scholarly journals How I treat breast implant–associated anaplastic large cell lymphoma

Blood ◽  
2018 ◽  
Vol 132 (18) ◽  
pp. 1889-1898 ◽  
Author(s):  
Neha Mehta-Shah ◽  
Mark W. Clemens ◽  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Large Cell ◽  
World Health ◽  
Team Approach ◽  
Textured Surface ◽  
Complete Surgical Excision ◽  
Large Cell Lymphoma

Abstract Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a recently described form of T-cell non-Hodgkin lymphoma now formally recognized by the World Health Organization classification of lymphoid neoplasms. The disease most often presents with a delayed seroma around the breast implant, almost exclusively with a textured surface, and manifests with breast pain, swelling or asymmetry, capsular contracture, but can also present with a breast mass, and lymph node involvement. The prognosis of BIA-ALCL is favorable compared with many other subtypes of systemic T-cell lymphoma; however, unlike other non-Hodgkin lymphomas, complete surgical excision for localized disease is an important part of the management of these patients. In this paper, we share our recommendations for a multidisciplinary team approach to the diagnosis, workup, and treatment of BIA-ALCL in line with consensus guidelines by the National Comprehensive Cancer Network.

scholarly journals The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 107 ◽  
Author(s):  
Ivonne Montes-Mojarro ◽  
Julia Steinhilber ◽  
Irina Bonzheim ◽  
Leticia Quintanilla-Martinez ◽  
Falko Fend
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Large Cell ◽  
World Health ◽  
Anaplastic Lymphoma ◽  
Molecular Features ◽  
Starting Point ◽  
Large Cell Lymphoma

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.

scholarly journals Finding Consensus After Two Decades of Breast Implant-Associated Anaplastic Large Cell Lymphoma

2019 ◽  
Vol 33 (04) ◽  
pp. 270-278 ◽  
Author(s):  
Mark W. Clemens ◽  
Ryan C. DeCoster ◽  
Berry Fairchild ◽  
Alexander A. Bessonov ◽  
Fabio Santanelli di Pompeo
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Breast Implant ◽  
Breast Implants ◽  
Large Cell ◽  
World Health ◽  
Textured Surface ◽  
Early Stage Disease ◽  
Large Cell Lymphoma

AbstractBreast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and indolent, but potentially fatal cancer of the immune system that can develop around textured-surface breast implants. The World Health Organization first recognized BIA-ALCL as a unique clinical entity in 2016. To date, over 600 confirmed cases have been reported worldwide. BIA-ALCL most commonly presents with disease confined to the capsule, as a seroma or a mass adjacent to the implant. While BIA-ALCL has a fairly indolent clinical course, with an excellent prognosis in early stage disease, disseminated cancer and death have also been reported. In this review, the authors focus on the early diagnosis and treatment, including reconstructing the breast following BIA-ALCL, and also discuss recently updated National Comprehensive Cancer Network guidelines. They also review the current epidemiology and risk factors associated with BIA-ALCL. Finally, they discuss important medicolegal considerations and the bioethics surrounding the continued use of textured-surface breast implants.

scholarly journals 51 Small cell/lymphohistiocytic morphology is associated with CD8 positivity, retained T cell markers, a trend of decreased PD-L1 expression, but not outcome in adults with ALK+ ALCL

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A54-A54
Author(s):  
Mahsa Khanlari ◽  
Shaoying Li ◽  
Roberto N Miranda ◽  
Swaminathan Iyer ◽  
Cameron Yin ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Small Cell ◽  
Adult Patients ◽  
World Health ◽  
Proliferation Index ◽  
Cell Markers ◽  
Large Cell Lymphoma

BackgroundSeveral morphologic patterns of ALK+ anaplastic large cell lymphoma (ALCL) are recognized: common, small cell, lymphohistiocytic, Hodgkin-like, and composite patterns.1 Small cell (SC) and lymphohistiocytic (LH) patterns are thought to be closely associated with poorer outcome in children with ALK+ ALCL.2 However, the clinicopathologic and prognostic features of SC/LH patterns of ALK+ ALCL are not yet reported in adults. Recently, we found PD-L1 expression in a large subset of ALK+ ALCL cases, however, PD-L1 expression in SC/LH versus non-SC/LH ALCL has not been reported.MethodsAmong 102 adult patients with ALK+ ALCL seen at our institution from January 1, 2007 through August 30, 2018, 18 (18%) cases had a SC and/or LH pattern. The clinical, pathologic, and outcome data were compared between SC/LH and non-SC/LH ALK+ ALCL cases using Fisher’s exact test. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test.ResultsThere were no significant differences in clinical features including age, gender, nodal versus extranodal involvement, B symptoms, stage, leukocytosis/lymphocytosis, and serum LDH levels between patients with SC/LH versus non-SC/LH ALK+ ALCL. Compared to non-SC/LH cases, SC/LH ALCL was more often positive for CD2 (92% vs. 36%, p = 0.0007), CD3 (81% vs. 15%, p = 0.0001), CD7 (80% vs. 37%, p = 0.03), and CD8 (54% vs. 7%, p = 0.0006). SC/LH ALCL showed a trend of decreased PD-L1 expression than non-SC/LH cases (24% vs. 46%, p = 0.11). There were no significant differences in the expression of CD4, CD5, CD25, CD43, CD45, CD56, TCR A/B, TCR G/D, cytotoxic markers, EMA, Ki-67 proliferation index. The induction chemotherapy and response rate in patients with SC/LH ALK+ ALCL were similar to patients with non-SC/LH ALK+ ALCL. After a median follow-up of 30.5 months (range, 0.3–224 months), there was no significant difference in OS between patients with SC/LH versus non-SC/LH ALK+ ALCL (p = 0.88).ConclusionsIn adults with ALK+ALCL, the SC/LH morphologic pattern is associated with a CD8+ T cell immunophenotype and retention of expression of T cell markers (CD2, CD3, and CD7). The trend of decreased PD-L1 expression in SC/LH ALCL suggests that these patients may not be ideal candidates for PD-L1 immunotherapy. The SC/LH patterns of ALK+ ALCL have no impact on the prognosis of adult patients which is in contrast to the reported association of the SC/LH patterns with poorer outcome in children with ALK+ ALCL.Ethics ApprovalThe study was approved by the Institutional Review Board at MD Anderson Cancer Center, Approval number: PA16-0897ReferencesSwerdlow SH, Campo E, The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–2390.Brugières L, Deley MC, CD30 (+) anaplastic large-cell lymphoma in children: Analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood 1998;92:3591–3598.

scholarly journals IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas

2020 ◽  
Author(s):  
Arianna Di Napoli ◽  
Daniele Greco ◽  
Giorgia Scafetta ◽  
Francesca Ascenzi ◽  
Alessandro Gulino ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Large Cell ◽  
Mediators Of Inflammation ◽  
Cytokine Milieu ◽  
Large Cell Lymphoma ◽  
T Cell Clonality ◽  
Cell Clonality

Abstract Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL.

scholarly journals Description of Two Cases of Anaplastic Large Cell Lymphoma Associated with a Breast Implant

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Julie Crèvecoeur ◽  
Véronique Jossa ◽  
Joan Somja ◽  
Jean-Claude Parmentier ◽  
Jean-Luc Nizet ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Fluid Collection ◽  
Breast Implants ◽  
Large Cell ◽  
World Health ◽  
Breast Volume ◽  
Volume Increase ◽  
Large Cell Lymphoma

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized provisional entity in the 2017 revision of the World Health Organization classification of lymphoid neoplasms. Although the majority of the cases described in the literature demonstrate an effusion confined to the capsule of the breast implant, this rare pathology can also invade the capsule and adjacent tissues and/or involve lymph nodes. We hereby report two new cases of BIA-ALCL in a 58-year-old and a 47-year-old Caucasian female who received a silicone breast implant. The first patient showed a sudden and rapid right breast volume increase 6 years after the implantation surgery. As for the second patient, a left breast volume increase was observed also suddenly and quickly 11 years after surgery. In both cases, an uncompressed mammography was performed allowing a new approach to highlight periprosthetic fluid reaction. Pathologic examination of the fluid collection revealed atypical cells positive for CD30 and CD45 and negative for ALK and CK7. This allowed pathologists to diagnose a breast implant-associated anaplastic large cell lymphoma. Patients were treated with bilateral capsulectomy with no additional local or systemic therapy. The development of breast augmentation may come with an increase in the frequency of this pathology. Radiologists and senologists must therefore be careful when women with breast implants show an increase of breast volume and all cases of BIA-ALCL must be recorded and reported.

scholarly journals Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: Establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity

Cancer ◽  
2010 ◽  
Vol 117 (7) ◽  
pp. 1478-1489 ◽  
Author(s):  
Melissa G. Lechner ◽  
Stephen Lade ◽  
Daniel J. Liebertz ◽  
H. Miles Prince ◽  
Garry S. Brody ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Large Cell ◽  
Clinical Entity ◽  
Model Cell ◽  
Large Cell Lymphoma

scholarly journals Etiology of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Current Directions in Research

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3861
Author(s):  
Anand K. Deva ◽  
Suzanne D. Turner ◽  
Marshall E. Kadin ◽  
Mark R. Magnusson ◽  
H. Miles Prince ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Bacterial Load ◽  
Locally Advanced ◽  
Large Cell ◽  
Future Research ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

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.

Survival Analysis of Anaplastic Large Cell Lymphoma, Systemic and Cutaneous-Types: Report from the International T-Cell Lymphoma Project.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 293-293
Author(s):  
Kerry J. Savage ◽  
Julie M. Vose ◽  
Nancy Lee Harris ◽  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
World Health ◽  
Anaplastic Lymphoma ◽  
Limited Stage ◽  
Significant Difference ◽  
Large Cell Lymphoma

Abstract The WHO (World Health) Organization Classification recognizes two distinct subtypes of anaplastic large cell lymphoma: Primary systemic and Primary cutaneous types, which have differences in immunophenotype, genetics, and clinical behavior. It is now known that approximately 60% of systemic ALCLs express the anaplastic lymphoma kinase (ALK) protein (ALK-pos) and have a significantly superior survival to ALK-neg cases. Since ALK-neg ALCL appear to have a prognosis similar to peripheral T-cell lymphoma unspecified (PTCL-U), it has been suggested that they should be classified as PTCL-U. Herein, we report the clinical features of newly diagnosed systemic and cutaneous ALCL from the International T-cell Lymphoma Study Group. Materials and Methods: 186 cases of ALCL were identified by the WHO disease definitions: systemic ALCL 163 (88%) (ALK-pos 91 (56%), 72(44%) ALK-neg), and 23 (17%) cutaneous ALCL (cut ALCL). The median age of ALK-pos, ALK-neg and cut ALCL was 32, 57.5 and 54, respectively. There was a male predominance for all subtypes. Most cases of systemic ALCL presented with stage III or IV disease (64% ALK-pos, 58% ALK-neg) and in contrast, 87% of cut ALCL had localized disease. The majority of patients with systemic ALCL were treated with CHOP-type chemotherapy. Most patients with cut ALCL (91%) received additional therapy: 13 (62%) CHOP-type chemotherapy, 11(52%) chemoradiation, 4 (19%) radiation alone. Results: The 5y failure free survival (FFS) and overall survival (OS) was superior for ALK-pos ALCL (70.5% and 58%) compared to ALK-neg ALCL (49% and 36%) (p=.022 and p=.014 for FFS and OS, respectively). Comparison of ALK-pos (n=16) and ALK-neg ALCL (n=23) patients with limited stage disease (defined as stage I or II, no B symptoms and non-bulky) failed to demonstrate a significant difference in FFS (p=.54) or OS (p=.21). Both ALK-pos and ALK-neg ALCL had a superior FFS (ALK-pos p< .001; ALK-neg p=.012) and OS (ALK-pos p<.001; ALK-neg p=.032) than PTCL-U. In contrast to PTCL-U, an apparent plateau was observed on the FFS curve for ALK-neg ALCL. For cut ALCL, the 5y FFS and OS was 90% and 57%, superior to systemic ALCL. The administration of chemotherapy did not appear to impact outcome in patients with cut ALCL (p=.64). Among the prognostic factors analyzed, the international prognostic index (IPI) was the most effective for defining risk categories in ALK-neg ALCL. For ALK-pos ALCL both the IPI and anemia (Hb < 11.0 g/L) were effective in risk-group stratification in multivariate analysis. Conclusions: Similar to prior reports, ALK-pos ALCL has a superior outcome to ALK-neg ALCL. For limited stage patients, this survival difference is not apparent, suggesting that a small subgroup of patients with ALK-neg ALCL may have a more favorable prognosis, similar to ALK-pos ALCL. The IPI is effective in both ALK-neg and ALK-pos ALCL at risk stratification. Finally, contrary to prior reports, ALK-neg ALCL patients appear to have a superior outcome to PTCL-U and an apparent plateau in the FFS curve. These results suggest that ALK-neg ALCL should still be distinguished from both ALK-pos ALCL and PTCL-U.

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