Lymphomatoid Granulomatosis

Question 1

What is the definition of Lymphomatoid Granulomatosis (LyG) ?

Answer 1

• angiocentric and angiodestructive lymphoproliferative disorders
• often involve extranodal sites
• predominantly reactive T cells with admixed EBV-positive large B cells
  
  • grading and severity of the lesions is dependent on the proportion of large B cells

Question 2

What is the epidemiology of LyG ?

Answer 2

• usually presents in older adults
  
  • BUT: kids with immunodeficiency disorders can get these lesions
• M > F
• appears more common in western countries compared to Asia

Question 3

What is the etiology of LyG ?

Answer 3

• EBV driven lymphoproliferative disorder
  
  • patients with immunodeficiency are at an increased risk
• What predisposing conditions can lead to this:
  
  • allogeneic stem cell transplant
  • Wiskott-Aldrich syndrome (eczema, thrombocytopenia-immunodeficiency syndrome)
  • HIV infection
  • X-linked lymphoproliferative syndrome

Question 4

What locations are usually affected by LyG ?

Answer 4

• > 90% of patients have pulmonary involvement (usually involved at presentation)
  
  • lower respiratory tract
• other common sites of involvement
  
  • brain
  • kidneys
  • liver
  • skin
• lymph nodes and spleen are rarely involved
• upper respiratory tract and GI tract are rarely involved

Question 5

What are the clinical features often associated with LyG ?

Answer 5

• Often signs and symptoms due to respiratory tract involvement:
  
  • cough, dyspnea, and chest pain
• Constitutional symptoms
  
  • fever, malaise, weight loss, arthralgias, neurological symptoms
  • if the CNS is involved, symptoms vary based on site of involvement

IMP: very few patients present with asymptomatic disease

Question 6

What can be seen grossly ?

Answer 6

• most frequently presents with pulmonary nodules
• usually bilateral lesions
• central necrosis and cavitation can be seen in larger lesions
• skin lesions are very diverse in appearances

Question 7

What are the key microscopic findings ?

Answer 7

• angiocentric and angiodestructive polymorphous lymphoid infiltrate
• lymphocytes predominate but have background plasma cells, immunoblasts and histiocytes
• the background small lymphocytes can look irregular but not overly neoplastic
• variable, EBV positive B cells
  
  • some atypia but look like immunoblasts
  • rarely have RS like appearance but classic RS cells should not be present
• usually no well-formed granulomas in the lungs
  
  • BUT granulomatous reactions are common in the skin
• Lymphocytic vasculitis is quite prominent
  
  • fibrinoid necrosis is caused by EBV driven chemokines

Question 8

Which entity must LyG be differentiated from ?

Answer 8

• Extranodal NK/T cell lymphoma
  
  • angiodestructive
  • also associated with EBV

Question 9

What is the immunophenotype of LyG ?

Answer 9

• EBV positive B cells usually express CD20
• Variably positive for CD30
  
  • negative for CD15 (if positive think of Hodgkin lymphoma)
• Background lymphocytes
  
  • CD3+ T cells
  • CD4 > CD8

Question 10

What is the postulated normal counterpart for LyG ?

Answer 10

• A mature B cell, transformed by EBV

Question 11

How is LyG graded ?

Answer 11

• you compare the proportion of EBV+ large B cells to the small lymphocyte background
• IMP:
  
  • must differentiate grade 3 from grade 1-2
  • if no polymorphous background and sheets of large cells, classify as EBV+ DLBCL

Question 12

What is the definition of a Grade 1 lesion?

Answer 12

• polymorphous lymphoid infiltrate without cytological atypia
• large, transformed cells are absent or rare
  
  • better appreciated by IHC
• if present, necrosis is usually focal
• <5 /HPF
  
  • in some cases EBV + cells may be absent
  • BUT the diagnosis should be made with caution in these scenarios

Question 13

What is the definition of a Grade 2 lesion ?

Answer 13

• contain occasional large cells in a polymorphous background
  
  • small clusters can be seen especially when highlighted by CD20