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    Lymphomatoid Granulomatosis Variant of Diffuse Large B Cell Lymphoma

    Definition

    • Angiocentric and angiodestructive lymphoproliferative disorder predominantly composed of large atypical EBV positive B cells

    Alternate/Historical Names

    • Polymorphic reticulosis
    • Angiocentric immunoproliferative lesion
    • Malignant angiitis
    • Malignant granulomatosis
    • Angiocentric lymphoma

    Diagnostic Criteria

    • Angiocentric and angiodestructive lymphoid infiltrate
    • EBV positive B cells
      • Must be predominiant population
      • May form confluent sheets
    • Prominent population of reactive T cells
    • Extensive necrosis
    • Virtually all cases involve lung
      • Multiple pulmonary nodules
      • Skin involved in nearly half of cases
        • Dermal and subcutaneous nodules show similar features to lung
        • May show nonspecific plaque like dermal infiltrate
      • CNS and kidney also frequently involved
    • If atypical cells are rare or only occasional, designate as Grade I or Low Grade Lymphomatoid Granulomatosis

    Yasodha Natkunam MD PhD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting:: May 1, 2006

    Supplemental studies

    Immunohistology

    • Large atypical cells
      • B lineage (CD20, CD79a+)
      • EBV LMP positive but much less reliable than in situ hybridization
    • Small cells
      • T cell phenotype
      • May be predominant population

    Genetic analysis

    • EBV EBER positive by in situ hybridization
      • Required for diagnosis

    Differential Diagnosis

    Post-transplant Lymphoproliferative Disorder Lymphomatoid Granulomatosis or Lymphomatoid Granulomatosis Lymphoma
    T cell poor infiltrate T cell rich infiltrate
    Not angiocentric Angiocentric
    Definitionally post-transplant Rare cases post-transplant
    Both contain EBV+ B cells
    The distinction may sometimes be arbitrary

    Wegener Granulomatosis Lymphomatoid Granulomatosis or Lymphomatoid Granulomatosis Lymphoma
    No prominent lymphoid infiltrate Prominent lymphoid infiltrate
    Neutrophilic microabscesses No abscesses
    EBV negative EBV+ B cell population
    Both are angiocentric

    Extranodal NK/T Cell Lymphoma, Nasal Type Lymphomatoid Granulomatosis or Lymphomatoid Granulomatosis Lymphoma
    Atypical cells are CD56+ cytotoxic T cells Atypical cells are B cells
    Both may involve ENT sites and lung, are angiocentric, necrotizing and are EBV+

    Hodgkin Lymphoma Lymphomatoid Granulomatosis or Lymphomatoid Granulomatosis Lymphoma
    CD15 80% CD15 negative
    CD20 or CD79a 20% CD20 or CD79a 100%
    Background with neutrophils, eosinophils, plasma cells Background of small T cells
    Rare in lung and skin Typically involves lung and skin
    Both may be necrotizing, CD30+ and EBV+

    Diffuse Large B Cell Lymphoma, NOS Lymphomatoid Granulomatosis Lymphoma
    EBV negative EBV positive
    Not angiocentric Angiocentric and angiodestructive
    Prominent T cell infiltrate only in T Cell Rich Variant Prominent T cell infiltrate

    Clinical

    • Virtually all cases involve lung at some point in disease
      • Multiple lung nodules common
      • Skin involved in 40-50% of cases
      • CNS, kidney, GI tract, head and neck also frequently involved
    • Lymphoid organs involved only in late disease
    • Most common in forties but wide age range
    • Some cases reported associated with HIV or organ transplantation immunosuppression
    • Poor prognosis

    Grading / Staging / Report

    Grade III or High Grade in the following Lymphomatoid Granulomatosis grading systems corresponds to lymphoma

    Three tier system

    • Grade I
      • No large atypical cells
      • Little necrosis
      • EBV in situ+ cells rare
      • Some cases spontaneously resolve
    • Grade II
      • Occasional large atypical cells
      • Moderate necrosis
      • EBV in situ+ cells 5-20/hpf
      • Some cases spontaneously resolve
    • Grade III
      • Predomiant population of large atypical cells
        • May be confluent
      • Extensive necrosis

    Two tier grading system favored by some over original three tier system

    • Low grade
      • Few large atypical cells
      • Few mitotic figures
      • Little necrosis
      • Some cases spontaneously resolve
    • High grade
      • Predomiant population of large atypical cells
      • Extensive necrosis

    Ann Arbor Staging System

    • Stage IV by definition
    • 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 eds. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2001
    • Colby TV, Koss MN, Travis WD. Tumors of the Lower Respiratory Tract, Atlas of Tumor Pathology, AFIP Tird Series, Fascicle 13, 1995
    • Beaty MW, Toro J, Sorbara L, Stern JB, Pittaluga S, Raffeld M, Wilson WH, Jaffe ES. Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features. Am J Surg Pathol. 2001 Sep;25(9):1111-20.
    • Jaffe ES, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv. 1997;30:233-48.
    • Guinee D Jr, Jaffe E, Kingma D, Fishback N, Wallberg K, Krishnan J, Frizzera G, Travis W, Koss M. Pulmonary lymphomatoid granulomatosis. Evidence for a proliferation of Epstein-Barr virus infected B-lymphocytes with a prominent T-cell component and vasculitis. Am J Surg Pathol. 1994 Aug;18(8):753-64.
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