scholarly journals Chromosome 20 loss is characteristic of breast implant–associated anaplastic large cell lymphoma

Blood ◽  
2020 ◽  
Vol 136 (25) ◽  
pp. 2927-2932
Author(s):  
G. Tjitske Los-de Vries ◽  
Mintsje de Boer ◽  
Erik van Dijk ◽  
Phylicia Stathi ◽  
Nathalie J. Hijmering ◽  
...  

Abstract Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare type of T-cell lymphoma that is uniquely caused by a single environmental stimulus. Here, we present a comprehensive genetic analysis of a relatively large series of BIA-ALCL (n = 29), for which genome-wide chromosomal copy number aberrations (CNAs) and mutational profiles for a subset (n = 7) were determined. For comparison, CNAs for anaplastic lymphoma kinase (ALK)− nodal anaplastic large cell lymphomas (ALCLs; n = 24) were obtained. CNAs were detected in 94% of BIA-ALCLs, with losses at chromosome 20q13.13 in 66% of the samples. Loss of 20q13.13 is characteristic of BIA-ALCL compared with other classes of ALCL, such as primary cutaneous ALCL and systemic type ALK+ and ALK− ALCL. Mutational patterns confirm that the interleukin-6–JAK1–STAT3 pathway is deregulated. Although this is commonly observed across various types of T-cell lymphomas, the extent of deregulation is significantly higher in BIA-ALCL, as indicated by phosphorylated STAT3 immunohistochemistry. The characteristic loss of chromosome 20 in BIA-ALCL provides further justification to recognize BIA-ALCL as a separate disease entity. Moreover, CNA analysis may serve as a parameter for future diagnostic assays for women with breast implants to distinguish seroma caused by BIA-ALCL from other causes of seroma accumulation, such as infection or trauma.

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Parisa Moori ◽  
Fran Ibison ◽  
Deepa Jacob ◽  
Julie Iddon

Abstract Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, non-Hodgkin lymphoma which arises within the capsules of breast implants. These particular tumours have expression of CD30 and are negative for Anaplastic Lymphoma Kinase (ALK). Here, we report a case of BIA-ALCL in a 48-year-old woman post breast reconstruction. This case report is aimed at raising awareness and education on the significance of considering the development of BIA-ALCL in cases where cytology is negative and helping better understand this disease process.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3861
Author(s):  
Anand K. Deva ◽  
Suzanne D. Turner ◽  
Marshall E. Kadin ◽  
Mark R. Magnusson ◽  
H. Miles Prince ◽  
...  

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoma. Where implant history is known, all confirmed cases to date have occurred in patients with exposure to textured implants. There is a spectrum of disease presentation, with the most common occurring as a seroma with an indolent course. A less common presentation occurs as locally advanced or, rarely, as metastatic disease. Here we review the immunological characteristics of BIA-ALCL and potential triggers leading to its development. BIA-ALCL occurs in an inflammatory microenvironment with significant lymphocyte and plasma cell infiltration and a prominent Th1/Th17 phenotype in advanced disease. Genetic lesions affecting the JAK/STAT signaling pathway are commonly present. Proposed triggers for the development of malignancy include mechanical friction, silicone implant shell particulates, silicone leachables, and bacteria. Of these, the bacterial hypothesis has received significant attention, supported by a plausible biologic model. In this model, bacteria form an adherent biofilm in the favorable environment of the textured implant surface, producing a bacterial load that elicits a chronic inflammatory response. Bacterial antigens, primarily of Gram-negative origin, may trigger innate immunity and induce T-cell proliferation with subsequent malignant transformation in genetically susceptible individuals. Although much remains to be elucidated regarding the multifactorial origins of BIA-ALCL, future research should focus on prevention and treatment strategies, recognizing susceptible populations, and whether decreasing the risk of BIA-ALCL is possible.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
P. L. Moori ◽  
F. Ibison ◽  
D. Jacob ◽  
J. Iddon

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, non-Hodgkin lymphoma which arises within the capsules of breast implants. These particular tumours have expression of CD30 and are negative for Anaplastic Lymphoma Kinase (ALK). Here, we report a case of BIA-ALCL in a 48-year-old woman post breast reconstruction. This case report is aimed at raising awareness and education on the significance of considering the development of BIA-ALCL in cases where cytology is negative and helping better understand this disease process.


2019 ◽  
pp. 1-5
Author(s):  
Letícia Morais Coelho de Oliveira Sermoud ◽  
Sérgio Romano ◽  
Maurício Chveid ◽  
Gilberto Luiz da Silva Amorim

Breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare, breast implant–associated T-cell lymphoma in which CD30 is expressed and anaplastic lymphoma kinase ( ALK) expression is absent. However, despite the low risk of developing the disease, more information on BIA-ALCL is necessary, because the number of women with breast implants has been increasing worldwide; Brazil is one of the main markets for this type of implant. The objectives of this review are to clarify the issue of BIA-ALCL occurrence after risk-reducing mastectomy, to show the importance of this disease, and to raise awareness among the medical community about this rare pathologic condition. In 2016, BIA-ALCL was included by WHO in the new classification of lymphomas, and this demonstrates the attention that medical entities should give to this disease. Thus, awareness about BIA-ALCL must be broadened among the medical societies and regulatory authorities, both to foster better approaches to this disease, which should be evaluated in a multidisciplinary manner, and to provide better knowledge among health care professionals and the target population about the use of implants.


Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 107 ◽  
Author(s):  
Ivonne Montes-Mojarro ◽  
Julia Steinhilber ◽  
Irina Bonzheim ◽  
Leticia Quintanilla-Martinez ◽  
Falko Fend

Anaplastic large cell lymphoma (ALCL) represents a group of malignant T-cell lymphoproliferations that share morphological and immunophenotypical features, namely strong CD30 expression and variable loss of T-cell markers, but differ in clinical presentation and prognosis. The recognition of anaplastic lymphoma kinase (ALK) fusion proteins as a result of chromosomal translocations or inversions was the starting point for the distinction of different subgroups of ALCL. According to their distinct clinical settings and molecular findings, the 2016 revised World Health Organization (WHO) classification recognizes four different entities: systemic ALK-positive ALCL (ALK+ ALCL), systemic ALK-negative ALCL (ALK− ALCL), primary cutaneous ALCL (pC-ALCL), and breast implant-associated ALCL (BI-ALCL), the latter included as a provisional entity. ALK is rearranged in approximately 80% of systemic ALCL cases with one of its partner genes, most commonly NPM1, and is associated with favorable prognosis, whereas systemic ALK− ALCL shows heterogeneous clinical, phenotypical, and genetic features, underlining the different oncogenesis between these two entities. Recognition of the pathological spectrum of ALCL is crucial to understand its pathogenesis and its boundaries with other entities. In this review, we will focus on the morphological, immunophenotypical, and molecular features of systemic ALK+ and ALK− ALCL. In addition, BI-ALCL will be discussed.


2016 ◽  
Vol 34 (2) ◽  
pp. 160-168 ◽  
Author(s):  
Mark W. Clemens ◽  
L. Jeffrey Medeiros ◽  
Charles E. Butler ◽  
Kelly K. Hunt ◽  
Michelle A. Fanale ◽  
...  

Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL.


2014 ◽  
Vol 138 (6) ◽  
pp. 842-846 ◽  
Author(s):  
Jie Xu ◽  
Shi Wei

Primary breast anaplastic large cell lymphoma (ALCL) is rare but is more commonly seen in patients with implants; fewer than 50 cases of breast implant–associated ALCL have been reported in the English language literature. Breast implant–associated ALCL is not a disease of the breast parenchyma, but instead is a disease of the fibrous capsule surrounding the implant. The patients usually present with an effusion around the implant and, rarely, with a solid mass. Morphologically, the neoplastic cells are large, epithelioid, and pleomorphic, with abundant cytoplasm, vesicular irregular nuclei, and frequent mitoses. Occasional “hallmark” cells may be present. The lesional cells typically show strong and diffuse immunoreactivity for CD30 and often express T-cell markers, cytotoxic-associated antigens, and epithelial membrane antigen. Almost all reported cases are negative for anaplastic lymphoma kinase. Molecular genetic analyses have demonstrated T-cell receptor gene rearrangements. The differential diagnosis essentially includes poorly differentiated carcinoma, other lymphomas, and chronic inflammation. Once a diagnosis of lymphoma is established, it is important to exclude systemic anaplastic lymphoma kinase–negative ALCL involving the breast, primary cutaneous ALCL, and other CD30+ lymphoproliferative disorders. The patients with effusion-associated ALCL often have an indolent course and excellent prognosis, responding well to excision of the fibrous capsule around the implant (capsulectomy) and implant removal. In contrast, patients who present with a distinct mass may have a more aggressive course and poor prognosis, requiring chemotherapy and/or radiation therapy.


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4667
Author(s):  
Sergio Pina-Oviedo ◽  
Carlos Ortiz-Hidalgo ◽  
Adrian Alejandro Carballo-Zarate ◽  
Alejandra Zarate-Osorno

Anaplastic large cell lymphoma (ALCL) is a subtype of CD30+ large T-cell lymphoma (TCL) that comprises ~2% of all adult non-Hodgkin lymphomas. Based on the presence/absence of the rearrangement and expression of anaplastic lymphoma kinase (ALK), ALCL is divided into ALK+ and ALK-, and both differ clinically and prognostically. This review focuses on the historical points, clinical features, histopathology, differential diagnosis, and relevant cytogenetic and molecular alterations of ALK- ALCL and its subtypes: systemic, primary cutaneous (pc-ALCL), and breast implant-associated (BIA-ALCL). Recent studies have identified recurrent genetic alterations in this TCL. In systemic ALK- ALCL, rearrangements in DUSP22 and TP63 are detected in 30% and 8% of cases, respectively, while the remaining cases are negative for these rearrangements. A similar distribution of these rearrangements is seen in pc-ALCL, whereas none have been detected in BIA-ALCL. Additionally, systemic ALK- ALCL—apart from DUSP22-rearranged cases—harbors JAK1 and/or STAT3 mutations that result in the activation of the JAK/STAT signaling pathway. The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but not in pc-ALCL. Although the pathogenesis of these alterations is not fully understood, most of them have prognostic value and open the door to the use of potential targeted therapies for this subtype of TCL.


2005 ◽  
Vol 8 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Shimareet Kumar ◽  
Stefania Pittaluga ◽  
Mark Raffeld ◽  
Michael Guerrera ◽  
Nita L. Seibel ◽  
...  

We present the clinicopathologic findings in 4 children with primary cutaneous anaplastic large cell lymphoma (C-ALCL). The patients ranged in age from 13 months to 8 years, with 3 females and 1 male. All presented with a rapidly enlarging mass involving the skin and subcutaneous tissue. Histologic evaluation showed sheets of large pleomorphic lymphoid cells that were diffusely and strongly CD30+. Tumor cells were CD45+ in 1 of 4 cases. Cells were of T-cell phenotype, with variable positivity for CD3 (3 of 4 cases) and CD5 (2 of 4 cases). All 4 cases were positive for CD4 and clusterin. Staining for anaplastic lymphoma kinase was negative in all cases. No evidence of systemic involvement was noted at initial presentation or over a follow-up of 5 to 78 months, although 3 patients had cutaneous recurrences. Primary C-ALCL has only rarely been described in the pediatric population. The high-grade histologic appearance of this lymphoma belies its generally favorable clinical course and prognosis. Recognition of this entity and its differentiation from other T-cell lymphomas that secondarily involve the skin is important to avoid unnecessarily aggressive therapy in these children.


Materials ◽  
2018 ◽  
Vol 11 (12) ◽  
pp. 2393 ◽  
Author(s):  
Maria Mempin ◽  
Honghua Hu ◽  
Durdana Chowdhury ◽  
Anand Deva ◽  
Karen Vickery

Breast implantation either for cosmetic or reconstructive e purposes is one of the most common procedures performed in plastic surgery. Biofilm infection is hypothesised to be involved in the development of both capsular contracture and anaplastic large cell lymphoma (ALCL). Capsular contracture is one of the principal reasons for breast revision surgery and is characterised by the tightening and hardening of the capsule surrounding the implant, and ALCL is an indolent lymphoma found only in women with textured implants. We describe the types of breast implants available with regard to their surface characteristics of surface area and roughness and how this might contribute to capsular contracture and/or biofilm formation. The pathogenesis of capsular contracture is thought to be due to biofilm formation on the implant, which results in on-going inflammation. We describe the current research into breast implant associated ALCL and how implant properties may affect its pathogenesis, with ALCL only occurring in women with textured implants.


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