Breast implant-associated anaplastic large cell lymphoma

Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes

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). 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

Cancer Category / Type

• HAEM4:Mature T- and NK-cell Neoplasms

Cancer Sub-Classification / Subtype

• HAEM5:ALK-negative 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

Sites of Involvement

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

Morphologic Features

• Large, pleomorphic
• Hallmark cells

Immunophenotype

Put your text here and fill in the table (Instruction: Can include references in the table)

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

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

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

editUnassigned References

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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 fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.)

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).

editv4:Genomic Gain/Loss/LOH

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• N/A

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: 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)

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

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 and common as well either disease defining and/or clinically significant. Can include references 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.)

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.

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

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

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

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 09/3/2024, https://ccga.io/index.php/HAEM5:Breast_implant-associated_anaplastic_large_cell_lymphoma.