HAEM5:Breast implant-associated 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:Breast Implant-Associated Anaplastic Large Cell Lymphoma.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. 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 to a table, click within the table and select the > symbol that appears to be given options. 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)*

Derick Okwan-Duodu, MD, PhD; Sumire Kitahara, MD

Cedars-Sinai Medical Center

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)	Breast implant-associated anaplastic large cell lymphoma

Definition / Description of Disease

• Provisional entity in WHO 2016 classification
• Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T-cell lymphoproliferative disorder that occurs in patients with breast implants.
• Belongs to the so-called triple negative category of systemic anaplastic large cell lymphomas (sALCL)

Synonyms / Terminology

• Seroma-associated anaplastic large cell lymphoma

Epidemiology / Prevalence

• Rare (fewer than 1 in 100,000 with implants)
• No association with type of implant (silicone vs. saline, textured vs. smooth)
• Median time to lymphoma diagnosis after implant is 8-9 years
• Mean age 50

Clinical Features

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Signs and Symptoms	EXAMPLE: Asymptomatic (incidental finding on complete blood counts) EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE: Cytopenias EXAMPLE: Lymphocytosis (low level)

editv4:Clinical Features

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• Pain, swelling around implant
• Peri-implant effusion most common (approximately 80% cases)
• Axillary lymphadenopathy
• Extracapsular extension to form a solid mass of tumor cells possible

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Sites of Involvement

• Peri-implant (Stage I)
• Extracapsular dissemination not uncommon

Morphologic Features

• Large, pleomorphic
• Hallmark cells

Immunophenotype

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Finding	Marker
Positive (universal)	EXAMPLE: CD1
Positive (subset)	EXAMPLE: CD2
Negative (universal)	EXAMPLE: CD3
Negative (subset)	EXAMPLE: CD4

editv4:Immunophenotype

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Finding	Marker
Positive (universal)	CD30
Positive (frequent)	Varying pan T-cell antigen expression (CD3, CD2, CD5, CD7, CD4, CD8), MUM1
Negative (universal)	ALK

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Chromosomal Rearrangements (Gene Fusions)

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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
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add reference)	Yes	No	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).

editv4:Chromosomal Rearrangements (Gene Fusions)

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• Not described

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

Please incorporate this section into the relevant tables found in:

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

THIS SECTION IS REALLY FOR THE DIAGNOSTIC, PROGNOSTIC, AND THERAPEUTIC SIGNIFICANCE OF THE MOLECULAR CHANGES FOUND IN THIS ENTITY. YOU CAN KEEP THE WORK YOU HAVE DONE BUT PERHAPS MOVE IT TO "OTHER INFORMATION" SECTION?

• Diagnosis
  • Clinical history (skin rash, ulcer or skin mass > 1 year after breast implant),
  • Ultrasound or MRI
  • Fine needle aspiration or tissue biopsy for morphologic and immunophenotypic analysis
  • For disseminated disease, clinical history of breast implants and negative DUSP22 and TP63 FISH studies strongly supports diagnosis and makes other sALCL's unlikely
• Prognosis
  • Excellent prognosis (median survival over 12 years)
  • If extracapsular extension present, systemic therapy may be indicated
• Therapeutic Implications
  • Focal disease: capsulectomy and implant removal followed by radiotherapy or watchful waiting
  • Disseminated disease: systemic therapy
  • Anthracyclin-based chemotherapy with brentuximab-vedotin superior to chemotherapy alone

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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).

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• N/A

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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
EXAMPLE: Co-deletion of 1p and 18q	Yes	No	No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

editv4:Characteristic Chromosomal Aberrations / Patterns

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• N/A

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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.

editv4:Gene Mutations (SNV/INDEL)

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• JAK1 and STAT3 mutation (variable pattern leads to activation)

PUT IN THE TABLE FROM THE TEMPLATE, SO THE FREQUENCY OF THESE MUTATIONS AND THEIR SIGNIFICANCE CAN BE ENTERED.

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Epigenomic Alterations

• Not described

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

editv4:Genes and Main Pathways Involved

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• JAK/STAT activation
• MYC/TP53 dysregulation

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Genetic Diagnostic Testing Methods

• Morphologic and immunohistochemical evaluation of aspirated seroma/effusion fluid and/or capsulectomy specimen
• Exclude secondary involvement by systemic ALK(-) ALCL

Familial Forms

• None

Additional Information

• None

Links

• HAEM5:ALK-negative anaplastic large cell lymphoma
• HAEM5:ALK-positive anaplastic large cell lymphoma

References

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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. *Citation of this Page: “Breast implant-associated anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/10/2025, https://ccga.io/index.php/HAEM5:Breast_implant-associated_anaplastic_large_cell_lymphoma.