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    Primary mediastinal (thymic) large B cell lymphoma

    Definition

    • Large B cell lymphoma primarily involving the mediastinum

    Alternate/Historical Names

    • Mediastinal large cell lymphoma with sclerosis
    • Mediastinal clear cell lymphoma

    Diagnostic Criteria

    • Primary site of involvement must be mediastinum
      • Other nodal and extranodal sites may be involved
    • Diffuse infiltration and sclerosis frequent
      • Frequent diffuse infiltration of mediastinal soft tissue and surrounding structures
        • Overrun thymus may be identifiable
        • Thymic epithelium may be hyperplastic or cystic
      • Sclerosis, necrosis and large vessel vascular invasion frequent
        • Primarily when extrathymic or extranodal
    • Wide range of nuclear features
      • May be even more variable than usual diffuse large B cell lymphoma
      • Cytoplasm variable but abundant and clear (retraction artifact) in about 40% of cases
      • Cytology does not correlate with behavior
    • B lineage required
      • Immunoglobulin frequently negative, even in frozen tissue or by flow, although immunoglobulin genes are rearranged

    John P Higgins MD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting:: March 8, 2005

    Supplemental studies

    Immunohistology

    • B lineage is required for diagnosis
      • CD20 and or CD79a pos
      • Immunoglobulin frequently negative, even with frozen tissue or on flow, although immunoglobulin genes are rearranged

      CD5 Neg
      CD10 33%
      bcl6 100%
      CD30 69%
      CD15 4%
    • Keratin may highlight overrun or hyperplastic thymus
      • Reported in 40% of cases with adequate tissue
    • HCG has been reported in one case
      • 10 other cases tested were negative

    Genetic Study

    • Immunoglobulin gene rearrangements are present, even in cases in which immunoglobulin is not demonstrable
    • Cytogenetics infrequently useful
      • Gains of chromosomal material are more common than losses
      • However, gain of chromosome 9p, seen in a minority of cases, is the only non-random karyotypic alteration

    Differential Diagnosis

     

    Classical Hodgkin lymphoma vs. Mediastinal Large B Cell Lymphoma

    • Nodular sclerosis Hodgkin lymphoma and mediastinal B cell lymphoma share features of age, location and sclerotic background and frequently have to be distinguished on the basis of small specimens
    • If the biopsy is large enough, the following features may be definitive for the diagnosis of NSHL
      • Nodular architecture
      • Polymorphous background
      • Cytologic features of RS cells
    • Most specimens will need immunohistochemical study as below
      • Note that in mediastinal B cell lymphoma, immunoglobulin staining is frequently negative, even in frozen tissue
      • Note that Reed Sternberg cells are frequently positive for both kappa and lambda, apparently due to nonspecific uptake of serum immunoglobulin.
      Classical Hodgkin Lymphoma Mediastinal B Cell Lymphoma
    CD20 20% >90%
    CD79a 10% >90%
    LCA/CD45RB 10% >90%
    CD15 80% 4%
    CD30 90% 69%
    Light chains polytypic or negative monotypic or negative

     

    Thymoma vs. Mediastinal B Cell Lymphoma

    • Sclerosis usually confined to thick bands and capsule
    • Thymic epithelial cells should be numerous
      • Keratin stain may be useful to highlight epithelial cells
        • However, we have occasionally found thymoma epithelial cells to stain only variably with common anti-keratin antibodies
      • Overrun or even hyperplastic thymic epithelial cells may be seen in lymphoma
      • Even distribution is more typical of thymoma
    • Immature T cells are numerous in most thymomas
      • CD1a, CD99 and TdT positive
    • CD20 may stain epithelial cells in Type A and Type AB thymomas
      • Positive cells are spindled
      • Keratin stains and other B lineage markers should resolve the diagnosis
    • Necrosis may be widespread in both thymoma and lymphoma

    Thymic carcinoma vs. Mediastinal B Cell Lymphoma

    • Keratin and CD20 should resolve the differential if lesional cells are present in specimen

    Sclerosing mediastinitis vs. Mediastinal B Cell Lymphoma

    • Sclerosing mediastinitis lacks the population of large atypical B cells of mediastinal B cell lymphoma

    Germ Cell Tumor vs. Mediastinal B Cell Lymphoma

    • Embryonal carcinoma and yolk sac tumor should be clearly keratin positive
      • AFP and HCG may be positive, but frequently negative
    • Seminoma is frequently negative for keratin
      • Look closely for punctate keratin staining
      • PLAP is variably positive in seminoma, uniformly negative in lymphoma
      • HCG may be positive if trophoblastic giant cells are present
    • Serum HCG or AFP may be positive in the absence of tissue section reactivity in germ cell tumors
    • B lineage markers and LCA should be negative in all germ cell tumors
    • Both embryonal carcinoma and mediastinal B cell lymphoma may be CD30 positive
    • One case of mediastinal lymphoma with HCG expression has been reported
    • Necrosis may be widespread in both germ cell tumors and lymphoma

    Clinical

    • Mean age 25-30 years but wide range
    • Female : Male 2:1
    • Frequent obstruction of superior vena cava or trachea
    • Frequent (26%) CNS involvement, primarily on relapse
    • Lamarre has suggested that there are two types of mediastinal B cell lymphoma
      • Immunoglobulin negative, predominantly female, younger
      • Immunoglobulin positive, no sex preference, older
    • The prognosis of primary mediastinal B cell lymphoma has been debated
      • Some series have found aggressive clinical behavior and a poor prognosis
      • Others indicate a similar prognosis to that of other non-mediastinal B cell lymphomas

    Grading / Staging / Report

    Grading is not applicable

    Ann Arbor Staging System

    • Stage I
      • I if involvement of a single lymph node region
      • IE if involvement of a single extralymphatic organ or site
    • Stage II
      • II if two or more lymph node regions on same side of diaphragm
      • IIE if localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm
    • Stage III
      • III if Involvement of lymph node regions on both sides of the diphragm
      • IIIS if spleen involved
      • IIIE if extralymphatic site involved
    • Stage IV
      • Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement
    • Systemic Symptoms in 6 months preceding admission
      • Fever, night sweats, 10% weight loss
      • A = absent
      • B = present
    • Extranodal sites are also designated
      • M+ = marrow
      • L+ = lung
      • H+ = liver
      • P+ = pleura
      • O+ = bone
      • D+ = skin and subcutaneous tissue
    • Although originally designed for Hodgkin lymphoma, the Ann Arbor System is also used for non-Hodgkin lymphomas.

    The pathology report should contain the following information:

    • Diagnosis in the World Health Organization (WHO) classification
      • Equivalent diagnosis in other classifications used by relevant clinicians
    • Results of supplementary studies if performed
    • Relationship to other specimens from the same patient
    • Information relevant to staging if available

    Lists

    Types and variants of large B cell lymphoma

    Bibliography

    • Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
    • Jaffe ES, Harris NL Stein H, Vardiman JW . Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2001
    • Higgins JPT and Warnke RA. CD30 Expression Is Common in Mediastinal Large B-Cell Lymphoma. Am J Clin Pathol. 1999 Aug;112(2):241-7.
    • Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d'Etude des Lymphomes de l'Adulte") study. Am J Surg Pathol. 1996;20: 877-888.
    Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
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