Breast malignant
Other malignancies
Breast implant associated anaplastic large cell lymphoma


Topic Completed: 6 January 2020

Minor changes: 6 January 2020

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Breast implant associated anaplastic large cell lymphoma[TI] pathology

Engy Abdellatif, M.B.B.Ch., M.D., Ph.D.
Dia Kamel, M.D., Ph.D.
Page views in 2019: 1,186
Page views in 2020 to date: 1,581
Cite this page: Abdellatif E, Kamel D. Breast implant associated anaplastic large cell lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantimplantalcl.html. Accessed May 29th, 2020.
Definition / general
Essential features
  • Strongly positive CD30 pleomorphic lymphocytes in the peri-implant seroma or capsular tissue
Terminology
  • Breast implant associated anaplastic large cell lymphoma is recognized as BIA-ALCL
  • Synonymous to seroma associated anaplastic large cell lymphoma
ICD coding
  • ICD-O: 9715 / 3 - mucosal associated lymphoid tissue lymphoma (MALT)
Epidemiology
Sites
  • Peri-implant seroma or capsular tissue (Ann Oncol 2016;27:306)
  • Locoregional lymph nodes may be involved
Pathophysiology
  • Although breast implants are associated with an increased risk of developing BIA-ALCL, the pathogenesis is still unknown
  • Almost all documented BIA-ALCL cases have been associated with a textured device
  • Genetic susceptibility may play a role
  • BIA-ALCL is characterized by a triple negative genetic subtype and activation of the JAK-STAT3 pathway (Aesthet Surg J 2019;39:S14)
  • Other contributing factors may include:
Etiology
  • Theoretically can be caused by active components in manufactured silicone, such as residual vinyl groups
  • Possibly a result of chronic antigenic stimulation (Aesthet Surg J 2016;36:773)
  • It is hypothesized that manufactured silicone contains several components that are potentially biologically active, such as residual vinyl groups, which can access the circulation via lymphatics leading to a foreign body carcinogenesis (Plast Reconstr Surg 2007;120:94S)
  • Another hypothesis is that breast implant associated anaplastic large cell lymphoma results from chronic bacterial antigen stimulation, sustained T cell proliferation and subsequent genetic events in the capsular tissues and the surrounding seromas (Aesthet Surg J 2016;36:773)
Diagrams / tables

Images hosted on other servers:

Anaplastic large cell
lymphoma cells in
seroma and within
fibrous capsule

Clinical features
Diagnosis
  • Pleomorphic, neoplastic, strongly positive CD30 lymphocytes present on cytology, lining the breast capsule may show capsular invasion
Laboratory
  • Not applicable
Radiology description
  • Ultrasonography can show a fluid collection between the breast implant and the capsule
  • MRI can show effusions, masses or capsular enhancement with ruptured implants
  • T2 weighted axial MRI can show a peri-implant collection around the subpectoral saline implant (Breast J 2019;25:69)
  • PET / CT: fluorodeoxyglucose (18F) avidity on positron emission tomography
Radiology images

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T1 and T2 MRI

Prognostic factors
  • 2 pathological subtypes, associated with 2 clinical pictures:
    • Effusion around the implant corresponding to a localized disease confined to the capsule
    • Palpable mass massively invading the capsule and adjacent tissues corresponding to an invasive disease
  • Generally considered an indolent T cell lymphoma but the mass forming variant requires more intensive therapeutic approaches (Ann Oncol 2016;27:306)
  • Median survival rate is 12 years
  • Those associated with tumor cells forming solid masses have adverse prognosis
Case reports
Treatment
  • In localized disease, complete capsulectomy without chemotherapy is curative
  • Adjuvant chemotherapy may be required for more invasive disease
  • Brentuximab may be used as second line treatment (Eur J Surg Oncol 2017;43:1393)
Clinical images

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Clinical presentation / intraoperative appearance

Gross description
  • Arises in the fibrous capsule rather than the breast parenchyma or skin (JPRAS O 2015;6:1)
  • Usually has fluid around the implant
Gross images

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Breast capsule

Frozen section description
  • Not applicable
Frozen section images
  • Not applicable
Microscopic (histologic) description
  • Neoplastic cells line the fibrous capsule
  • Neoplastic lymphoid cells have large malignant anaplastic nuclei, coarse and occasionally fine granular to pale chromatin with prominent nucleoli (Arch Pathol Lab Med 2014;138:842)
  • Tumor cells show eccentric, horseshoe or kidney shaped nuclei referred to as hallmark cells
  • Mitotic figures are conspicuous
  • Cells have abundant cytoplasm
  • Rarely, the malignant cells form a distinct tumor mass (Breast J 2019;25:69)
  • Malignant cells are seen in a background containing fibrinoid material and inflammatory cells
  • When forming a solid mass,
    • Can show multinodular appearance
    • Neoplastic cells are arranged in sheets
    • Can show extensive sclerosis and fibrosis
    • Can show areas of extensive coagulative necrosis
Microscopic (histologic) images

Contributed by Dia Kamel, M.D., Ph.D.

Breast capsule

Pleomorphic cells

CD30

EMA

ALK1


CD4

Cytology description
Cytology images

Contributed by Dia Kamel, M.D., Ph.D.

Cell block

Positive stains
Negative stains
  • Negative for anaplastic lymphoma kinase 1 (ALK1)
  • Frequent loss of T cell markers
Flow cytometry description
  • Identification of CD30+ atypical, large cells in peri-implant effusions with relatively increased CD40 expression may help in confirming histological diagnosis (Cytometry B Clin Cytom 2015;88:58)
Flow cytometry images

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Systemic anaplastic large cell lymphoma, ALK+

2 cases of breast
implant associated
anaplastic large
cell lymphoma

Classical Hodgkin
lymphoma compared
with anaplastic
large cell lymphoma

Molecular / cytogenetics description
  • Molecular abnormalities are similar to those seen in ALK- systemic anaplastic large cell lymphoma
  • Genomic characterization shows JAK / STAT activation and MYC / TP53 dysregulation
  • Majority of cases show clonal rearrangement of the TR genes
  • Despite molecular similarities, the clinical behavior is different as systemic anaplastic large cell lymphoma has aggressive behavior in comparison to breast implant associated anaplastic large cell lymphoma (Plast Reconstr Surg 2019;143:59S, Aesthet Surg J 2019;39:S14)
Molecular / cytogenetics images

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2D: PCR studies

Cytogenetic studies

Videos

Update on plastic surgery of anaplastic large cell lymphoma

Sample pathology report
  • Clinical details: Suspected breast implant associated anaplastic large cell lymphoma
  • Specimen: Right and left breast capsules
  • Macroscopy:
    • Right breast capsule: Capsule weighs 38 g and measures 120 x 39 x 5
    • Left breast capsule: Capsule weighs 35 g and measures 110 x 40 x 5
  • Microscopy:
    • Right breast capsule:
      • Sections of the capsule show hyalinized tissue with focal chronic inflammatory cell infiltrate and foreign body giant cell reaction to the implant material. There are occasional atypical cells of hallmark type, seen within the inner capsule surface and in one focus; the atypical lymphoid cells appear to superficially infiltrate the fibrous capsule. Immunohistochemical stains highlight the atypical lymphoid cells which show positive immunoreactivity to CD3, CD43 and CD30. On the other hand, ALK1 is negative. CD20 decorates the reactive B lymphocytes and CD68 stains macrophages.
      • The features together with the immunohistochemical staining profile are in keeping with anaplastic large cell lymphoma that is breast implant associated and involving the right breast capsule. As the atypical lymphoid cells are seen in the inner surface of the capsule, this is compatible with the effusion variant which carries a better prognosis. However, clinical and pathological correlation and followup are recommended.
    • Left breast capsule:
      • Sections show hyalinized fibrous tissue with focal chronic inflammation and foreign body giant reaction to implant material. There is no evidence of infiltration by atypical lymphoid cells in the examined sections. This is confirmed by negative immunohistochemical staining for CD30.
  • Diagnosis:
    • Right breast capsule: Breast implant associated anaplastic large cell lymphoma
    • Left breast capsule: Chronic inflammation
  • Comment: On verbal communication with the consultant radiologist, it was stated that the implant capsule is not significantly thickened and therefore this is most likely of effusion variant type.
Differential diagnosis
Board review style question #1
The hallmark cell of breast implant associated anaplastic large cell lymphoma stains strongly positive for



  1. CD20
  2. CD23
  3. CD30
  4. CD68
  5. S100
Board review style question #2
The management of patients with early / localized breast implant associated anaplastic large cell lymphoma is by

  1. Capsulectomy only
  2. Capsulectomy with radiotherapy and chemotherapy
  3. Chemotherapy only
  4. Radiotherapy and chemotherapy
  5. Radiotherapy only
Board review answer #2
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