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| {{SI}} | | {{Primary mediastinal large B-cell lymphoma}} |
| | '''For patient information, click [Primary mediastinal large B-cell lymphoma(patient information)|here]]''' |
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| '''For patient information, click [[Insert page name here (patient information)|Insert page name here]]'''
| | {{CMG}}; {{AE}} {{Badria}} {{AS}} |
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| {{CMG}}; {{AE}}{{Badria}} {{AS}} | | {{SK}} |
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| {{SK}}: Mediastinal B-cell lymphoma; Mediastinal large B-cell lymphoma, PMBCL, Primary mediastinal B-cell lymphoma.
| | ==[[Primary mediastinal large B-cell lymphoma overview|Overview]]== |
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| == Overview == | | ==[[Primary mediastinal large B-cell lymphoma historical perspective|Historical Perspective]]== |
| 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 <sub>[[T cell|T cells]]</sub>. or [[Lymph node|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. | |
| ==Classification==
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| * 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.<ref name="pmid8068936">{{cite journal |vauthors=Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC |title=A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group |journal=Blood |volume=84 |issue=5 |pages=1361–92 |date=September 1994 |pmid=8068936 |doi= |url=}}</ref>
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| * It has been regarded as a unique clinical and biological entity since the 2001 according to World Health Organization classification.<ref name="pmid27399089">{{cite journal |vauthors=Liu PP, Wang KF, Xia Y, Bi XW, Sun P, Wang Y, Li ZM, Jiang WQ |title=Racial patterns of patients with primary mediastinal large B-cell lymphoma: SEER analysis |journal=Medicine (Baltimore) |volume=95 |issue=27 |pages=e4054 |date=July 2016 |pmid=27399089 |pmc=5058818 |doi=10.1097/MD.0000000000004054 |url=}}</ref>
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| ==Pathophysiology== | | ==[[Primary mediastinal large B-cell lymphoma classification|Classification]]== |
| * Primary mediastinal large B-cell lymphoma most likely arises within the [[thymus]].<ref name="seer.cancer.gov">Primary mediastinal large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5318/. Accessed on March 7, 2016 </ref><ref name="pmid2423430">{{cite journal |vauthors=Addis BJ, Isaacson PG |title=Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin |journal=Histopathology |volume=10 |issue=4 |pages=379–90 |date=April 1986 |pmid=2423430 |doi= |url=}}</ref>
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| * Patients present with a [[Localized disease|localized]] anterosuperior [[mediastinal mass]].
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| * The mass is often bulky and frequently invades adjacent structures such as [[lungs]], [[pleura]], or [[pericardium]].
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| * Spreads to [[supraclavicular]] and [[cervical]] [[lymph nodes]].
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| * Pathophysiologically, tumor grows through constitutive [[STAT]] 6 [[phosphorylation]] and DNA-binding activity.<ref name="pmid15044251">{{cite journal |vauthors=Guiter C, Dusanter-Fourt I, Copie-Bergman C, Boulland ML, Le Gouvello S, Gaulard P, Leroy K, Castellano F |title=Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma |journal=Blood |volume=104 |issue=2 |pages=543–9 |date=July 2004 |pmid=15044251 |doi=10.1182/blood-2003-10-3545 |url=}}</ref>
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| * [[STAT6]] [[phosphorylation]] activates [[Interleukin 4]]/ [[Interleukin 13|interleukin-13]] signalling pathway.
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| * Constitutive [[STAT6]] [[phosphorylation]] and DNA-binding activity is detected is proved through [[immunohistochemical]] analysis.
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| * Another proposed mechanism of [[Autocrine signalling|autocrine]] pathway is [[amplification]] of [[JAK2|JAK 2]] pathway which causes [[phosphorylation]] of [[IL-4]] and [[IL-13]] subsequently.
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| * The [[Janus kinase]] 2 (JAK2) is also constitutively [[Phosphorylation|phosphorylated]] in the primary mediastinal large B-cell lymphoma.
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| * 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.
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| ===Genetics:=== | | ==[[Primary mediastinal large B-cell lymphoma pathophysiology|Pathophysiology]]== |
| * Genes involved in the pathogenesis of primary mediastinal large B-cell lymphoma include:
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| ** Comparative genomic hybridzation demonstrated gains in chromosome 9p24 and 2p15
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| ** Genomic hybridization in chromosome X-p11.4-21
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| ** [[Translocations]] involving the CIITA gene<ref name="pmid21368758">{{cite journal |vauthors=Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD |title=MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers |journal=Nature |volume=471 |issue=7338 |pages=377–81 |date=March 2011 |pmid=21368758 |pmc=3902849 |doi=10.1038/nature09754 |url=}}</ref>
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| ** [[Amplification]] of the [[REL]] [[oncogene]]<ref name="pmid8608249">{{cite journal |vauthors=Joos S, Otaño-Joos MI, Ziegler S, Brüderlein S, du Manoir S, Bentz M, Möller P, Lichter P |title=Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene |journal=Blood |volume=87 |issue=4 |pages=1571–8 |date=February 1996 |pmid=8608249 |doi= |url=}}</ref>
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| ** 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<ref name="pmid24497532">{{cite journal |vauthors=Twa DD, Chan FC, Ben-Neriah S, Woolcock BW, Mottok A, Tan KL, Slack GW, Gunawardana J, Lim RS, McPherson AW, Kridel R, Telenius A, Scott DW, Savage KJ, Shah SP, Gascoyne RD, Steidl C |title=Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma |journal=Blood |volume=123 |issue=13 |pages=2062–5 |date=March 2014 |pmid=24497532 |doi=10.1182/blood-2013-10-535443 |url=}}</ref>
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| ** The B cell leukemia/lymphoma 2 ([[Bcl-2|BCL-2]]) gene and B cell leukemia 6 ([[BCL-6 corepressor|BCL-6]]) gene rearrangements can occur.<ref name="pmid2788371">{{cite journal |vauthors=Lamarre L, Jacobson JO, Aisenberg AC, Harris NL |title=Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases |journal=Am. J. Surg. Pathol. |volume=13 |issue=9 |pages=730–9 |date=September 1989 |pmid=2788371 |doi= |url=}}</ref>
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| ** Gains of the [[proto-oncogene]] BCL11A and nuclear accumulation of BCL11A(XL) protein.<ref name="pmid16871282">{{cite journal |vauthors=Weniger MA, Pulford K, Gesk S, Ehrlich S, Banham AH, Lyne L, Martin-Subero JI, Siebert R, Dyer MJ, Möller P, Barth TF |title=Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11A(XL) protein are frequent in primary mediastinal B-cell lymphoma |journal=Leukemia |volume=20 |issue=10 |pages=1880–2 |date=October 2006 |pmid=16871282 |doi=10.1038/sj.leu.2404324 |url=}}</ref>
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| ** [[Immunoglobulin]] genes clonally rearranged.
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| ===Immunophenotype:=== | | ==[[Primary mediastinal large B-cell lymphoma causes|Causes]]== |
| * The [[immunophenotype]] of primary mediastinal large B-cell lymphoma is determined by [[histochemistry]] or [[flow cytometry]].
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| * The tumor cells express B cell-associated antigens ([[CD19]], [[CD20]], [[CD22]], [[CD79a]]) and [[CD45]].<ref name="pmid2788371">{{cite journal |vauthors=Lamarre L, Jacobson JO, Aisenberg AC, Harris NL |title=Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases |journal=Am. J. Surg. Pathol. |volume=13 |issue=9 |pages=730–9 |date=September 1989 |pmid=2788371 |doi= |url=}}</ref>
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| * Weak expression of [[CD30]] is often present.
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| * The [[tumor]] cells also stain for [[TRAF1|TRAF-1]] and [[REL|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]]. <ref name="pmid15644776">{{cite journal |vauthors=Rodig SJ, Savage KJ, Nguyen V, Pinkus GS, Shipp MA, Aster JC, Kutok JL |title=TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas |journal=Am. J. Surg. Pathol. |volume=29 |issue=2 |pages=196–203 |date=February 2005 |pmid=15644776 |doi= |url=}}</ref>
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| * Other markers that are relatively specific for primary mediastinal large B-cell lymphoma are [[CD200]] and [[MAL2 (gene)|MAL]].<ref name="pmid22899296">{{cite journal |vauthors=Dorfman DM, Shahsafaei A, Alonso MA |title=Utility of CD200 immunostaining in the diagnosis of primary mediastinal large B cell lymphoma: comparison with MAL, CD23, and other markers |journal=Mod. Pathol. |volume=25 |issue=12 |pages=1637–43 |date=December 2012 |pmid=22899296 |doi=10.1038/modpathol.2012.129 |url=}}</ref><ref name="pmid12429796">{{cite journal |vauthors=Copie-Bergman C, Plonquet A, Alonso MA, Boulland ML, Marquet J, Divine M, Möller P, Leroy K, Gaulard P |title=MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas |journal=Mod. Pathol. |volume=15 |issue=11 |pages=1172–80 |date=November 2002 |pmid=12429796 |doi=10.1097/01.MP.0000032534.81894.B3 |url=}}</ref>
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| ===Microscopic Pathology:===
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| * On microscopic [[histopathological]] analysis, large-sized cells and alveolar [[fibrosis]] are characteristic findings of primary mediastinal large B-cell lymphoma.
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| * The tumor is composed of large cells with variable [[nuclear]] features, cells may resemble:<ref name="pmid16129841">{{cite journal |vauthors=De Paepe P, Achten R, Verhoef G, Wlodarska I, Stul M, Vanhentenrijk V, Praet M, De Wolf-Peeters C |title=Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas |journal=J. Clin. Oncol. |volume=23 |issue=28 |pages=7060–8 |date=October 2005 |pmid=16129841 |doi=10.1200/JCO.2005.15.503 |url=}}</ref><ref name="canadiancancer">Primary mediastinal large B-cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-mediastinal-large-b-cell-lymphoma/?region=nb. Accessed on March 7, 2016 </ref>
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| ** [[Centroblastic and centrocytic lymphoma|Centroblasts]]
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| ** Large centrocytes
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| ** Multilobated cells, often with pale or "clear" [[cytoplasm]]
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| ** Less frequently, the tumor cells resemble [[Immunoblast|immunoblasts]]
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| ** Reed-Sternberg-like cells
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| ** Some cases have also presented with fine, compartmentalizing sclerosis.
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| <gallery widths="150" mode="packed" heights="150" perrow="3" showfilename="yes">
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| File:Primary mediastinal large B-cell lymphoma pathology .jpg
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| File:Primary medistinal large b-cell lymphoma pathology 1 .jpg
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| File:Primary mediastinal large B-cell lymphoma pathology 2.jpg|Primary mediastinal large B-cell lymphoma immunoreactivity for CD30<ref name="hindawi">Primary mediastinal large B-cell lymphoma.Hindawi Publishing Corporation. http://www.hindawi.com/journals/crihem/2012/197347/. Accessed on March 07, 2016 </ref>
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| </gallery>
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| ==Causes== | | ==[[Primary mediastinal large B-cell lymphoma differential diagnosis|Differentiating Primary mediastinal large B-cell lymphoma from other Diseases]]== |
| * There are no established causes of primary mediastinal B-cell lymphoma.
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| ==Differentiating ((Page name)) from Other Diseases== | | ==[[Primary mediastinal large B-cell lymphoma epidemiology and demographics|Epidemiology and Demographics]]== |
| * Primary mediastinal large B-cell lymphoma must be differentiated from other diseases such as:
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| ** [[Thymoma]]
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| ** [[Hodgkin's lymphoma]]
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| ** [[Thymic carcinoma]]
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| ==Epidemiology and Demographics== | | ==[[Primary mediastinal large B-cell lymphoma risk factors|Risk Factors]]== |
| * Primary mediastinal large B-cell lymphoma comprises of 7% of overall diffuse [[Diffuse large B cell lymphoma|large B cell lymphoma]]'s and 2.4 % of all [[Non-Hodgkin lymphoma|Non hodgkin lymphoma]]<nowiki/>s. <ref name="pmid9166827">{{cite journal |vauthors= |title=A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project |journal=Blood |volume=89 |issue=11 |pages=3909–18 |date=June 1997 |pmid=9166827 |doi= |url=}}</ref>
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| === Age: === | | ==[[Primary mediastinal large B-cell lymphoma screening|Screening]]== |
| * The incidence of primary mediastinal large B-cell lymphoma increases with age; the median age at diagnosis is 35 years.<ref name="pmid10889382" />
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| === Gender: === | | ==[[Primary mediastinal large B-cell lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| * Females are more commonly affected with primary mediastinal large B-cell lymphoma than males.<ref name="pmid10889382">{{cite journal |vauthors=Nguyen LN, Ha CS, Hess M, Romaguera JE, Manning JT, Cabanillas F, Cox JD |title=The outcome of combined-modality treatments for stage I and II primary large B-cell lymphoma of the mediastinum |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=47 |issue=5 |pages=1281–5 |date=July 2000 |pmid=10889382 |doi= |url=}}</ref>
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| ==Risk Factors==
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| * There are no established risk factors for primary mediastinal large B-cell lymphoma.
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| ==Screening==
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| * 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.<ref name="uspreventive">Recommendations. U.S Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=Primary+mediastinal+large+B-cell+lymphoma+. Accessed on March 7, 2016</ref>
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| ==Natural History, Complications, and Prognosis==
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| * Primary mediastinal large B-cell lymphoma is usually a fast-growing [[lymphoma]].
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| * Patients often have localized disease in the [[chest]] at first.
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| * If left untreated, primary mediastinal large B-cell lymphoma can cause:
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| ** [[shortness of breath]]
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| ** [[cough]]
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| ** [[chest pain]]
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| * 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]].
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| === '''Common complications''' : ===
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| * Compression of vessels in the neck often causes following symptoms :
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| ** [[Dyspnea]]
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| ** Facial swelling
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| ** Fullness of head on bending forwards
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| ** [[Arm]] swelling
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| ** [[Dysphagia]]
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| ** [[Cerebral edema]]
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| ** [[Headache]]
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| ** [[Confusion]]
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| ** [[Coma]]
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| * Potential [[Oncologic]] emergencies are:
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| ** Acute airway obstruction
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| ** [[Pericardial tamponade]]
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| ** [[Thrombosis]] of major neck or superior [[thoracic]] veins
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| * Patients with large [[Mediastinal mass|mediastinal masses]] are at increased risk of [[respiratory]] or [[cardiac arrest]] during [[general anesthesia]] or heavy [[sedation]].
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| * Patients who present with [[Cardiorespiratory arrest|cardiorespiratory symptoms]] or [[radiographic]] evidence of tracheal obstruction are at greatest risk of [[perioperative]] respiratory morbidity.
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| === '''Less common complication :''' ===
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| * Less common complication includes:
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| ** [[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]].
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| ** Deposition of [[uric acid]] and/or [[calcium phosphate]] crystals in the [[renal tubules]] results in [[acute renal failure]].
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| * The [[bone marrow]] is rarely affected by this type of lymphoma.
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| * Recurrence or relapse often occurs in organs or tissues outside the lymph nodes (extranodal sites), such as the [[kidneys]] or [[central nervous system]].
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| === '''Prognosis:''' ===
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| * 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]].
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| * Initial studies suggest that a more favorable course may be predicted by one of the following :
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| ** 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. <ref name="pmid24799481">{{cite journal |vauthors=Martelli M, Ceriani L, Zucca E, Zinzani PL, Ferreri AJ, Vitolo U, Stelitano C, Brusamolino E, Cabras MG, Rigacci L, Balzarotti M, Salvi F, Montoto S, Lopez-Guillermo A, Finolezzi E, Pileri SA, Davies A, Cavalli F, Giovanella L, Johnson PW |title=[18F]fluorodeoxyglucose positron emission tomography predicts survival after chemoimmunotherapy for primary mediastinal large B-cell lymphoma: results of the International Extranodal Lymphoma Study Group IELSG-26 Study |journal=J. Clin. Oncol. |volume=32 |issue=17 |pages=1769–75 |date=June 2014 |pmid=24799481 |doi=10.1200/JCO.2013.51.7524 |url=}}</ref>
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| ** Further study is needed to confirm the prognostic value of [[Positron emission tomography|PET]] before it can be used to modify initial treatment plans.
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| ==Diagnosis== | | ==Diagnosis== |
| ===Diagnostic Study of Choice===
| | [[Primary mediastinal large B-cell lymphoma diagnostic study of choice|Diagnostic study of choice]] | [[Primary mediastinal large B-cell lymphoma history and symptoms|History and Symptoms]] | [[Primary mediastinal large B-cell lymphoma physical examination|Physical Examination]] | [[Primary mediastinal large B-cell lymphoma laboratory findings|Laboratory Findings]] | [[Primary mediastinal large B-cell lymphoma electrocardiogram|Electrocardiogram]] | [[Primary mediastinal large B-cell lymphoma x ray|X-Ray Findings]] | [[Primary mediastinal large B-cell lymphoma echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Primary mediastinal large B-cell lymphoma CT scan|CT-Scan Findings]] | [[Primary mediastinal large B-cell lymphoma MRI|MRI Findings]] | [[Primary mediastinal large B-cell lymphoma other imaging findings|Other Imaging Findings]] | [[Primary mediastinal large B-cell lymphoma other diagnostic studies|Other Diagnostic Studies]] |
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| ===Biopsy:===
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| * The diagnosis of primary mediastinal large B cell lymphoma relies on the exclusion of adequate tissue, which offers most difficulty due to the location of the tumor, therefore an [[excisional biopsy]] is usually not possible.
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| * Therefore, surgical biopsy is highly preferred.<ref name="pmid19890836">{{cite journal |vauthors=Sun W, Song K, Zervos M, Pass H, Cangiarella J, Bizekis C, Crawford B, Wang BY |title=The diagnostic value of endobronchial ultrasound-guided needle biopsy in lung cancer and mediastinal adenopathy |journal=Diagn. Cytopathol. |volume=38 |issue=5 |pages=337–42 |date=May 2010 |pmid=19890836 |doi=10.1002/dc.21195 |url=}}</ref>
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| * Due to [[fibrosis]], needle aspirates are often paucicellular and fail to provide information about the tissue.
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| * Small biopsies may be non-diagnostic because the lesion is not sampled adequately or because crush artifact or extensive [[necrosis]], [[fibrosis]], or [[cystic]] change obscures the diagnostic lesion.
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| * Similarly, core biopsies mostly contain fibrotic tissue or [[Tumor cell|tumor cells]] that are disrupted and not useful.
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| * To obtain sufficient tissue for biopsy , patients usually undergo either one of the following techniques:<ref name="pmid19890836">{{cite journal |vauthors=Sun W, Song K, Zervos M, Pass H, Cangiarella J, Bizekis C, Crawford B, Wang BY |title=The diagnostic value of endobronchial ultrasound-guided needle biopsy in lung cancer and mediastinal adenopathy |journal=Diagn. Cytopathol. |volume=38 |issue=5 |pages=337–42 |date=May 2010 |pmid=19890836 |doi=10.1002/dc.21195 |url=}}</ref>
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| ** Cervical [[mediastinoscopy]]
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| ** [[Anterior mediastinotomy]]
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| ** [[Thoracoscopy]]
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| ===Staging===
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| * Staging for primary mediastinal large B-cell lymphoma is provided in the following table:<ref>{{Cite journal| doi = 10.1200/JCO.2013.54.8800| issn = 1527-7755| volume = 32| issue = 27| pages = 3059–3068| last1 = Cheson| first1 = Bruce D.| last2 = Fisher| first2 = Richard I.| last3 = Barrington| first3 = Sally F.| last4 = Cavalli| first4 = Franco| last5 = Schwartz| first5 = Lawrence H.| last6 = Zucca| first6 = Emanuele| last7 = Lister| first7 = T. Andrew| last8 = Alliance, Australasian Leukaemia and Lymphoma Group| last9 = Eastern Cooperative Oncology Group| last10 = European Mantle Cell Lymphoma Consortium| last11 = Italian Lymphoma Foundation| last12 = European Organisation for Research| last13 = Treatment of Cancer/Dutch Hemato-Oncology Group| last14 = Grupo Español de Médula Ósea| last15 = German High-Grade Lymphoma Study Group| last16 = German Hodgkin's Study Group| last17 = Japanese Lymphorra Study Group| last18 = Lymphoma Study Association| last19 = NCIC Clinical Trials Group| last20 = Nordic Lymphoma Study Group| last21 = Southwest Oncology Group| last22 = United Kingdom National Cancer Research Institute| title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification| journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology| date = 2014-09-20| pmid = 25113753}}</ref>
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| {| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
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| |+ '''Revised staging system for primary nodal lymphomas (Lugano classification)'''
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| ! style="background: #4479BA; color:#FFF;" | Stage
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| ! style="background: #4479BA; color:#FFF;" | Involvement
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| ! style="background: #4479BA; color:#FFF;" | Extranodal (E) status
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| |-
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| | colspan="3" style="padding: 5px 5px; background: #DCDCDC;" | '''Limited'''
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| |-
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| | style="padding: 5px 5px; background: #F5F5F5;" | Stage I
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| | style="padding: 5px 5px; background: #F5F5F5;" | One node or a group of adjacent nodes
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| | style="padding: 5px 5px; background: #F5F5F5;" | Single extranodal lesions without nodal involvement
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| |-
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| | style="padding: 5px 5px; background: #F5F5F5;" | Stage II
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| | style="padding: 5px 5px; background: #F5F5F5;" | Two or more nodal groups on the same side of the diaphragm
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| | style="padding: 5px 5px; background: #F5F5F5;" | Stage I or II by nodal extent with limited contiguous extranodal involvement
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| |-
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| | style="padding: 5px 5px; background: #F5F5F5;" | Stage II bulky
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| | style="padding: 5px 5px; background: #F5F5F5;" | II as above with "bulky" disease
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| | style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
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| |-
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| | colspan="3" style="padding: 5px 5px; background: #DCDCDC;" | '''Advanced'''
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| |-
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| | style="padding: 5px 5px; background: #F5F5F5;" | Stage III
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| | style="padding: 5px 5px; background: #F5F5F5;" | Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
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| | style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
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| |-
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| | style="padding: 5px 5px; background: #F5F5F5;" | Stage IV | |
| | style="padding: 5px 5px; background: #F5F5F5;" | Additional noncontiguous extralymphatic involvement
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| | style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
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| |}
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| ===History and Symptoms===
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| Symptoms of the primary mediastinal large B-cell lymphoma include:
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| * [[Fever]]
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| * [[Weight loss]]
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| * [[Night sweats]]
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| * [[Skin rash]]
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| * [[Shortness of breath]]
| |
| * [[Facial swelling]]
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| * [[Cough]]
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| * Painless swelling in the [[neck]], [[axilla]], [[groin]], [[thorax]], and abdomen
| |
| | |
| === Physical Examination ===
| |
| | |
| ==== Vitals ====
| |
| * [[Fever]] is often present
| |
| | |
| ==== Skin ====
| |
| * [[Rash]]
| |
| | |
| ==== HEENT ====
| |
| * [[Lymphadenopathy|Cervical lymphadenopathy]]
| |
| * Facial edema
| |
| | |
| ==== Thorax ====
| |
| * Thoracic masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
| |
| * Localized anterosuperior mediastinal mass
| |
| | |
| ==== Abdomen ====
| |
| * [[Abdominal mass|Abdominal masses]] suggestive of [[Lymphadenopathy|central lymphadenopathy]]
| |
| | |
| ==== Extremities ====
| |
| * [[Lymphadenopathy|Peripheral lymphadenopathy]]
| |
| | |
| === Laboratory Findings ===
| |
| Laboratory tests for primary mediastinal large B-cell lymphoma include:
| |
| * [[Complete blood count]] (CBC)
| |
| * Blood chemistry studies
| |
| * Liver function tests
| |
| * Serum LDH levels
| |
| * Beta 2 microglobulin levels
| |
| * Cytogenetic analysis
| |
| * [[Flow cytometry]]
| |
| * [[Immunohistochemistry]]
| |
| * [[Immunophenotyping]]
| |
| ** Positive: [[CD19]], [[CD79a]], [[CD20]], [[CD30]], and [[CD22]]
| |
| | |
| ===Electrocardiogram===
| |
| * There are no ECG findings associated with primary mediastinal large B-cell lymphoma.
| |
| | |
| ====Chest X-Ray====
| |
| * Chest X-ray may be helpful in the diagnosis of primary mediastinal large B-cell lymphoma. Finding on chest X-ray suggestive of primary mediastinal large B-cell lymphoma includes large anterior mediastinal mass.<ref name="hindawi">Primary mediastinal large B-cell lymphoma.Hindawi Publishing Corporation. http://www.hindawi.com/journals/crionm/2013/814291/. Accessed on March 07, 2016 </ref>
| |
| {| align="right"
| |
| | | |
| [[File:Primary mediastinal-lymphoma-large-b-cell-1.jpg|200px|thumb|An Xray showing mediastinal large B-cell lymphoma.[https://radiopaedia.org/cases/mediastinal-lymphoma-large-b-cell-1 Source: Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 8655]]] | |
| |} | |
| ====Biopsy====
| |
| * Lymph node or mediastinal mass biopsy is diagnostic of primary mediastinal large B-cell lymphoma.
| |
| | |
| ====Echocardiography====
| |
| * Echocardiography may be helpful in the diagnosis of primary mediastinal large B-cell lymphoma.
| |
| ====CT ====
| |
| [[CT]] scan may be helpful in the diagnosis of primary mediastinal large B-cell lymphoma.
| |
| {| align="right"
| |
| | | |
| [[File:Ct scan showing primary mediastinal large B-cell lymphoma.gif|200px|thumb| CT scan of Femur showing giant cell tumor. [https://radiopaedia.org/cases/mediastinal-lymphoma-large-b-cell-1|Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 8655]]] | |
| |} | |
| | |
| ==== MRI ====
| |
| [[MRI]] scan may be helpful in the diagnosis of primary mediastinal large B-cell lymphoma. | |
| <gallery widths="150">
| |
| File:Primary medistinal large B-cell lymphoma MRI .jpg|Cardiac MRI short axis T1 at the level of mitral valve reveals a large mediastinal mass infiltrating and obliterating the SVC causing SVC obstruction. The tumor extends into the right atrium (red arrow) and invades the tricuspid valve.<ref name="hindawi">Primary mediastinal large B-cell lymphoma.Hindawi Publishing Corporation. http://www.hindawi.com/journals/crionm/2013/814291/. Accessed on March 07, 2016 </ref>
| |
| </gallery>
| |
| | |
| ==== Other Imaging Findings ====
| |
| * [[PET]] scan may be helpful in the diagnosis of primary mediastinal large B-cell lymphoma.
| |
| * In contrast to [[CT]] imaging, [[FDG-PET]] is a functional imaging tool that can distinguish between viable tumor and [[necrosis]] or [[fibrosis]] in a residual mass.<ref name="pmid25205600">{{cite journal |vauthors=Nagle SJ, Chong EA, Chekol S, Shah NN, Nasta SD, Glatstein E, Plastaras JP, Torigian DA, Schuster SJ, Svoboda J |title=The role of FDG-PET imaging as a prognostic marker of outcome in primary mediastinal B-cell lymphoma |journal=Cancer Med |volume=4 |issue=1 |pages=7–15 |date=January 2015 |pmid=25205600 |pmc=4312112 |doi=10.1002/cam4.322 |url=}}</ref>
| |
| ===Other diagnostic studies===
| |
| | |
| * Monoclonal anti-MAL antibody is now commercially used in order to identify primary mediastinal large B-cell lymphoma. It provides good [[sensitivity]] and high [[specificity]] for diagnosis of primary mediastinal large B-cell lymphoma. <ref name="pmid16224207">{{cite journal |vauthors=Traverse-Glehen A, Pittaluga S, Gaulard P, Sorbara L, Alonso MA, Raffeld M, Jaffe ES |title=Mediastinal gray zone lymphoma: the missing link between classic Hodgkin's lymphoma and mediastinal large B-cell lymphoma |journal=Am. J. Surg. Pathol. |volume=29 |issue=11 |pages=1411–21 |date=November 2005 |pmid=16224207 |doi= |url=}}</ref>
| |
|
| |
|
| ==Treatment== | | ==Treatment== |
| ===Medical Therapy===
| | [[Primary mediastinal large B-cell lymphoma medical therapy|Medical Therapy]] | [[Primary mediastinal large B-cell lymphoma surgery|Surgery]] | [[Primary mediastinal large B-cell lymphoma primary prevention|Primary Prevention]] | [[Primary mediastinal large B-cell lymphoma secondary prevention|Secondary Prevention]] | [[Primary mediastinal large B-cell lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Primary mediastinal large B-cell lymphoma future or investigational therapies|Future or Investigational Therapies]] |
| | |
| {| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
| |
| |+ '''Treatment of primary mediastinal large B-cell lymphoma<ref name="canadiancancer">Primary mediastinal large B-cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-mediastinal-large-b-cell-lymphoma/?region=nb. Accessed on March 7, 2016 </ref>'''
| |
| ! style="background: #4479BA; color:#FFF;" | Therapy
| |
| ! style="background: #4479BA; color:#FFF;" | Description
| |
| |-
| |
| |-
| |
| | style="padding: 5px 5px; background: #DCDCDC;" | [[Chemotherapy]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" |
| |
| * A commonly used combination chemotherapy is CHOP: [[Cyclophosphamide]], [[Doxorubicin]], [[Vincristine]], {{and}} [[Prednisone]]
| |
| |-
| |
| | style="padding: 5px 5px; background: #DCDCDC;" | [[Biological therapy]] | |
| | style="padding: 5px 5px; background: #F5F5F5;" | | |
| * [[Rituximab]] may be added to chemotherapy.
| |
| |-
| |
| | style="padding: 5px 5px; background: #DCDCDC;" | [[Radiation therapy]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" |
| |
| * [[External beam radiation therapy]] to the mass in the chest may be used after chemotherapy.
| |
| |-
| |
| | style="padding: 5px 5px; background: #DCDCDC;" | [[Stem cell transplant]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" | | |
| * A [[stem cell transplant]] may be offered to some people if their lymphoma returns or relapses after treatment.
| |
| |} | |
| * The choice of initial treatment depends on stage of disease at the time of presentation. Following are different treatment regimens that are recommended for various stages:
| |
| | |
| ===Induction Chemotherapy:===
| |
| * [[R-CHOP]] [[chemotherapy]] which includes [[rituximab]], [[cyclophosphamide]], [[doxorubicin]], [[vincristine]], [[prednisone]] is preferred regimen for limited disease but it is not suggested alone, follow up with [[radiotherapy]] is highly recommended to prevent relapse of disease.
| |
| * Dose adjusted da-EPOCH-Retoposide, [[doxorubicin]], [[cyclophosphamide]], [[vincristine]], [[prednisone]], and [[rituximab]].
| |
| ** This is best for the patients who wish to avoid radiotherapy, such as young patients (<30 yrs) or women who have concerns with irradiation of breast tissue.
| |
| * However investigators from Europe have suggested that MACOP-B([[methotrexate]] with [[leucovorin]] rescue, [[doxorubicin]], [[cyclophosphamide]], [[vincristine]], [[prednisone]], and [[bleomycin]]) may be superior to CHOP in the management of primary mdiastinal large B-cell lymphoma.
| |
| ===Radiotherapy:===
| |
| * [[Radiotherapy]] is usually indicated to prevent relapse and recurrence of disease after [[chemotherapy]] induction especially after following R-CHOP regimen.<ref name="pmid24799481">{{cite journal |vauthors=Martelli M, Ceriani L, Zucca E, Zinzani PL, Ferreri AJ, Vitolo U, Stelitano C, Brusamolino E, Cabras MG, Rigacci L, Balzarotti M, Salvi F, Montoto S, Lopez-Guillermo A, Finolezzi E, Pileri SA, Davies A, Cavalli F, Giovanella L, Johnson PW |title=[18F]fluorodeoxyglucose positron emission tomography predicts survival after chemoimmunotherapy for primary mediastinal large B-cell lymphoma: results of the International Extranodal Lymphoma Study Group IELSG-26 Study |journal=J. Clin. Oncol. |volume=32 |issue=17 |pages=1769–75 |date=June 2014 |pmid=24799481 |doi=10.1200/JCO.2013.51.7524 |url=}}</ref>
| |
| * In aggressive disease, [[radiation therapy]] has been proven to be beneficial in patients with good-prognosis stage I and nonbulky stage II disease.<ref name="pmid9647875">{{cite journal |vauthors=Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI |title=Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma |journal=N. Engl. J. Med. |volume=339 |issue=1 |pages=21–6 |date=July 1998 |pmid=9647875 |doi=10.1056/NEJM199807023390104 |url=}}</ref>
| |
| ===High-Dose Chemotherapy and Autologous Stem Cell Transplantation:===
| |
| * The use of high-dose [[chemotherapy]] and [[autologous stem cell transplantation]] in patients with aggressive disease proves to be beneficial in some cases.<ref name="pmid9060555">{{cite journal |vauthors=Haioun C, Lepage E, Gisselbrecht C, Bastion Y, Coiffier B, Brice P, Bosly A, Dupriez B, Nouvel C, Tilly H, Lederlin P, Biron P, Brière J, Gaulard P, Reyes F |title=Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte |journal=J. Clin. Oncol. |volume=15 |issue=3 |pages=1131–7 |date=March 1997 |pmid=9060555 |doi=10.1200/JCO.1997.15.3.1131 |url=}}</ref>
| |
| ===Relapsed disease:===
| |
| * Patients with relapsed disease often have [[systemic involvement]] and many also have [[extranodal]] diseas, in the [[parenchymal organs]], including [[kidneys]], [[liver]], and [[CNS]].<ref name="pmid10561185">{{cite journal |vauthors=Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP |title=Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group |journal=J. Clin. Oncol. |volume=17 |issue=4 |pages=1244 |date=April 1999 |pmid=10561185 |doi=10.1200/JCO.1999.17.4.1244 |url=}}</ref>
| |
| * These patients are recommended to undergo salvage systemic chemotherapy followed by [[stem cell transplantation]].<ref name="pmid9440724">{{cite journal |vauthors=Popat U, Przepiork D, Champlin R, Pugh W, Amin K, Mehra R, Rodriguez J, Giralt S, Romaguera J, Rodriguez A, Preti A, Andersson B, Khouri I, Claxton D, de Lima M, Donato M, Anderlini P, Gajewski J, Cabanillas F, van Besien K |title=High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome |journal=J. Clin. Oncol. |volume=16 |issue=1 |pages=63–9 |date=January 1998 |pmid=9440724 |doi=10.1200/JCO.1998.16.1.63 |url=}}</ref>
| |
| | |
| === '''Salvage therapy:''' ===
| |
| * [[rituximab]], [[ifosfamide]], [[carboplatin]], and [[etoposide]] (RICE) serves as a salvage approach.
| |
| * Patients who demonstrate improvement on [[PET scan|PET]] scan are recommended for transplantation.
| |
| * Patients who have refractory disease should be offered clinical trials, although some can be considered for [[allogeneic bone marrow transplantation]].
| |
| | |
| ==Surgery==
| |
| * Surgical intervention is not recommended for the management of primary mediastinal large B-cell lymphoma.
| |
| | |
| ==Primary Prevention==
| |
| * There are no established measures for the primary prevention of primary mediastinal large B-cell lymphoma.
| |
| | |
| ==Secondary Prevention==
| |
| * There are no established measures for the secondary prevention of primary mediastinal large B-cell lymphoma.
| |
|
| |
|
| ==References== | | ==Case Studies== |
| {{Reflist|2}}
| | [[rimary mediastinal large B-cell lymphoma case study one|Case #1]] |
|
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| [[Category:Disease]] | | [[Category: (oncology)]] |
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| [[Category:Immunology]]
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