Primary mediastinal large B cell lymphoma
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
- Jonathan W Friedberg, MD
Jonathan W Friedberg, MD
- Professor of Medicine
- James P Wilmot Cancer Center, University of Rochester
Primary mediastinal large B cell lymphoma (PMBL) is an aggressive B cell lymphoma that is thought to arise from thymic (medullary) B cells. It has clinicopathologic features that are distinct from systemic diffuse large B cell lymphoma (DLBCL) and shares some clinical and biologic features with classical nodular sclerosing Hodgkin lymphoma (HL).
This topic will discuss the clinical presentation, pathologic features, diagnosis, and treatment of PMBL. The diagnosis and treatment of systemic DLBCL and HL are presented separately. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma" and "Initial treatment of limited stage diffuse large B cell lymphoma" and "Overview of the treatment of classical Hodgkin lymphoma in adults".)
Primary mediastinal large B cell lymphoma (PMBL) comprises 7 percent of diffuse large B cell lymphomas (2.4 percent of all non-Hodgkin lymphomas) [1,2]. There is a female predominance and a median age at diagnosis in the third to fourth decade .
Oncologic emergencies — Patients present with a locally invasive anterior mediastinal mass originating in the thymus, with frequent airway compromise and superior vena cava (SVC) syndrome (image 1 and image 2) . In one report of 30 patients, for example, SVC syndrome was present in 57 percent at presentation . In addition, other patients without clinical SVC obstruction had evidence of compression of this vessel by computed tomography (CT) scan; in total, 80 percent had some evidence of SVC compromise. (See "Malignancy-related superior vena cava syndrome" and "Pathology of mediastinal tumors".)
Prompt recognition and management of SVC syndrome is critical. The clinical diagnosis of SVC syndrome is made on the basis of characteristic signs and symptoms of central venous obstruction. Dyspnea is the most common symptom. In addition, patients frequently complain of facial swelling or head fullness, which may be exacerbated by bending forward or lying down. Other symptoms include arm swelling, cough, chest pain, or dysphagia. Patients with cerebral edema may have headaches, confusion, or possibly coma. The diagnosis and management of malignancy-related SVC syndrome is presented separately. (See "Malignancy-related superior vena cava syndrome", section on 'Clinical manifestations and diagnosis'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997; 89:3909.
- Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998; 16:2780.
- Nguyen LN, Ha CS, Hess M, et al. The outcome of combined-modality treatments for stage I and II primary large B-cell lymphoma of the mediastinum. Int J Radiat Oncol Biol Phys 2000; 47:1281.
- van Besien K, Kelta M, Bahaguna P. Primary mediastinal B-cell lymphoma: a review of pathology and management. J Clin Oncol 2001; 19:1855.
- Jacobson JO, Aisenberg AC, Lamarre L, et al. Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy. Cancer 1988; 62:1893.
- Savage KJ, Al-Rajhi N, Voss N, et al. Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol 2006; 17:123.
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
- Tateishi U, Müller NL, Johkoh T, et al. Primary mediastinal lymphoma: characteristic features of the various histological subtypes on CT. J Comput Assist Tomogr 2004; 28:782.
- Addis BJ, Isaacson PG. Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin. Histopathology 1986; 10:379.
- Lamarre L, Jacobson JO, Aisenberg AC, Harris NL. Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases. Am J Surg Pathol 1989; 13:730.
- Rodig SJ, Savage KJ, Nguyen V, et al. TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas. Am J Surg Pathol 2005; 29:196.
- Dorfman DM, Shahsafaei A, Alonso MA. Utility of CD200 immunostaining in the diagnosis of primary mediastinal large B cell lymphoma: comparison with MAL, CD23, and other markers. Mod Pathol 2012; 25:1637.
- Copie-Bergman C, Plonquet A, Alonso MA, et al. MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Mod Pathol 2002; 15:1172.
- Steidl C, Shah SP, Woolcock BW, et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 2011; 471:377.
- Steidl C, Gascoyne RD. The molecular pathogenesis of primary mediastinal large B-cell lymphoma. Blood 2011; 118:2659.
- Möller P, Moldenhauer G, Momburg F, et al. Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation. Blood 1987; 69:1087.
- Scarpa A, Bonetti F, Menestrina F, et al. Mediastinal large-cell lymphoma with sclerosis. Genotypic analysis establishes its B nature. Virchows Arch A Pathol Anat Histopathol 1987; 412:17.
- Tsang P, Cesarman E, Chadburn A, et al. Molecular characterization of primary mediastinal B cell lymphoma. Am J Pathol 1996; 148:2017.
- Joos S, Otaño-Joos MI, Ziegler S, et al. Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood 1996; 87:1571.
- Twa DD, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood 2014; 123:2062.
- Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003; 198:851.
- Savage KJ, Monti S, Kutok JL, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003; 102:3871.
- Guiter C, Dusanter-Fourt I, Copie-Bergman C, et al. Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma. Blood 2004; 104:543.
- Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Sehn LH, Antin JH, Shulman LN, et al. Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. Blood 1998; 91:717.
- Hamlin PA, Portlock CS, Straus DJ, et al. Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999. Br J Haematol 2005; 130:691.
- Todeschini G, Ambrosetti A, Meneghini V, et al. Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients. J Clin Oncol 1990; 8:804.
- Haioun C, Gaulard P, Roudot-Thoraval F, et al. Mediastinal diffuse large-cell lymphoma with sclerosis: a condition with a poor prognosis. Am J Clin Oncol 1989; 12:425.
- Zinzani PL, Stefoni V, Finolezzi E, et al. Rituximab combined with MACOP-B or VACOP-B and radiation therapy in primary mediastinal large B-cell lymphoma: a retrospective study. Clin Lymphoma Myeloma 2009; 9:381.
- Pfreundschuh M, Trümper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006; 7:379.
- Pfreundschuh M, Kuhnt E, Trümper L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011; 12:1013.
- Rieger M, Osterborg A, Pettengell R, et al. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol 2011; 22:664.
- Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 2013; 368:1408.
- Wilson WH, Pittaluga S, Nicolae A, et al. A prospective study of mediastinal gray-zone lymphoma. Blood 2014; 124:1563.
- Martelli M, Ceriani L, Zucca E, et al. [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. J Clin Oncol 2014; 32:1769.
- Savage KJ, Yenson PR, Shenkier T, et al. The outcome of primary mediastinal large B-cell lymphoma (PMBCL) in the R-CHOP treatment era (abstract 303). Blood 2012; 120.
- Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007; 25:571.
- Kuruvilla J, Pintilie M, Tsang R, et al. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma 2008; 49:1329.
- Rodríguez J, Conde E, Gutiérrez A, et al. Primary mediastinal large cell lymphoma (PMBL): frontline treatment with autologous stem cell transplantation (ASCT). The GEL-TAMO experience. Hematol Oncol 2008; 26:171.
- Cairoli R, Grillo G, Tedeschi A, et al. Efficacy of an early intensification treatment integrating chemotherapy, autologous stem cell transplantation and radiotherapy for poor risk primary mediastinal large B cell lymphoma with sclerosis. Bone Marrow Transplant 2002; 29:473.
- Popat U, Przepiork D, Champlin R, et al. High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome. J Clin Oncol 1998; 16:63.
- Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood 2017; 130:267.
- Lazzarino M, Orlandi E, Paulli M, et al. Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients. J Clin Oncol 1997; 15:1646.
- Ceriani L, Martelli M, Zinzani PL, et al. Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma. Blood 2015; 126:950.
- CLINICAL PRESENTATION
- Oncologic emergencies
- Other signs and symptoms
- Radiographic features
- PATHOLOGIC FEATURES
- Genetic features
- Obtaining tissue
- Further evaluation
- Making the diagnosis
- DIFFERENTIAL DIAGNOSIS
- Systemic lymphoma with secondary mediastinal involvement
- Hodgkin lymphoma
- Pretreatment evaluation
- Initial therapy
- - Choice of therapy
- - Chemoimmunotherapy
- - Is radiation necessary?
- Evaluation of response
- Relapsed or refractory disease
- Clinical trials