Lymphoma & related disorders
Mature B cell neoplasms
Large B cell lymphomas-special subtypes
Lymphomatoid granulomatosis


Minor changes: 15 April 2021

Copyright: 2001-2021, PathologyOutlines.com, Inc.

PubMed Search: lymphomatoid granulomatosis [TI]

Nicholas Joseph Dcunha, M.B.B.S., M.D.
Elanthenral Sigamani, M.B.B.S., M.D.
Page views in 2020: 3,712
Page views in 2021 to date: 1,498
Cite this page: Dcunha NJ, Sigamani E. Lymphomatoid granulomatosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomalymphomatoidgran.html. Accessed April 19th, 2021.
Definition / general
  • Lymphomatoid granulomatosis is an angiocentric and angiodestructive lymphoproliferative disease involving extranodal sites composed of Epstein–Barr virus (EBV) positive B cell admixed with reactive T cells, which usually predominate (Blood 2016;127:2375)
Essential features
  • Angiocentric and angiodestructive lymphoproliferative disease involving extranodal sites composed of EBV positive B cell admixed with reactive T cells
Terminology
  • Angiocentric immunoproliferative lesion
ICD coding
  • ICD-O: 9766/1 - lymphomatoid granulomatosis
  • ICD-O: 9766/3 - lymphomatoid granulomatosis, grade 3
Epidemiology
Sites
Pathophysiology
  • Lymphomatoid granulomatosis exhibits many similarities both clinically and pathologically to angiocentric T / NK cell lymphoma
    • Until recently, considered part of the same disease spectrum
  • Recent data indicates that lymphomatoid granulomatosis is an EBV positive B cell proliferation associated with an exuberant T cell reaction
    • Using variable diversity joining (VDJ) PCR, approximately 60% of cases contain clonal rearrangements
    • EBV sequences can be localized to B cells and are clonal in most cases (Cancer Surv 1997;30:233)
  • Pattern of necrosis in both lymphomatoid granulomatosis and T / NK cell lymphoma is very similar, emphasizing the probable importance of EBV in mediating the vascular damage
  • Recent studies implicate the chemokines IP-10 and Mig in the pathogenesis of the vascular damage (Cancer Surv 1997;30:233)
Etiology
  • Resembles an EBV driven lymphoproliferative disorder (Blood 1996;87:4531)
  • Also common in many immunodeficiency states, such as AIDS, allogenic organ transplant, Wiskott-Aldrich syndrome and X linked lymphoproliferative syndrome (Cancer Surv 1997;30:233)
  • Normal counterpart: mature B cell, transformed by EBV (Blood 2016;127:2375)
Clinical features
Diagnosis
  • Combination of light microscopy and immunohistochemical markers or in situ hybridization for EBV coded small RNA (EBER)
Radiology description
  • Chest Xray may show single or multiple nodules with poorly defined margins
  • CT scans show well defined and poorly defined nodules throughout both lungs (AJR Am J Roentgenol 2000;175:1335)
Radiology images

Contributed by Nicholas Joseph Dcunha, M.B.B.S., M.D. and Elanthenral Sigamani, M.B.B.S., M.D.

Mass in lung (CT scan)

Prognostic factors
  • Neurologic manifestations and large numbers of atypical lymphoreticular cells within the pulmonary infiltrate (Cancer 1979;43:360)
  • Unilateral chest lesions and large numbers of small lymphocytes and histiocytes within the infiltrate were associated with a better prognosis (Cancer 1979;43:360)
Case reports
Treatment
  • Conventionally treated by corticosteroids and chemotherapy
  • Recently, use of dose adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) or interferon has resulted in 5 year overall survival of 70% (Blood 1996;87:4531, Cancer J 2012;18:469)
Gross description
Microscopic (histologic) description
  • Angiocentric and angiodestructive polymorphous lymphoid infiltrate (Cancer 1979;43:360)
  • Lymphocytic vasculitis with infiltration of the vessel wall; may also show infarct like tissue necrosis or fibrinoid necrosis of vessel wall (Blood 1997;90:4099)
  • Infiltrate is predominantly composed of lymphocytes with admixed plasma cells, immunoblasts and histiocytes; background lymphocytes; may show atypia but are not overtly neoplastic
  • Lymphomatoid granulomatosis is composed of variable number of EBV positive B cells admixed with inflammatory background (Am J Surg Pathol 2010;34:e35)
  • EBV positive cells resemble immunoblasts or are multinucleated; may show atypia
  • Classic Reed-Sternberg cells are absent
  • Well formed granulomas are typically not seen in lungs and most other extranodal sites except skin where granulomatous reaction might be seen in subcutaneous tissue (Am J Surg Pathol 2001;25:1111)
  • Grading is based on the relative number of EBV positive B cells to the reactive lymphocyte background (Am J Surg Pathol 2015;39:141)
    • Grade I: EBV positive cells are < 5 per high power field; absent or rare large transformed cells on light microscopy; necrosis if present is focal
    • Grade II: EBV positive cells are 5 - 50 per high power field; few large transformed cells on light microscopy; necrosis is more commonly seen
    • Grade III: EBV positive cells are > 50 per high power field; large transformed cells are easily seen on light microscopy; large areas of necrosis are common
Microscopic (histologic) images

Contributed by Nicholas Joseph Dcunha, M.B.B.S., M.D. and Elanthenral Sigamani, M.B.B.S., M.D.

Lymphocytic vasculitis with angioinvasion (lung)

CD20 in tumor cells and CD3

CD30 and EBV LMP1 IHC


Lymphocytic vasculitis with angioinvasion (skin)

CD20 and CD30 in tumor cells; CD3 and CD4 in reactive T cells

Lymphocytic vasculitis with angioinvasion (CNS)

CD20 and EBV LMP1 in tumor cells; CD3 in reactive T cells

Positive stains
Molecular / cytogenetics description
  • Description of DNA / RNA findings based on testing via sequencing, PCR, FISH, CISH, ISH, cytogenetics, etc.
  • Most cases of grade II and III lymphomatoid granulomatosis show clonality for IG genes (Am J Surg Pathol 1994;18:753)
  • Clonality of grade I lymphomatoid granulomatosis is less consistent; some cases of lymphomatoid granulomatosis might be polyclonal (Am J Surg Pathol 2015;39:141)
  • T cell receptor (TR) genes do not show clonality (Hum Pathol 1991;22:1150)
Sample pathology report
  • Lung tissue, bronchoscopic biopsy:
    • Lymphomatoid granulomatosis, grade I, biopsies from left lung, upper and lower lobes (see comment)
    • Comment: The small reactive lymphoid cells are CD3 positive. The scattered large cells are positive for CD20 and CD79a and show faint membrane positivity for EBV LMP1. The MIB1 proliferation index is low (approximately 10 - 20%). Special stains for microorganisms (AFB TB, PASD, GMS) are negative.
    • Microscopic description: Dense interstitial and diffuse infiltrates of small lymphoid cells with round nuclei, clumped chromatin and scattered large lymphoid cells with round nuclei, visible nucleoli and moderate amounts of cytoplasm. Admixed with these are a few aggregates of histiocytes and occasional eosinophils. The lymphoid cells display angioinvasion with transmural infiltration by lymphocytes which adhere to the endothelium with focal luminal occlusion. There are extensive areas of necrosis with necrotic outlines of blood vessels. The adjacent lung tissue shows extensive type II pneumocyte hyperplasia.
Differential diagnosis
Board review style question #1
What cell is neoplastic in a case of lymphomatoid granulomatosis?

  1. B lymphocytes
  2. Histiocytes
  3. NK cells
  4. T lymphocytes
Board review style answer #1
A. B lymphocytes

Comment Here

Reference: Lymphomatoid granulomatosis
Board review style question #2

Which of these findings is essential for the diagnosis of lymphomatoid granulomatosis?

  1. Angioinvasion by tumor cells
  2. Granulomatous reaction
  3. Necrosis
  4. Reed-Sternberg-like cells
Board review style answer #2
A. Angioinvasion by tumor cells

Comment Here

Reference: Lymphomatoid granulomatosis
Back to top
Image 01 Image 02