ALK-negative anaplastic large cell lymphoma

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Anaplastic Large Cell Lymphoma, ALK-Negative.

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Miguel Gonzalez Mancera, MD

Sumire Kitahara, MD

Cedars-Sinai, Los Angeles, CA

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	T-cell and NK-cell lymphoid proliferations and lymphomas
Family	Mature T-cell and NK-cell neoplasms
Type	Anaplastic large cell lymphoma
Subtype(s)	ALK-negative anaplastic large cell lymphoma

WHO Essential and Desirable Genetic Diagnostic Criteria

(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)

WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

Acceptable	Anaplastic large cell lymphoma, ALK-negative
Not Recommended	N/A

Gene Rearrangements

Driver Gene	Fusion(s) and Common Partner Genes	Molecular Pathogenesis	Typical Chromosomal Alteration(s)	Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE: ABL1	EXAMPLE: BCR::ABL1	EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.	EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: Common (CML)	EXAMPLE: D, P, T	EXAMPLE: Yes (WHO, NCCN)	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). BCR::ABL1 is generally favorable in CML (add reference).
EXAMPLE: CIC	EXAMPLE: CIC::DUX4	EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5.	EXAMPLE: t(4;19)(q25;q13)	EXAMPLE: Common (CIC-rearranged sarcoma)	EXAMPLE: D		EXAMPLE: DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
EXAMPLE: ALK	EXAMPLE: ELM4::ALK Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1	EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18.	EXAMPLE: N/A	EXAMPLE: Rare (Lung adenocarcinoma)	EXAMPLE: T		EXAMPLE: Both balanced and unbalanced forms are observed by FISH (add references).
EXAMPLE: ABL1	EXAMPLE: N/A	EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.	EXAMPLE: N/A	EXAMPLE: Recurrent (IDH-wildtype Glioblastoma)	EXAMPLE: D, P, T

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(6;7)(p25.3;q32.3)	DUSP22/FRA7H	DUSP22/FRA7H fusion protein	30%	No	Yes	No	* These rearrangements are considered mutually exclusive; however, a single case with both DUSP22 and TP63 rearrangement has been described. Can also be seen in a fraction of other PTCL. 5-year overall survival > 90% Therapeutic Implications Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site High dose chemotherapy and autologous stem cell transplantation for remission DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission Theoretical: Ruxolitinib may be used to target JAK-STAT pathway (not FDA-approved) Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway
*t(3;3)(q22;q26.2), inv(3)(q26q28)	TP63/TBL1XR1	TP63/TBL1XR1 fusion protein	8%	No	Yes	No	*See t(6;7) notes 5-year overall survival 17%
t(10;19)(q24;p13)	NFKB2/TYK2	NFKB2/TYK2 fusion protein	rare	No	No	No	5-year overall survival 42% for cases lacking all DUSP22, TP63 and ALK rearrangements
t(1;19)(p34;p13)	PABPC4/TYK2	PABPC4/TYK2 fusion protein	rare	No	No	No
t(6;10)(q22;q24)	NFKB2/ROS1	NFKB2/ROS1 fusion protein	rare	No	No	No

editv4:Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Prevalence
*t(6;7)(p25.3;q32.3)	DUSP22/FRA7H	30%
*t(3;3)(q22;q26.2), inv(3)(q26q28)	TP63/TBL1XR1	8%
t(10;19)(q24;p13)	NFKB2/TYK2	rare
t(1;19)(p34;p13)	PABPC4/TYK2	rare
t(6;10)(q22;q24)	NFKB2/ROS1	rare

* These rearrangements are considered mutually exclusive; however, a single case with both DUSP22 and TP63 rearrangement has been described. Can also be seen in a fraction of other PTCL.

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editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

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• Chromosomal Rearrangements (Gene Fusions)
• Individual Region Genomic Gain/Loss/LOH
• Characteristic Chromosomal Patterns
• Gene Mutations (SNV/INDEL)

• Diagnosis
  • In general, ALK(-) ALCL has a worse prognosis when compared to ALK (+) ALCL
  • ALK(-) ALCL has shown superior prognosis when compared to PTCL, NOS. The 5-year failure-free survival rate was 36% vs 20%, and overall survival rate was 49% vs 32%

• Prognosis
  • When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however:
    • When stratified for age, prognosis between ALK(-) and ALK(+) ALCL appears similar
  • 5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements
  • Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to TP53 deletion due to study size
    • Often concomitant loss and seen in almost a quarter of cases
  • Mutations with significantly shorter OS compared to wild-type
    • STAT3, TP53
  • Prognostic significance of ERB4 and COL29A1 co-expressing subtypes unclear

• Therapeutic Implications
  • Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site
  • High dose chemotherapy and autologous stem cell transplantation for remission
  • DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
  • Theoretical:
    • Ruxolitinib may be used to target JAK-STAT pathway (not FDA-approved)
    • Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway

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Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)

Chr #	Gain, Loss, Amp, LOH	Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]	Relevant Gene(s)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7	EXAMPLE: Unknown	EXAMPLE: D, P	EXAMPLE: 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 references).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8	EXAMPLE: Unknown	EXAMPLE: D, P		EXAMPLE: Common recurrent secondary finding for t(8;21) (add references).
EXAMPLE: 17	EXAMPLE: Amp	EXAMPLE: 17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]	EXAMPLE: ERBB2	EXAMPLE: D, P, T		EXAMPLE: Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

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
1q	Gain			No	No	No	Prevalence 30% Numerous genes affected
6p	Gain	25.3		No	No	No	Prevalence 30% Gene affected: DUSP22
8q	Gain	24.22		No	No	No	Prevalence 16-23% Genes affected: NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1
1p	Loss	13.3-p12 36.33-36.32		No	No	No	Prevalence 19-26%
6q	Loss > CN-LOH	21		No	No	No	Prevalence 35% Genes affected: PRDM1, ATG5
10p	Loss	11.23-p11.22		No	No	No	Prevalence 23%
13q	Loss	32.3-q33.3		No	No	No	Prevalence 23% Genes affected: CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1
16q	Loss	23.2		No	No	No	Prevalence 29% Genes affected: MAF, WWOX
17p	Loss	13.3-p12		No	Yes?**	No	Prevalence: 42% Gene affected: TP53

editv4:Genomic Gain/Loss/LOH

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The pattern of genomic copy number changes and loss of heterozygosity have been described:

• In general, recurrent lesions are more common in ALK(-) than ALK(+) disease
• 6q21 losses associated with 17p deletions seen in ~25% of cases of ALK(-) ALCL
• None are diagnostically helpful for the distinction between ALK(-) ALCL from other entities

Chromosome Number	Gain/Loss/Amp/LOH	Region	Genes	Prevalence
1q	Gain		numerous	30%
6p	Gain	25.3	DUSP22	30%
8q	Gain	24.22	NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1	16-23%
1p	Loss	13.3-p12 36.33-36.32		26% 19%
6q	Loss > CN-LOH; See also below for somatic mutations	21	PRDM1, ATG5	35%
10p	Loss	11.23-p11.22		23%
13q	Loss	32.3-q33.3	CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1	23%
16q	Loss	23.2	MAF, WWOX	29%
17p	Loss	13.3-p12	TP53	42%

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Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Chromosomal Pattern	Molecular Pathogenesis	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE: Co-deletion of 1p and 18q	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).	EXAMPLE: Common (Oligodendroglioma)	EXAMPLE: D, P
EXAMPLE: Microsatellite instability - hypermutated		EXAMPLE: Common (Endometrial carcinoma)	EXAMPLE: P, T

editv4:Characteristic Chromosomal Aberrations / Patterns

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• Gene expression profiling and comparative genomic hybridization studies have shown that ALK(+) and ALK(-) ALCL share restricted genomic signatures and/or preferential genomic aberrations
• Several genes are similarly expressed in ALK(+) and ALK(-) samples, suggesting a common ALCL signature, that permit differential diagnosis of ALCL from PTCL-NOS
• See other sections.

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Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Gene	Genetic Alteration	Tumor Suppressor Gene, Oncogene, Other	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE:EGFR	EXAMPLE: Exon 18-21 activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (lung cancer)	EXAMPLE: T	EXAMPLE: Yes (NCCN)	EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations	EXAMPLE: Variable LOF mutations	EXAMPLE: Tumor Supressor Gene	EXAMPLE: Common (breast cancer)	EXAMPLE: P		EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations	EXAMPLE: Activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (melanoma)	EXAMPLE: T

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

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
TP53	TSG	23%	No	N/A	No	Yes	No
STAT3	Oncogene	26%	No	N/A	No	Yes	No	Not seen in PTCL-NOS or ALK+ ALCL Ruxolitinib may be used to target JAK-STAT pathway (not FDA-approved)
JAK1	Oncogene	26%	No	N/A	No	Yes	No	Not seen in PTCL-NOS or ALK+ ALCL
PRDM1/BLIMP1	TSG	6%	No	N/A	No	No	No
NOTCH1	Oncogene	15%	No	No	No	No	No
KMT2D	TSG	20%	No	No	No	No	No

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.

editv4:Gene Mutations (SNV/INDEL)

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Gene	Presumed mechanism	Frequency	Notes
STAT3*	Activating	10-26%	Not seen in PTCL-NOS or ALK+ ALCL
JAK1*	Activating	15-26%	Not seen in PTCL-NOS or ALK+ ALCL
PRDM1/BLIMP1	Tumor suppressor	6% (2/31)
NOTCH1	Activating	15%
TP53	Tumor suppressor	23%
KMT2D	Tumor suppressor	20%

*Double mutated for JAK1+STAT3 in 7-11%

Other mutations

• Epigenetic modifier genes: TET2
• Uncommon: FAS, STIM2; LRP1B (9%), EPHA5

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Epigenomic Alterations

• See above mutations in epigenetic modifier genes

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
STAT3	JAK-STAT pathway	Increased cell growth and proliferation
NFkB2-ROS1 fusion	JAK-STAT pathway	Increased cell growth and proliferation
NFkB2-TYK2 fusion	JAK-STAT pathway	Increased cell growth and proliferation

editv4:Genes and Main Pathways Involved

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• JAK-STAT
  • STAT3 mutants are constitutively phosphorylated
  • JAK1 mutants lead to the constitutive phosphorylation of STAT and synergize with STAT3 mutants
  • When JAK/STAT3 mutations absent, NFkB2-ROS1 and NFkB2-TYK2 fusions may constitutively activate STAT pathway

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Genetic Diagnostic Testing Methods

• Morphologic and immunophenotypic characterization
  • Strong CD30 staining of equal intensity help distinguish from PTCL, NOS, classic Hodgkin lymphoma, diffuse large B-cell lymphoma, and monomorphic epitheliotropic intestinal T-cell lymphoma
  • Exclusion of ALK(+) ALCL cases by immunostain for ALK
  • P63 immunostain to identify TP63 rearranged. Immunophenotyping is not sensitive and is thus used as screening before FISH analysis. A ≥ 30% threshold yields 100% sensitivity
• Presence of STAT3 and/or JAK1 mutations seem to favor ALK(-) ALCL over PTCL-NOS
• FISH studies necessary to subtype:
  • DUSP22 (IRF4/DUSP22) break-apart probe
  • TP63 rearrangement
• ERBB4(+) cases may be identified using digital droplet PCR or immunostaining for MMP9 (a protein highly correlated with ERBB4 expression)
  • Not routinely performed

Familial Forms

• Not described

Additional Information

This disease is defined/characterized as detailed below:

Anaplastic large cell lymphomas (ALCL), ALK-negative, is a CD30+ T-cell lymphoma that is morphologically and immunophenotypically indistinguishable (but lacks ALK protein expression) from ALK(+) ALCL

• Three major molecular subtypes of ALK (-) ALCL:
  • DUSP22-rearranged subtype (30%)
  • TP63-rearranged subtype (8%)
  • Triple-negative subtype (DUSP22 negative, TP63 negative, ALK negative)
  • Emerging subtypes:
    • ERBB4 expression (~25%): mutually exclusive with other rearrangements (TP63, DUSP22, ROS or TYK translocations)

The epidemiology/prevalence of this disease is detailed below:

• More common in adults than children (peak incidence 6th decade of life)
• Less than 3% of all Non-Hodgkin's lymphoma
• M:F 1.5:1

The clinical features of this disease are detailed below:

Signs and symptoms - B-symptoms (weight loss, fever, night sweats); Peripheral and/or Lymphadenopathy; Most patients present with advanced stage disease

Laboratory findings - Not specific

The sites of involvement of this disease are detailed below:

• Nodal (predominantly abdominal lymphadenopathy) in a sinusoidal pattern
• Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases
  • If involving the skin or GI tract, cases must be distinguished from primary cutaneous ALCL or CD30+ enteropathy-associated/other intestinal T-cell lymphomas, respectively

The morphologic features of this disease are detailed below:

• Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells, with or without prominent nucleoli, with varying proportions of hallmark cells
• "Hallmark cells"
  • Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
  • Usually large in size, but may also be smaller
  • Less common that in classic variant of ALK (+) ALCL
• DUSP22-rearranged subtype tends to lack large pleomorphic cells and show smaller, monomorphic cells with central nuclear pseudoinclusions (doughnut cells)
• Intrasinusoidal growth pattern seen in cases with preserved nodal architecture

The immunophenotype of this disease is detailed below:

Immunohistochemical patterns vary by subtype

DUSP22-rearranged subtype

Finding	Marker
Positive (universal)	CD30*, CD43 (almost universally)
Negative (universal)	ALK, TP63, EBER, LMP-1
Positive (frequent)	CD2, CD3, CD4+ cases more common than CD8, CD5, Clusterin
Negative (frequent)	TIAI, granzyme B, perforin, EMA, PAX5

*Strong and diffuse CD30 staining; should be equal intensity in all cells

TP63-rearranged subtype

Finding	Marker
Positive (universal)	CD30*, CD43 (almost universally), P63, CD4+ cases more common than CD8
Negative (universal)	ALK, EBER, LMP-1
Positive (frequent)	CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, clusterin
Negative (very frequent)	EMA

Triple-negative subtype

Finding	Marker
Positive (universal)	CD30*, CD43 (almost universally), CD2, CD3, CD4+ cases more common than CD8, CD5, TIA1, granzyme B, perforin, EMA
Negative (universal)	ALK, P63, EBER, LMP-1
Positive (common)	EMA, clusterin
Negative (frequent)	PAX5, CD20, CD79a, CD15

Links

• See references.

References

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Notes

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Prior Author(s):

*Citation of this Page: “ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 05/25/2025, https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma.