Lymphoma & related disorders

Mature B cell neoplasms

Large B cell lymphomas-special subtypes

Lymphomatoid granulomatosis



Topic Completed: 15 September 2021

Minor changes: 15 September 2021

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PubMed Search: lymphomatoid granulomatosis [TI]

Nicholas Joseph Dcunha, M.B.B.S., M.D.
Elanthenral Sigamani, M.B.B.S., M.D.
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Cite this page: Dcunha NJ, Sigamani E. Lymphomatoid granulomatosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomalymphomatoidgran.html. Accessed September 21st, 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 due to the predominance of T cells on pathologic examination, was initially thought to be a T cell disorder (Am J Med 1982;72:467)
    • Subsequently, lymphomatoid granulomatosis was determined to be a B cell lymphoproliferative disorder secondary to EBV, with a prominent angiocentric T cell infiltrate (Mod Pathol 1990;3:435)
  • Lymphomatoid granulomatosis has a complex relationship with the host’s underlying immune function and defective immune surveillance of EBV infected B cells, particularly a functional defect in CD8+ cytotoxic T cells, is hypothesized to lead to disease development (Blood 1996;87:4531)
  • Particular study suggests that immunologic deficits are likely preexistent and that a quantitative or qualitative defect in mainly CD8+ cytotoxic T cells may be prerequisite for disease (Cancer 1982;49:2070)
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
  • Prognostic features are difficult to determine due the rarity of the disease
Case reports
Treatment
  • In a prospective NCI study, patients with low grade lymphomatoid granulomatosis received primary therapy with IFN-α while patients with high grade lymphomatoid granulomatosis received primary therapy with DA-EPOCH-R (dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab) every 3 weeks for up to 6 cycles of therapy (Blood 2018;132:785)
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
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
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