Lymphomatoid Granulomatosis

Lymphomatoid Granulomatosis

Francisco Vega, MD, PhD

The morphologic hallmark of LYG is the presence of vessel walls with a transmural infiltrate of small lymphocytes, large atypical lymphoid cells, and histiocytes with angiodestruction image.

Case of LYG with numerous EBV(+) cells as shown by in situ hybridization for EBV-encoded RNA. The number of EBV(+) cells correlates with prognosis. This case was LYG grade 3.



  • Lymphomatoid granulomatosis (LYG)


  • Angiocentric lymphoma


  • Extranodal angiocentric &/or angiodestructive B-cell lymphoproliferative disorder composed of numerous T cells and a variable number of neoplastic EBV(+) B cells


Infectious Agents

  • LYG presumably arises from EBV-immortalized B cells that have escaped immune surveillance

  • Relationship between LYG and post-transplant lymphoproliferative disorders is unclear

Clinical Associations

  • Congenital and acquired immunodeficiencies

    • Wiskott-Aldrich syndrome

    • HIV infection

    • High-dose chemotherapy



  • Incidence

    • Rare

  • Age

    • Wide age range

    • Most frequent in young adults (˜ 30-40 years)

  • Gender

    • M:F ratio = > 2:1

  • Ethnicity

    • No clear ethnic susceptibility; more common in Western countries


  • Generalized symptoms that suggest infection

  • Lung is most frequent site of involvement

    • Multiple bilateral pulmonary nodules (most frequent)

      • Lower lobes involved most often

      • Cavitation in large nodules; ˜ 25% of cases

    • Rare forms of lung involvement

      • Interstitial &/or reticulonodular patterns

      • Single &/or unilateral nodules

    • Lesions can disappear or migrate spontaneously (“wax and wane”)

  • Other sites of involvement

    • Skin (˜ 40-50%); particularly lower extremities

    • Central nervous system (˜ 30%)

    • Kidney (˜ 30%) and liver (˜ 30%)

    • Upper aerodigestive and gastrointestinal tracts uncommonly involved

    • Lymph nodes and spleen are involved rarely

Laboratory Tests

  • Peripheral blood

    • High levels of EBV DNA


  • Interferon-α 2b is reported to be effective for LYG with few EBV(+) large cells (low-grade)

  • Aggressive chemotherapy plus rituximab for LYG with numerous EBV(+) large cells


  • Number of large EBV(+) B cells correlates with prognosis

    • Also influences choice of therapy

  • Most patients have progressive course

    • Median survival: 14 months

  • Up to ˜ 25% of patients may have spontaneous remission(s)


Histologic Features

  • Angiocentric & angiodestructive lymphohistiocytic infiltrate

    • Invasion of blood vessel walls

      • Lymphocytic “vasculitis” with transmural invasion

  • Small lymphocytes admixed with histiocytes, plasma cells, and variable numbers of large atypical lymphoid cells

    • Granulocytes are rare or absent

  • Variable areas of necrosis

    • Vascular occlusion

    • Fibrinoid necrosis of blood vessels mediated by chemokines

  • Granulomas or multinucleated giant cells are not usually seen

    • Except in skin

  • Grading is based on number of EBV(+) large B cells and extent of necrosis

    • Grade 1 and 2 are considered B-cell lymphoproliferative disorder of uncertain malignant potential

      • Some cases may regress spontaneously or respond to interferon-α 2b therapy

    • Grade 3 is equivalent to diffuse large B-cell lymphoma (DLBCL)

Cytologic Features

  • Larger atypical cells have round to oval nuclei and prominent nucleoli

  • Binucleated cells are commonly seen



  • Positive for common pan-B-cell markers

    • CD19, CD20, CD22, CD79a, pax-5

  • CD45/LCA(+), CD30(+/−)

  • EBV-LMP1(+/−), CD15(−)

  • Rarely can show cytoplasmic monotypic Ig light chain in large B cells

  • Smaller reactive cells are T cells: CD3(+), CD4 > CD8

In Situ Hybridization

  • Large B cells are EBER(+)

Molecular Genetics

  • Monoclonal IgH gene rearrangements in grade 2 and 3 cases of LYG


Fungal or Mycobacterial Infections

  • Pulmonary histoplasmosis

    • Acute form

      • Flu symptoms, pulmonary infiltrates, and serologic evidence of Histoplasma infection

      • Lymphohistiocytic infiltrate with parenchymal necrosis and vasculitis (differential diagnosis with LYG grade 1)

      • Small necrotizing granulomas; granulocytes(+)

      • GMS(+), EBER(−)

    • Chronic form and histoplasmoma

      • Well-formed necrotizing granulomas; granulocytes(+)

  • Tuberculosis

    • Granulomatous inflammation with caseating necrosis; variable number of Langhans giant cells

    • M. tuberculosis organisms can be found in areas of necrosis

      • Acid-fast by Ziehl-Neelsen stain

  • Atypical mycobacteriosis

    • Immunocompromised patients &/or preexisting lung disease

    • Granulomatous inflammation with caseating necrosis; variable number of Langhans giant cells

    • Culture is required for diagnosis

Necrotizing Sarcoidosis

  • Adult females; frequently asymptomatic

  • Unilateral or bilateral lung lesions

  • Histologic features

    • Vascular granulomas surrounding, infiltrating, and destroying pulmonary arteries and veins; necrosis(+)

Wegener Granulomatosis

  • Systemic necrotizing vasculitis that primarily involves upper and lower respiratory tracts and kidneys

  • Clinical criteria

    • Nasal or oral inflammation

    • Pulmonary nodules, infiltrates, or cavities

    • Abnormal urinary sediment (usually microscopic hematuria)

    • Necrotizing granulomatous inflammation involving small arteries (by biopsy)

  • Limited Wegener granulomatosis

    • Female predominance; disease confined to lungs

  • Hallmark histologic features

    • Liquefactive &/or coagulative necrosis, geographic-shaped

    • Eosinophils(+); multinucleated giant cells without forming well-defined granulomas

    • Destructive, leukocytolytic angiitis involving arteries and veins

Diffuse Large B-cell Lymphoma

  • Primary DLBCL of lung represents < 1% of all lung neoplasms

  • Histologic features

    • Sheets of large neoplastic cells (centroblasts &/or immunoblasts)

    • ± areas of coagulative necrosis

    • Invasion of normal pulmonary structures, such as bronchial wall and pleura, is common

  • Immunophenotype

    • B-cell antigens(+), CD10(+/−), Bcl-6(+/−), EBV(−)

  • DLBCL differs from grade 3 LYG in 2 ways

    • Grade 3 LYG resembles DLBCL but usually maintains some inflammatory background

    • Grade 3 LYG is EBV(+) unlike most cases of DLBCL

Primary Mediastinal Large B-cell Lymphoma (PMLBCL)

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lymphomatoid Granulomatosis
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