Breast
Other malignancies
Breast implant associated anaplastic large cell lymphoma
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last author update: 6 January 2020
Last staff update: 19 January 2024
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PubMed Search: Breast implant associated anaplastic large cell lymphoma pathology
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Flow cytometry description | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Abdellatif E, Kamel D. Breast implant associated anaplastic large cell lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantimplantalcl.html. Accessed April 25th, 2024.
Definition / general
- A new provisional entity recognized in the 2017 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Mod Pathol 2019;32:166)
- Arising primarily in association with breast implants
- Rare type of non-Hodgkin lymphoma characterized by abnormal growth of strongly positive CD30 lymphocytes within the breast capsule
- Features are not different from ALK- anaplastic large cell lymphoma
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
- 1:3,817 - 1:30,000 women with textured implants (Plast Reconstr Surg 2017;140:645)
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:
- Particle erosion of the implants (Breast Cancer Res Treat 2016;156:65)
- A subclinical biofilm
- Chronic T cell stimulation (Dtsch Arztebl Int 2018;115:628)
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
- On average, develops 10.9 years after the initial implants have been placed
- Unilateral effusion confined to the capsule, pain, rash, mass or ulceration of affected breast
- Can form a mass that invades locally through the capsule into breast parenchyma or soft tissue or spreads to regional lymph nodes (Mod Pathol 2019;32:166)
- Axillary lymphadenopathy may be present in up to 29% but not always positive for tumor (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
Diagnosis
- Pleomorphic, neoplastic, strongly positive CD30 lymphocytes present on cytology, lining the breast capsule may show capsular invasion
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
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
- 32 year old woman presented with several weeks of pain and firmness in right breast (Cureus 2016;8:e546)
- 33 year old transgender woman with 5 cm tumorous mass (Aesthetic Plast Surg 2018;42:451)
- 53 year old woman with Li-Fraumeni syndrome and a history of breast cancer (Case Rep Genet 2019;2019:5647940)
- 54 year old transgender African American woman was treated with radiotherapy (J Investig Med High Impact Case Rep 2019;7:2324709619842192)
- 61 year old woman with right breast fullness and fluid collection around right breast silicone implant (Case #512)
- 65 year old Caucasian woman with prior bilateral fibrocystic breast disease (Case Rep Oncol Med 2017;2017:6478467)
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
Images hosted on other servers:
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
Images hosted on other servers:
Breast capsule
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
Contributed by Andrii Puzyrenko, M.D., Ph.D. and Julie Jorns, M.D. (Case #512)
Capsule
Aspirated fluid
Cytology description
- CD30+ tumor cells can be recognized in samples aspirated from breast implants (Cytopathology 2018;29:294)
Cytology images
Contributed by Dia Kamel, M.D., Ph.D.
Cell block
Positive stains
- CD2, CD3, CD4, CD43 and CD30 (strong and uniform)
- Majority express cytotoxic markers
- Minority of cases express epithelial membrane antigen (EMA) (Breast J 2019;25:69)
- Overall similar immunophenotype to ALK- anaplastic large cell lymphoma
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)
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
Images hosted on other servers:
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.
- Right breast capsule:
- 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
- Inflammation: reactive T lymphocytes are seen and absence of large and anaplastic CD30+ cells (reactive infiltrate may have scattered nonanaplastic CD30+ immunoblasts)
- Other types of non-Hodgkin lymphoma: absence of CD30 strongly positive tumor cells
- Primary or recurrent carcinoma: cohesive architectural pattern that mimics carcinoma, which is positive for cytokeratin and negative for CD30 and T cell antigens (Arch Pathol Lab Med 2014;138:842)
- Anaplastic large cell lymphoma with EMA positivity should be differentiated from high grade triple negative breast carcinoma
- Systemic anaplastic large cell lymphoma
- CD30+ lymphomas such as classical Hodgkin lymphoma, especially when anaplastic large cell lymphoma loses T cell markers
Additional references
Board review style question #1
The hallmark cell of breast implant associated anaplastic large cell lymphoma stains strongly positive for which of the following?
- CD20
- CD23
- CD30
- CD68
- S100
Board review style answer #1
C. CD30. Breast implant associated anaplastic large cell lymphoma is characterized by abnormal growth of pleomorphic lymphocytes within the peri-implant seroma or capsular tissue. Answers A and D are incorrect because CD20 stains the reactive B lymphocytes and CD68 highlights histiocytic and monocytic cells / macrophages, which aren't the hallmark cells for this condition. Answers B and E are incorrect because CD23 and S100 are not useful for characterizing this condition.
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Board review style question #2
Which of the following is best for management of patients with early / localized breast implant associated anaplastic large cell lymphoma?
- Capsulectomy only
- Capsulectomy with radiotherapy and chemotherapy
- Chemotherapy only
- Radiotherapy and chemotherapy
- Radiotherapy only
Board review style answer #2
A. Capsulectomy only. In early, localized disease, complete casulectomy without chemotherapy is curative. Answers B - E are incorrect because in early disease, radiotherapy and chemotherapy are not needed. Adjuvant chemotherapy may be required for more invasive disease.
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