Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease

HHV8-positive plasmablastic lymphoma (HHV8 PL)

Epidemiology and Etiology:

• HIV infection usually
• If HIV negative, usually in regions where HHV8 is endemic (Africa and Mediterranean countries)
• HHV8-associated multicentric Castleman disease (HHV8 MCD) background
• HHV8-positive neoplastic cells always

Common sites:

• Lymph nodes
• Spleen
• Other viscera
• Liver
• Lung
• GI tract
• Leukemia rarely

Gross features:

• Enlarging lymph nodes
• Massive splenomegaly

Histologic features:

• HHV8 MCD:
• Involution and hyalinization of germinal centres
• Prominent mantle zone
• may intrude into the germinal centres and completely efface them
• plasmablastic cells among mantle zone cells and scattered in the interfollicular area maybe
• variable numbers
• dense amphophilic cytoplasm
• vesicular, often eccentrically placed nuclei
• one or two prominent nucleoli
• interfollicular area heavily infiltrated by mature plasma cells
• with progression, plasmablasts coalesce to form confluent microscopic clusters (microlymphomas) and sheets within and outside germinal centres
• HHV8-positive plasmablastic lymphoma (PL):
• Expansion of the small confluent sheets of HHV8-positive plasmablasts to completely efface the lymph node and splenic architecture

Immunophenotype:

Marker:	Sensitivity:	Specificity:
cIgM
HHV8 latent nuclear antigen 1 (LANA-1) (stippled nuclear pattern)	All cases
Lambda light chain restriction
CD20	+/-
CD79a (neg)
CD138 (neg)
CD38	-/+
CD27 (neg)
EBER (neg)
cIgA (interfollicular plasma cells, typically cIgM negative, HHV8 negative, and polytypic)

Molecular features:

• Without IG somatic hypermutation
• Monoclonal
• Microlymphomas may be mono- or polyclonal
• Plasmablasts in HHV8 MCD are a polyclonal population despite monotypic IgM expresssion

Other features:

• HHV8 MCD and PL are both highly aggressive disorders with a median survival of a few months
• Profound immunodeficiency
• Kaposi sarcoma often accompanying
• Primary effusion lymphoma (PEL) and its extracavitary counterpart may complicate HHV8 MCD
• No expression of Ig
• Usually co-infected with EBV
• Germinotrophic lymphoproliferative disorder is another monotypic HHV8-positive lymphoproliferative lesion that occurs in HIV negative individuals
• Plasmablasts either kappa or lambda light chain restriction
• Polyclonal
• EBV co-infection

References: