Anaplastic Large Cell Lymphoma (ALK+/ALK−)
Primary Author(s)*
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WHO Classification of Disease
Structure | Disease |
---|---|
Book | WHO Classification of Tumours Central Nervous System Tumours (5th ed.) |
Category | Lymphomas |
Family | Miscellaneous rare lymphomas in CNS |
Type | Anaplastic Large Cell Lymphoma (ALK+/ALK-) |
Subtype | None |
Definition / Description of Disease
Anaplastic large cell lymphoma (ALCL) is a distinctive CD30-positive peripheral T-cell lymphoma that is rare in the CNS and is separated into two distinct types: ALK-positive (ALK+ ALCL) and ALK-negative (ALK− ALCL).
Synonyms / Terminology
None
Epidemiology / Prevalence
ALK+ ALCL occurs from early childhood to young adulthood with a male preponderance.
ALK− ALCL affects adults (median age: 65 years), also with a male preponderance.
Clinical Features
Signs and Symptoms | Headache, seizures, nausea, fever, or a combination |
Laboratory Findings | EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level) |
Sites of Involvement
ALK+ ALCL occurs as single or multiple supratentorial parenchymal lesions with or without infratentorial involvement, and rarely with spinal cord involvement. Extension to involve the meninges and (rarely) the skull can occur.
ALK− ALCL occurs as single or multiple lesions, usually supratentorial
Morphologic Features
ALK+ ALCL shows a diffuse proliferation of large atypical cells with abundant cytoplasm, including hallmark cells with bean-shaped nuclei and an eosinophilic paranuclear area
The cerebrospinal fluid may be involved. The large atypical neoplastic cells may have cytoplasmic azurophilic granules
Immunophenotype
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Finding | Marker |
---|---|
Positive (universal) | CD30+, ALK+, and EMA+, may express one or more T-cell antigens |
Positive (subset) | EXAMPLE CD2 |
Negative (universal) | EXAMPLE CD3 |
Negative (subset) | EXAMPLE CD4 |
Chromosomal Rearrangements (Gene Fusions) ALK+ ALCL
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Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
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t(2;5)(p23;q35) | NPM1::ALK fusion | 5' NPM1::3' ALK on der(5). constitutive activation of the catalytic domain of ALK. Kinase function activated by oligomerization of NPM1::ALK mediated by the NPM1 portion | EXAMPLE 30 to 50% of ALCL
(COSMIC) (add reference) |
Yes | Yes | Yes | EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|
t(X;2)(q11;p23) | 5'MSN:: 3'ALK | very rare, one case reported | For the t(X;2) translocation, localization is restricted to the membrane. | ||||
t(1;2)(q25;p23) | 5'TPM3::3'ALK | rare, four cases reported | TPM3::ALK is constitutively activated | ||||
inv(2)(p23q35) | 5'ATIC::3'ALK | rare | ider(2)(q10)inv(2) has been found in some cases, carrying 2 additional copies of the ATIC::ALK hybrid gene; frequent complex karyotypes | ||||
t(2;3)(p23;q21) | 5'TFG::3-ALK | very rare, two cases reported | |||||
t(2;17)(p23;q23) | 5'CLTC::3'ALK | very rare, one case reported | |||||
t(2;19)(p23; p13.1) | 5'TPM4::3'ALK | very rare, one case reported | |||||
t(2;22)(p23;q11.2) | 5'CLTCL1::3'ALK | very rare, one or two cases | the localization is restricted to granules (vesicles) in the cytoplasm |
Individual Region Genomic Gain/Loss/LOH
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Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
---|---|---|---|---|---|---|---|
EXAMPLE
7 |
EXAMPLE Loss | EXAMPLE
chr7:1- 159,335,973 [hg38] |
EXAMPLE
chr7 |
Yes | Yes | No | EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
EXAMPLE
8 |
EXAMPLE Gain | EXAMPLE
chr8:1-145,138,636 [hg38] |
EXAMPLE
chr8 |
No | No | No | EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference). |
Characteristic Chromosomal Patterns
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Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
---|---|---|---|---|
Complex Karyotype | ||||
+7 found in 20% of cases | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | |||
+9 in 5 to 10% of cases. | ||||
+X in 5 to 10% of cases. |
Gene Mutations (SNV/INDEL)
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Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
---|---|---|---|---|---|---|---|---|
EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference). |
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
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Genes and Main Pathways Involved
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Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
---|---|---|
EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
FISH w/ ALK BA probe
Familial Forms
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Additional Information
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Links
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References
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EXAMPLE Book
- Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
Notes
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