasts
  • Reed-Sternberg-like cells
  • Some cases have also presented with fine, compartmentalizing sclerosis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

The cause of primary mediastinal large B-cell lymphoma has not been identified.

The cause of primary mediastinal large B-cell lymphoma has not been identified.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

Primary mediastinal large B-cell lymphoma must be differentiated from other diseases that cause swollen face, superior vena cava syndrome, and fever, night sweats and weight loss such as hodgkin’s lymphoma, thymoma, and other non hodgkin’s lymphomas.

• Primary mediastinal large B-cell lymphoma must be differentiated from other diseases that cause swollen face, superior vena cava syndrome, and fever, night sweats and weight loss such as hodgkin’s lymphoma, thymoma, and other non hodgkin’s lymphomas.

• The differentiation is determined on the basis of biopsy findings and immunophenotype, which are as follows:

• Thymoma
  • Thymic epithelial cells stain for epithelial markers such as keratin and epithelial membrane antigen.^[1]
• Hodgkin’s lymphoma^[2]
  • Reed-Sternberg cells typically express CD15 and CD30
• Thymic carcinoma
  • The lymphocytes have phenotype of mature T cells (CD1a-, CD3+, and CD4+ or CD8+.^[3]
• Acute myeloid Leukemia
  • Myeloblasts immature cells with large nuclei, prominent nucleoli, and a variable amount of pale blue cytoplasm with auer rods^[4]
• Diffuse large B-cell lymphoma
  • Involvement of bone marrow or distant lymph nodes is indicative of systemic DLBCL with secondary mediastinal involvement.
• Mediastinal germ cell tumor^[5]
  • Germ cell tumor markers such as beta-human chorionic gonadotropin [hCG] and alpha fetoprotein are positive.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

Primary mediastinal large B-cell lymphoma represents 4% of overall non-hodgkins lymphomas and affects females predominantly.

• Primary mediastinal large B-cell lymphoma comprises of 7% of overall diffuse large B cell lymphoma‘s and 2.4 % of all Non hodgkin lymphomas. ^[1]

• The incidence of primary mediastinal large B-cell lymphoma increases with age; the median age at diagnosis is 35 years.^[2]

• Females are more commonly affected with primary mediastinal large B-cell lymphoma than males.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

There are no established risk factors for Primary mediastinal large B-cell lymphoma.

There are no established risk factors for primary mediastinal large B-cell lymphoma.

Template:Primary mediastinal diffuse large B-cell lymphoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

There is insufficient evidence to recommend routine screening for primary mediastinal larger B-cell lymphoma.

There is insufficient evidence to recommend routine screening for primary mediastinal larger B-cell lymphoma.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

Primary mediastinal large B-cell lymphoma is usually a fast-growing lymphoma. Patients often have localized disease in the chest at first. If left untreated, primary mediastinal large B-cell lymphoma can causeshortness of breath, cough, chest pain. Primary mediastinal large B-cell lymphoma can also partially block superior vena cava that carries blood from the upper body to the heart and causes superior vena cava syndrome.

• Primary mediastinal large B-cell lymphoma is usually a fast-growing lymphoma.
• Patients often have localized disease in the chest at first.
• If left untreated, primary mediastinal large B-cell lymphoma can cause:
  • shortness of breath
  • cough
  • chest pain
• Primary mediastinal large B-cell lymphoma can also partially block the main vein (superior vena cava) that carries blood from the upper body to the heart and cause superior vena cava syndrome.

Common complications of [disease name] include:

• Compression of vessels in the neck often causes following symptoms :
  • Dyspnea
  • Swollen face
  • Fullness of head on bending forwards
  • Arm swelling
  • Dysphagia
  • Cerebral edema
  • Headache
  • Confusion
  • Coma
• Potential Oncologic emergencies are:
  • Acute airway obstruction
  • Pericardial tamponade
  • Thrombosis of major neck or superior thoracic veins
• Patients with large mediastinal masses are at increased risk of respiratory or cardiac arrest during general anesthesia or heavy sedation.
• Patients who present with cardiorespiratory symptoms or radiographic evidence of tracheal obstruction are at greatest risk of perioperative respiratory morbidity.

• Less common complication includes:
  • Tumor lysis syndrome is caused by massive tumor cell lysis and the release of large amounts of potassium, phosphate, and uric acid into the systemic circulation.
  • Deposition of uric acid and/or calcium phosphate crystals in the renal tubules results in acute renal failure.

• The bone marrow is rarely affected by this type of lymphoma.
• Recurrence or relapse often occurs in organs or tissues outside the lymph nodes (extranodal sites), such as the kidneys or central nervous system.

• Prognosis is generally good after aggressive therapy, which usually combines chemotherapy with mediastinal irradiation. However if relapse occurs , it depends on paucity of molecular level of tumor cells, and their ability to evade immune system.
• Initial studies suggest that a more favorable course may be predicted by one of the following :
  • Low tumor metabolic activity which is determined by decreased total lesion glycolysis (a measure of FDG uptake) on FDG-PET imaging at baseline or after initial therapy. ^[1]
  • Further study is needed to confirm the prognostic value of PET before it can be used to modify initial treatment plans.