Table 3.

Differential Diagnosis of AITL

Entity	Confusing Features	Features Favoring Diagnosis of Entity	Features Favoring Diagnosis of AITL
Reactive paracortical hyperplasia	Paracortical expansion Immunoblastic proliferation Extrafollicular T cells with variable and weak PD1 positivity Increased vascularity	No definite cytologic atypia Strong CD10 or PD1-positive cells are confined to the germinal centers No FDC meshwork outside germinal centers No clonal rearrangement	Atypical clear cells at the outer rim of the germinal centers or around HEVs
			TFH markers such as CD10 and PD1 are strongly expressed on interfollicular or perifollicular atypical T cells
			FDC meshwork outside germinal centers
			EBV-positive immunoblasts and HRS-like cells
			Oligoclonal or monoclonal TCR rearrangement
			Monoclonal IG rearrangement sometimes present
Classic Hodgkin lymphoma	HRS-like cells, frequently EBV positive	Bands of fibrosis	Open peripheral sinuses; prominent arborizing HEVs
		Nodular growth pattern
	Polymorphic background	No atypical T-cell population	TFH markers highlight aggregates of atypical T cells surrounding the HRS-like cells The neoplastic T cells may express variable CD30 Monoclonal TCR rearrangement
		TFH markers highlight a single layer of reactive T cells forming rosettes around HRS cells
		CD30 staining restricted to the HRS cells
		No clonal TCR rearrangement
Peripheral T-cell lymphoma, NOS	Atypical T-cell population with frequent loss of T-cell antigens	Lack of characteristic TFH phenotype	Polymorphous infiltrate; Extrafollicular FDC meshwork Prominent arborizing HEVs
		Lack of extrafollicular FDC meshwork or prominent arborizing HEVs
			Expression of at least two (ideally three) TFH markers
			Occasional EBV-positive immunoblasts
Diffuse large B-cell lymphoma	Large B-cell proliferation Monoclonal IG rearrangement	Cohesive sheets of large B cells No atypical T-cell population in the background No clonal TCR rearrangement	Atypical T cells with TFH phenotype in the background
			Extrafollicular FDC meshwork
			Prominent arborizing HEVs
			Monoclonal TCR rearrangement
Nodal marginal zone lymphoma	B-cell proliferation Monoclonal plasma cells may be present	No atypical T-cell population in the background	Atypical T cells with TFH phenotype in the background
		No clonal TCR rearrangement	Extrafollicular FDC meshwork
	Extrafollicular T cells with variable and weak PD1 positivity		Monoclonal TCR rearrangement EBV-positive immunoblasts and HRS-like cells
	Monoclonal IG rearrangement

AITL, angioimmunoblastic T-cell lymphoma; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; HEV, high endothelial venules; HRS, Hodgkin/Reed-Sternberg; IG, immunoglobulin; NOS, not otherwise specified; TCR, T-cell receptor; TFH, T follicular helper.