Table 2 Main differential diagnoses

Immunodeficiency

Usually present

Mostly present

Mostly present

Absent

Local immunodeficiency from longstanding chronic inflammation in a restricted space

Absent

Mostly present (HIV-related or due to age, transplant, autoimmune diseases or iatrogenic)

HIV serology

+ (− in elderly and EBV-negative cases)

+ (90% of cases)

+ (almost always)

- (rarely +)

–

–

+ (often)

Age/Sex/Outcome

Adults, mainly males (HIV-negative pts. are older)

Unfavorable

Adults; HIV+ pts. mainly males

Unfavorable

Adults

Unfavorable

Adults

Often favorable

Adults

Unfavorable

Pts older than PEL pts.

Unfavorable

Adults (commonly)

Unfavorable

Clinical presentation

Effusion (classic PEL).

Extra-nodal sites (often) and lymph nodes in extracavitary PEL.

Multiple lymphadenopathy, splenomegaly, KS, systemic symptoms

Systemic disease (nodal and extranodal sites, spleen, BM)

Lymphadenopathy (usually isolated)

Tumor mass involving body cavities or narrow spaces

Effusion (without detectable tumor masses as classic PEL)

Extranodal sites; rarely lymph nodes

Association with MCD

rare

+

frequent

–

–

–

–

Histology

PB/IB generally in fluids

PB/IB (single or in small aggregates mostly in mantle and interfollicular zones)

PB/IB in sheets

PB/IB (single or in small clusters in GC)

IB/CB

IB/PB/anaplastic

PB/IB (diffuse pattern of growth)

CD20

- (can be + in extracavitary PEL)

+/−

+/−

–

+ (− in cases with plasmacytic morphology)

Often +

- or weakly + in a minority of cells

PAX5

- (can be + in extracavitary PEL)

–

–

–

+

Often +

- or weakly + in a minority of cells

CD79α

- (can be + in extracavitary PEL)

−/+

–

–

+ (− in cases with plasmacytic morphology)

Often +

+ in about 40% of cases

MUM1/IRF4

+

+

+

+ (often)

+ in cases with plasmacytic morphology

Often +

+

CD10

–

–

–

–

–

–

- (rarely +)

BCL6

–

–

–

–

–

–

–

BCL2

–

–

–

–

–

+

–

CD38

+

−/+

−/+

+/−

–

–

+

CD138

+

–

–

–

+ in cases with plasmacytic morphology

−/+

+

CD30

+

–

- (rarely +)

+/−

Often +

−/+

+

CD15

–

–

–

–

–

–

–

EMA

Often +

–

–

–

–

–

+

T cell markers

Occasionally + (especially in extracavitary PEL)

–

–

Occasionally +

Occasionally +

–

Occasionally +

Light chain restriction

Usually absent

+ cIgM lambda

+ cIgM lambda

+ kappa or lambda

Often +

Often +

+ (often IgG kappa or lambda)

HHV8

+

+

+

+

–

–

–

EBV (by LMP1)

LMP1-

LMP1-

LMP1-

LMP1- (EBNA2-, BZLF-1-, type I EBV latency)

LMP1+ (EBNA1+, EBNA2+, type III EBV latency)

–

LMP1 -

EBV (by EBER)

+ (− in HIV-negative elderly pts. and in transplanted pts)

–

–

+

+

–

+ in 60–75% of cases

Clonality

Monoclonal (IG genes hypermutated).

Rare MYC, BCL2, BCL6

polyclonal

Monoclonal (IgG genes unmutated)

Polyclonal or oligoclonal (rarely monoclonal)

Monoclonal (IG genes hypermutated)

Monoclonal (IG genes hypermutated)

Frequent MYC, BCL2, BCL6 rearrangements

Monoclonal