Difference between revisions of "Anaplastic Large Cell Lymphoma (ALK+/ALK−)"

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|None
 
|None
 
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==Cancer Sub-Classification / Subtype==
 
−
Put your text here
 
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
−
Put your text here
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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==
 
==Synonyms / Terminology==
−
Put your text here
+
None
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
−
Put your text here
+
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==
 
==Clinical Features==
−
Put your text here and fill in the table
 
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
−
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
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|Headache, seizures, nausea, fever, or a combination
−
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
−
 
 
−
EXAMPLE Fatigue
 
−
 
 
−
EXAMPLE Lymphadenopathy (uncommon)
 
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
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|}
 
|}
 
==Sites of Involvement==
 
==Sites of Involvement==
−
Put your text here
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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==
 
==Morphologic Features==
−
Put your text here
+
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==
 
==Immunophenotype==
 
Put your text here and fill in the table
 
Put your text here and fill in the table
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||EXAMPLE CD1
+
|Positive (universal)||CD30+, ALK+, and EMA+, may express one or more T-cell antigens
 
|-
 
|-
 
|Positive (subset)||EXAMPLE CD2
 
|Positive (subset)||EXAMPLE CD2
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|Negative (subset)||EXAMPLE CD4
 
|Negative (subset)||EXAMPLE CD4
 
|}
 
|}
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==Chromosomal Rearrangements (Gene Fusions)==
+
==Chromosomal Rearrangements (Gene Fusions) ALK+ ALCL ==
 
Put your text here and fill in the table
 
Put your text here and fill in the table
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|t(2;5)(p23;q35) ||''NPM1''::''ALK'' fusion
−
EXAMPLE 30% (add reference)
+
|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
−
|No
 
 
|Yes
 
|Yes
 
|EXAMPLE
 
|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).
 
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).
 +
 +
 +
Localized in both cytoplasm and nucleus.
 +
 +
 +
In translocations other than the t(2;5), i.e. in t(2;Var) involving various partners and ALK, the fusion protein has a cytoplasmic localization; they are therefore called "cytoplasm only" ALK+ ALCL.
 +
|-
 +
|t(X;2)(q11;p23)
 +
|
 +
|5'MSN:: 3'ALK
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|very rare, one case reported
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|
 +
|
 +
|
 +
|For the t(X;2) translocation, localization is restricted to the membrane.
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|-
 +
|t(1;2)(q25;p23)
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|
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|5'TPM3::3'ALK
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|rare, four cases reported
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|
 +
|
 +
|
 +
|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)
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|-
 +
|t(2;19)(p23; p13.1)
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|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|-
 +
|t(2;22)(p23;q11.2)
 +
|
 +
|5'CLTCL1::3'ALK
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|very rare, one or two cases
 +
|
 +
|
 +
|
 +
|the localization is restricted to granules (vesicles) in the cytoplasm
 
|}
 
|}
 
==Individual Region Genomic Gain/Loss/LOH==
 
==Individual Region Genomic Gain/Loss/LOH==
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
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|Complex Karyotype
−
Co-deletion of 1p and 18q
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|
−
|Yes
+
|
−
|No
+
|
−
|No
+
|
 +
|-
 +
| +7 found in 20% of cases
 +
|
 +
|
 +
|
 
|EXAMPLE:
 
|EXAMPLE:
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 +
|-
 +
|<nowiki>+9 in 5 to 10% of cases.</nowiki>
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|
 +
|
 +
|
 +
|
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|-
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|<nowiki>+X in 5 to 10% of cases.</nowiki>
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|
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|
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|
 
|}
 
|}
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
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|}
 
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==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
−
Put your text here
+
FISH w/ ALK BA probe
 
==Familial Forms==
 
==Familial Forms==
 
Put your text here
 
Put your text here

Revision as of 13:50, 6 January 2024

Primary Author(s)*

Put your text here

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

Put your text here and fill in the table

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

Put your text here and fill in the table

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
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).


Localized in both cytoplasm and nucleus.


In translocations other than the t(2;5), i.e. in t(2;Var) involving various partners and ALK, the fusion protein has a cytoplasmic localization; they are therefore called "cytoplasm only" ALK+ ALCL.

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)
t(2;19)(p23; p13.1)
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

Put your text here and fill in the table

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

Put your text here

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)

Put your text here and fill in the table

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

Put your text here

Genes and Main Pathways Involved

Put your text here and fill in the table

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

Put your text here

Additional Information

Put your text here

Links

Put your text placeholder here (use "Link" icon at top of page)

References

(use "Cite" icon at top of page)

EXAMPLE Book

  1. 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

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

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