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

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==Definition / Description of Disease==
 
==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).<ref name=":0" />
+
Primary central nervous system lymphoma (PCNSL) represents approximately 4% of all primary brain tumors and 1% to 2% of non-Hodgkin lymphoma.<ref>Villano JL, Koshy M, Shaikh H, et al. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer. 2011;105:1414-1418.</ref> PCNSL is defined as a lymphoma confined to the brain, spinal cord, and/or eye. Diffuse large B-cell lymphomas make up more than 95% of PCNSL cases.<ref>Camilleri-Broët S, Martin A, Moreau A, et al. Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Am J Clin Pathol. 1998;110:607-612.</ref> 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).<ref name=":0" /><ref name=":2">ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, <nowiki>https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma</nowiki>.</ref><ref name=":3">ALK-positive anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, <nowiki>https://ccga.io/index.php/HAEM5:ALK-positive_anaplastic_large_cell_lymphoma</nowiki>.</ref>
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
 
None
 
None
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
ALK+ ALCL occurs from early childhood to young adulthood with a male preponderance.<ref name=":1">George, D.H.; Scheithauer, B.W.; Aker, F.V.; Kurtin, P.J.; Burger, P.C.; Cameselle-Teijeiro, J.; McLendon, R.E.; Parisi, J.E.; Paulus, W.; Roggendorf, W.; et al. Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: Prognostic Effect of ALK-1 Expression. Am. J. Surg. Pathol. 2003, 27, 487–493</ref>
+
ALK+ ALCL occurs from early childhood to young adulthood with a male preponderance.<ref name=":1">George, D.H.; Scheithauer, B.W.; Aker, F.V.; Kurtin, P.J.; Burger, P.C.; Cameselle-Teijeiro, J.; McLendon, R.E.; Parisi, J.E.; Paulus, W.; Roggendorf, W.; et al. Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: Prognostic Effect of ALK-1 Expression. Am. J. Surg. Pathol. 2003, 27, 487–493</ref><ref name=":3" />
  
ALK− ALCL affects adults (median age: 65 years), also with a male preponderance.
+
ALK− ALCL affects adults (median age: 65 years), also with a male preponderance.<ref name=":2" />
 
==Clinical Features==
 
==Clinical Features==
 
{| class="wikitable"
 
{| class="wikitable"
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|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
+
|None
EXAMPLE Lymphocytosis (low level)
 
 
|}
 
|}
 
==Sites of Involvement==
 
==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.<ref>Karikari, I.O.; Thomas, K.K.; Lagoo, A.; Cummings, T.J.; George, T.M. Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma in a Child. Pediatr. Neurosurg. 2007, 43, 516–521. [CrossRef] [PubMed]</ref>
+
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.<ref>Karikari, I.O.; Thomas, K.K.; Lagoo, A.; Cummings, T.J.; George, T.M. Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma in a Child. Pediatr. Neurosurg. 2007, 43, 516–521. [CrossRef] [PubMed]</ref><ref name=":0" />
  
ALK− ALCL occurs as single or multiple lesions, usually supratentorial
+
ALK− ALCL occurs as single or multiple lesions, usually supratentorial<ref name=":0" />
 
==Morphologic Features==
 
==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<ref>Jaffe ES. Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology. Modern Pathol. 2001;14:219-228.</ref>  
 
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<ref>Jaffe ES. Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology. Modern Pathol. 2001;14:219-228.</ref>  
  
The cerebrospinal fluid may be involved. The large atypical neoplastic cells may have cytoplasmic azurophilic granules
+
The cerebrospinal fluid may be involved. The large atypical neoplastic cells may have cytoplasmic azurophilic granules<ref name=":0" />
 
==Immunophenotype==
 
==Immunophenotype==
Put your text here and fill in the table<ref>Kadin ME. Primary Ki-1-positive anaplastic large-cell lymphoma: a distinct clinicopathologic entity. Ann Oncol. 1994;5:S25-S30.</ref>
+
Put your text here and fill in the table
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
|Positive (universal)||CD30+, ALK+, and EMA+, may express one or more T-cell antigens
+
|Positive (universal)||CD30+, ALK+, and EMA+, may express one or more T-cell antigens<ref>Kadin ME. Primary Ki-1-positive anaplastic large-cell lymphoma: a distinct clinicopathologic entity. Ann Oncol. 1994;5:S25-S30.</ref>
|-
 
|Positive (subset)||EXAMPLE CD2
 
|-
 
|Negative (universal)||EXAMPLE CD3
 
|-
 
|Negative (subset)||EXAMPLE CD4
 
 
|}
 
|}
 
==Chromosomal Rearrangements (Gene Fusions)  ALK+ ALCL==
 
==Chromosomal Rearrangements (Gene Fusions)  ALK+ ALCL==
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!Notes
 
!Notes
 
|-
 
|-
|Complex Karyotype
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|Complex Karyotype<ref name=":0" />
|
 
|
 
|
 
|
 
|-
 
| +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).
 
|-
 
|<nowiki>+9 in 5 to 10% of cases.</nowiki>
 
|
 
|
 
|
 
|
 
|-
 
|<nowiki>+X in 5 to 10% of cases.</nowiki>
 
|
 
 
|
 
|
 
|
 
|
 
|
 
|
 +
|See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with anapestic large cell lymphoma<ref name=":0" />.
 
|}
 
|}
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
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==References==
 
==References==
 
<references />(use "Cite" icon at top of page)
 
<references />(use "Cite" icon at top of page)
===<ref name=":1" />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==
 
==Notes==
 
<nowiki>*</nowiki>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.
 
<nowiki>*</nowiki>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.

Latest revision as of 22:04, 27 February 2024

Primary Author(s)*

Put your text here

WHO Classification of Disease[1]

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

Primary central nervous system lymphoma (PCNSL) represents approximately 4% of all primary brain tumors and 1% to 2% of non-Hodgkin lymphoma.[2] PCNSL is defined as a lymphoma confined to the brain, spinal cord, and/or eye. Diffuse large B-cell lymphomas make up more than 95% of PCNSL cases.[3] 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).[1][4][5]

Synonyms / Terminology

None

Epidemiology / Prevalence

ALK+ ALCL occurs from early childhood to young adulthood with a male preponderance.[6][5]

ALK− ALCL affects adults (median age: 65 years), also with a male preponderance.[4]

Clinical Features

Signs and Symptoms Headache, seizures, nausea, fever, or a combination
Laboratory Findings None

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.[7][1]

ALK− ALCL occurs as single or multiple lesions, usually supratentorial[1]

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[8]

The cerebrospinal fluid may be involved. The large atypical neoplastic cells may have cytoplasmic azurophilic granules[1]

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[9]

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[10][11] 30 to 50% of ALCL[1]

(COSF198) ([12])

Yes Yes Yes Localized in both cytoplasm and nucleus.[1]


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.[1]

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.[1]
t(1;2)(q25;p23) 5'TPM3::3'ALK rare, four cases reported TPM3::ALK is constitutively activated[1]
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[1]
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[1]

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[1] See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with anapestic large cell lymphoma[1].

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

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Li, W. The 5th Edition of the World Health Organization Classification of Hematolymphoid Tumors. In Leukemia; Weijie, L., Ed.; Exon Publications: Brisbane, Australia, 2022; pp. 1–21, ISBN 978-0-645-33207-0.
  2. Villano JL, Koshy M, Shaikh H, et al. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer. 2011;105:1414-1418.
  3. Camilleri-Broët S, Martin A, Moreau A, et al. Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Am J Clin Pathol. 1998;110:607-612.
  4. 4.0 4.1 ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma.
  5. 5.0 5.1 ALK-positive anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:ALK-positive_anaplastic_large_cell_lymphoma.
  6. George, D.H.; Scheithauer, B.W.; Aker, F.V.; Kurtin, P.J.; Burger, P.C.; Cameselle-Teijeiro, J.; McLendon, R.E.; Parisi, J.E.; Paulus, W.; Roggendorf, W.; et al. Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: Prognostic Effect of ALK-1 Expression. Am. J. Surg. Pathol. 2003, 27, 487–493
  7. Karikari, I.O.; Thomas, K.K.; Lagoo, A.; Cummings, T.J.; George, T.M. Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma in a Child. Pediatr. Neurosurg. 2007, 43, 516–521. [CrossRef] [PubMed]
  8. Jaffe ES. Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology. Modern Pathol. 2001;14:219-228.
  9. Kadin ME. Primary Ki-1-positive anaplastic large-cell lymphoma: a distinct clinicopathologic entity. Ann Oncol. 1994;5:S25-S30.
  10. Geetha, N.; Sreelesh, K.P.; Nair, R.; Mathews, A. Anaplastic large cell lymphoma presenting as a cerebellar mass. Hematol. Oncol. Stem Cell Ther. 2014, 7, 157–161.
  11. Benharroch D, Meguerian-Bedoyan Z, Lamant L, et al. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood. 1998;91:2076-2084.
  12. John G Tate, Sally Bamford, Harry C Jubb, Zbyslaw Sondka, David M Beare, Nidhi Bindal, Harry Boutselakis, Charlotte G Cole, Celestino Creatore, Elisabeth Dawson, Peter Fish, Bhavana Harsha, Charlie Hathaway, Steve C Jupe, Chai Yin Kok, Kate Noble, Laura Ponting, Christopher C Ramshaw, Claire E Rye, Helen E Speedy, Ray Stefancsik, Sam L Thompson, Shicai Wang, Sari Ward, Peter J Campbell, Simon A Forbes, COSMIC: the Catalogue Of Somatic Mutations In Cancer, Nucleic Acids Research, Volume 47, Issue D1, 08 January 2019, Pages D941–D947,

(use "Cite" icon at top of page)

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.