Primary Systemic Anaplastic Large Cell Lymphoma

Differential Diagnosis

Primary Systemic Anaplastic Large Cell Lymphoma	Carcinoma
Usually CD45+ and/or CD45RO+	CD45 and CD45RO negative
ALK positive 60-85%	ALK negative
Usually T cell antigen positive	T cell antigen negative

ALCL may be EMA and infrequently keratin positive (mostly older reports)

Primary Systemic Anaplastic Large Cell Lymphoma	Anaplastic Variant Large B Cell Lymphoma	ALK Positive Large B Cell Lymphoma
Marked anaplasia	Marked anaplasia	Monomorphic with round nuclei
Frequently sinusoidal	Frequently sinusoidal	Frequently sinusoidal
CD30 >90%	CD30 variable	CD30 negative
EMA 60%	EMA 33%	EMA positive
T lineage	B lineage	B lineage
ALK immunohistology 60-85% positive	ALK immunohistology negative	ALK immunohistology 100% positive
Majority of ALK positive cases show ALK translocation such as t(2;5) or t(1:2)	Lack ALK translocation	Rare cases reported with clathrin-ALK t(2:17) gene rearrangement

ALCL may lack T markers and require genetic analysis to determine lineage

Primary Systemic ALCL	Classical Hodgkin Lymphoma
PAX5 negative	Usually PAX5 positive
Rarely CD15 positive	Usually CD15 positive
Usually clusterin positive	Rarely clusterin positive
Usually positive for T cell antigens	Rarely positive for T cell antigens
Usually T cell receptor gene rearrangement positive	Usually T cell receptor gene rearrangement negative
Hallmark cells usually present	Reed Sternberg cells usually present
Lacks conspicuously large nucleoli	Very large nucleoli

Both share anaplastic cytology, T lineage and CD30 reactivity

Primary Systemic ALCL	Primary Cutaneous ALCL
Most under age 30	Adult, rare in children
Primary nodal involvement	Primary cutaneous involvement
ALK+ 60-85% of cases	ALK negative to rare
EMA+ 60% of cases	EMA negative to rare
Majority of ALK positive cases show ALK translocation such as t(2;5) or t(1;2)	Usually negative for t(2;5) and t(1;2)

Secondary nodal involvement may be seen in primary cutaneous cases in the presence of widespread cutaneous disease