Lymphoma - Non B cell neoplasms - Anaplastic large cell lymphoma, ALK negative

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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Anaplastic large cell lymphoma, ALK negative

Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 29 September 2011, last major update September 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● ALK negative anaplastic large cell lymphoma (ALCL, ALK-) is included as a provisional entity, and is defined as a CD30+ T cell neoplasm that is not reproducibly distinguishable on morphologic grounds from ALK+ ALCL, but lacks ALK protein (WHO 2008)

Terminology
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● Previously included in the broader category of anaplastic large cell lymphoma

Epidemiology
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● Most frequently 40-65 years old
● Male predominance (M:F ratio 1.5:1)
● Most epidemiologic studies do not separate ALK+ from ALK- neoplasms

Sites
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● Frequent involvement of both lymph nodes and extranodal sites
● Usually nodal; extranodal involvement in skin, bone, soft tissue, GI tract

Etiology
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● Uncertain, some suggest it may be the final stage of histologic progression for a number of T cell lymphomas

Clinical features
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● Presentation with advanced stage III-IV disease in most patients
● Peripheral and/or abdominal lymphadenopathy, B symptoms, high International Prognostic Index

Case reports
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● Primary pulmonary (Leuk Res 2010;34:475)

Treatment and prognosis
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● Significantly worse prognosis than ALCL, ALK+ with conventional therapy (Histopathology 2003;43:462 , J Pathol 2003;200:4)
● Better prognosis than peripheral T cell lymphoma NOS (ALCL ALK- vs. PTCL: 36% vs. 20%; overall survival: 49% vs. 32%, Blood 2008;111:5496)

Postulated normal counterpart
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● Activated mature cytotoxic T cell

Micro description
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● Generally effaced architecture by solid, cohesive sheets of neoplastic cells
● Intrasinusoidal infiltrate or within T cell areas if architecture is partially preserved (mimics metastatic carcinoma)
● Large pleomorphic cells, occasional prominent nucleoli, may have multinucleated, wreath-like and “hallmark” cells, higher N/C ratio than ALCL, ALK+
● May have sclerosis and eosinophilia
● Similar morphologic variants compared to ALCL, ALK+, except for small cell

Cytology description
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● Deeply basophilic cytoplasm, prominent vacuoles, round or lobate nuclei, prominent nucleoli, clumped chromatin, multinucleation

Positive stains
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● Strong and diffuse uniform CD30 staining in all tumor cells (membrane and Golgi zone pattern, also cytoplasmic)
● Variable expression / loss of pan-T-cell antigens: CD2+ and CD3+ more often than CD5+
● Almost always CD43+
● Often CD4+, rarely CD8+
● TIA1, granzyme B, perforin, clusterin, fascin, rarely EMA

Negative stains
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● ALK, CD15, CD20, CD79a, cytokeratin, BCL2, PAX5/BSAP, PGM1, EBV (EBER & LMP1)

Genetics and Molecular
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● T-cell receptor (TCR) gene rearrangement in most cases, irrespective of T cell antigen expression
● No recurrent cytogenetic abnormality

Differential diagnosis
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● ALK positive ALCL: ALK+, younger age, less aggressive
● Primary cutaneous ALCL: much better prognosis, clinical correlation with staging necessary
● Classical Hodgkin lymphoma
● Peripheral T cell lymphoma, NOS: difficult differential, WHO recommends conservative approach (diagnose ALCL, ALK- only if very similar to ALCL, ALK+, except for ALK expression)

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Anaplastic large cell lymphoma, ALK negative

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