ALCL represent about 5% of non Hodgkin lymphomas (NHL) in adults, and 15% of pediatric NHL (i.e. 20-30% of large cell lymphomas in children). ALK+ ALCL represent 50 to 60% of ALCL cases. ALK+ ALCL predominantly affect young male patients (most cases occur before the age of 40 yrs), while ALK- ALCL is found in older patients (median age around 50 yrs) of both sex.

ALK+ ALCL presents as an aggressive disease with systemic signs, and extranodal sites (bone marrow, skin, bone, soft tissues, and organs); less agressive presentation in ALK- ALCL cases (but a worse prognosis, see below).
Note: ALK+ ALCL without the t(2;5) (so called cytoplasmic only ALK cases) show clinical features similar to those of classical ALK+ ALCL. Were found in a recent series: mean age: 19 yrs, range 4 to 45 yrs; male/female ratio: 1.5, presentation with advanced disease (stage III-IV in 9 of 15 cases), systemic symptoms (11/15), and frequent involvement of extranodal sites.

3 main histopathological types are found;

the common type, characterized by large lymphoid cells with horseshoe shaped nuclei with many nucleoli, and large cytoplasm; may be ALK + or - ALCL,

the small cell type, together with the above described cells, show small and medium sized cells; almost exclusively ALK+ cases,

the lymphohistiocytic type also contains a number of reactive histiocytes, which, earlier, lead to the misdiagnosis of malignant histiocytosis; almost always ALK+ cases.
All the 3 forms contain large cells, positive for CD30 (on the cell membrane and the golgi ); they are mostly epithelial membrane antigen (EMA) positive.
most cases are T-cell cases (often cytotoxic T-cells), or may be null cases, the null cases often involving the T-cell; B-cell cases may belong to a different category; ALK+/IgA+ immunoblastic large B-cell lymphomas could exist.
Aside are primary cutaneous anaplastic large cell lymphomas, a disease with indolent clinical course, negative for ALK, lacking the t(2;5) or variant translocations, close to the benign lymphomatoid papulosis.
Note: there are cases where the differential diagnosis between Hodgkin disease (HD) -where CD30 is also strongly expressed- and ALCL is difficult (cases previously called ALCL-HD like).

ALK+ ALCL have a favourable prognosis, whichever the ALK partner is: 70% to 80% 5 yrs survival, while ALK- ALCL cases have a much poorer prognosis (5 yrs survival in only 30%-40%). ALK+ cases without NPM1 involvement.

5 partner - 3 ALKN-term amino acids from the partner gene fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein.

Anaplastic large cell lymphoma can be classified into:

1- primary systemic ALK+ ALCL,

2- primary systemic ALK- ALCL,

3- primary cutaneous ALCL (see in paragraph Pathology).
The 2 first categories are defined according to the involvement (or not) of ALK in fusion proteins with various partners (see below); ALK+ ALCL cases are sometimes called ALK lymphomas, or ALKomas.
ALK+ ALCL can be further divided into t(2;5) cases, with NPM1-ALK fusion protein which localises both in the cytoplasm and in the nucleus, and t(2;Var), involving various partners and ALK, and a cytoplasmic localization of the fusion protein; the latter are called "cytoplasm only" ALK+ ALCL.
ALCL may also arise from transformation of another lymphoma mycosis fungoides, peripheral T-cell lymphoma, ...); these ALCL are called secondary ALCL, and they bear a poor prognosis.