Breast Implant-Associated Bilateral B-Cell Lymphoma

Breast Implant-Associated Bilateral B-Cell Lymphoma Abstract Lymphomas associated with implants are predominantly of T-cell type—with anaplastic large cell lymphoma (ALCL) being most reported. That said, to date, 6 cases of B-cell lymphoma associated with breast implants have been reported. All cases exhibited unilateral breast involvement. Here, the authors report a case of low-grade B-cell lymphoma occurring bilaterally in a 34-year-old woman with a history of Poly Implant Prosthese silicone implants at age 20, T-cell angioimmunoblastic lymphoma, and subsequent myeloablative double cord blood transplantation. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, with very low Ki-67 of 1%. Nevertheless, cases of ALCL associated with breast implants are rare but much more documented in the literature than B-cell lymphomas associated with breast implants, as in this patient. Identification of a relationship between breast cancer and silicone is still ongoing in the literature, with long-term clinical follow up required. More research will be necessary to fully characterize the occurrence, course, and association of this disease with breast implants in order to properly guide diagnosis and management. Level of Evidence: 5 The first cosmetic breast augmentation began in 1895 when Czerny transplanted a lipoma from the hip of a patient to repair a surgical defect in the breast.1,2 In 1962, plastic surgeons Thomas Cronin and Frank Gerow developed the first silicone, gel-filled breast prosthesis.2,3 Silicone implants have since been successfully utilized for breast augmentation and reconstruction in millions of women around the world. Until recently, evidence in the literature demonstrated no increased risk of malignancy associated with breast implants. However, since the 1990s, isolated cases of anaplastic large cell lymphoma (ALCL) have fueled increasing concern, and in 2016, the World Health Organization provisionally classified breast implant-associated ALCL (BIA-ALCL) as a newly recognized entity and highlighted the importance of surgical management of the disease. Primary breast lymphoma is extremely rare (0.5% of all breast malignancies) and mostly of B-cell type.4 On the other hand, lymphomas associated with implants are predominantly of T-cell type, and ALCL has been the most reported. That said, to date there have been 6 reported cases of B-cell lymphoma associated with breast implants,5-10 with two cases of large B-cell lymphoma (Table 1).9,10 All 6 cases showed only unilateral involvement. Therefore, here we report a case of a B-cell lymphoma occurring bilaterally in a patient with a history of breast augmentation, recurrent capsular contractures, and T-cell lymphoma. Table 1. Reported Cases of B-Cell Lymphomas Associated With Breast Implants Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% View Large Table 1. Reported Cases of B-Cell Lymphomas Associated With Breast Implants Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% View Large CASE REPORT A 34-year-old woman presented in June 2017 with a history of bilateral breast augmentations initially placed in 2003 at 20 years old; she had revisions and enlargement of Poly Implant Prosthese (PIP) silicone implants, which have been plagued by recurrent capsular contracture and pain issues. Of note, the patient also has a history of T-cell angioimmunoblastic lymphoma and underwent myeloablative double cord blood transplantation and total body irradiation in December 2010. Her T-cell lymphoma remains in remission, and she has been off all immunosuppression for several years. A bilateral capsulectomy and implant exchange was undergone in May 2012, with negative pathology. Pain resolved but contracture recurred in 2015 leading to left implant exchange and capsulectomy with negative pathology and benign fibrous capsule. Mild chronic inflammation was noted both times. In 2016, the patient’s left implant displaced, which was corrected, but she returned to the operating room in June 2017 for a left breast open partial capsulectomy and removal with replacement of the silicone implant and placement of AlloDerm. Biopsy of the partial capsulectomy specimen from this surgery showed small B-lymphocytes with low proliferation index (1%). The low-grade B-cell lymphoma involved the left chest wall under the left breast implant. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, with very low Ki-67 of 1%. Bone marrow biopsy showed no evidence of lymphomatous involvement. Positron emission tomography-computed tomography scan showed multiple small bilateral lymph nodes with low level of fluorodeoxyglucose uptake. There was no other new adenopathy suggestive of recurrent lymphoma. Complete blood count with differential in July 2017 showed no lymphocytosis with a white blood cell count of 8.1 with 46.9% lymphocytes and 43.4% neutrophils, red blood cell count of 3.97, hemoglobin of 11.6, immunoglobin G level in serum was 1094, and lactate dehydrogenase level in blood was 144. MRI of her breast was obtained and reviewed in preparation for bilateral completion capsulectomies since only part of the capsule was removed during her recent surgery, and to remove both breast implants as well as the Alloderm (Figure 1). The patient’s hematologist discussed treatment options with the patient, which included observation without further intervention vs treatment with IV rituximab weekly for 4 weeks. The patient’s case was discussed at the institution’s breast and lymphoma tumor boards. The tumor board’s recommendation was for mastectomy on the left. The patient requested bilateral mastectomies for symmetry, so she underwent bilateral sentinel lymph node biopsy, total capsulectomies bilaterally, explantation of implants, and total mastectomies (Figure 2). Final pathology from this procedure (Figures 3-4) demonstrated low-grade B-cell lymphoma involving the right breast capsule and focally the left breast capsule, similar to that seen in the previous left capsulectomy specimen from June. Figures 5 and 6 demonstrate additional pathology with CD20 staining and CD10 staining, respectively. Immunoglobulin clonality done by polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded material was done on both right and left breast. Immunoglobulin heavy chain and kappa light chain were not detected via PCR. The B-cell infiltrate revealed weak and focal co-expression of CD23 and CD5, without proliferation centers and LEF-1 staining. Patient was negative for Epstein Barr virus. A bone marrow study was negative for small lymphocytic leukemia and chronic lymphocytic leukemia. As of the last follow-up appointment in November 30, 2017, she has gone on to recover well from the surgery and is getting rituximab for further treatment. Written informed consent has been obtained for this case and its photographs. Figure 1. View largeDownload slide (A) Bilateral breast MRI showing a plaque-like enhancement of the left upper lateral implant surface, suspicious for newly diagnosed lymphoma, in a (B) 34-year-old woman ultimately diagnosed with low-grade B-cell lymphoma. Figure 1. View largeDownload slide (A) Bilateral breast MRI showing a plaque-like enhancement of the left upper lateral implant surface, suspicious for newly diagnosed lymphoma, in a (B) 34-year-old woman ultimately diagnosed with low-grade B-cell lymphoma. Figure 2. View largeDownload slide Removal of capsule, implants, and remnant breast tissue and nipples. Figure 2. View largeDownload slide Removal of capsule, implants, and remnant breast tissue and nipples. Figure 3. View largeDownload slide (A) Low-power 2× magnification view and (B) 10× magnification view from biopsy of bilateral breast capsules showing low grade B-cell lymphoma involving the fibrous capsule. Figure 3. View largeDownload slide (A) Low-power 2× magnification view and (B) 10× magnification view from biopsy of bilateral breast capsules showing low grade B-cell lymphoma involving the fibrous capsule. Figure 4. View largeDownload slide (A-D) High-power 40× magnification views from biopsy demonstrating histomorphology of B-cell lymphoma. Figure 4. View largeDownload slide (A-D) High-power 40× magnification views from biopsy demonstrating histomorphology of B-cell lymphoma. Figure 5. View largeDownload slide (A-D) View from biopsy with CD20 immunostaining. Figure 5. View largeDownload slide (A-D) View from biopsy with CD20 immunostaining. Figure 6. View largeDownload slide View from biopsy with CD10 immunostaining. Figure 6. View largeDownload slide View from biopsy with CD10 immunostaining. DISCUSSION The first silicone implants were produced in 196211 and have since retained a controversial safety profile. Since then, both silicone and saline implants have undergone considerable evolution with several changes and improvements.12 Silicone has been reported to be both safe13 and associated with a plethora of side effects, including localized and distant granulomatous inflammation, reactive lymphadenopathy, and nephropathy.1,5,14 Manufactured silicone contains several components that are biologically reactive, such as residual vinyl groups, which can reach adjacent tissues by rupture or seepage over time.14-16 While this might suggest a “foreign-body carcinogenesis,”16 Brinton reported in 2007 that there is “no convincing evidence that breast implants alter the risk of non-breast malignancies.”17 Of note, our patient’s initial implant material was produced by PIP, once the world’s third-largest producer of silicone implants whose products were banned in 2010 after it was discovered that they used industrial-grade silicone. While not documented in the literature, a British woman was reported in the media in 2012 to have died of lymphoma after a ruptured PIP implant.18 Currently the most common lymphoma associated with breast implants, ALCL is still extremely rare relative to overall rates of breast malignancies. While a direct causation has not been established, case reports of ALCL are increasing, among reports of lymphomas in general associated with breast implants.16 As in many of the previous cases, this patient’s implants were compromised and she experienced complications with capsular contracture. However, what is distinct about this case is the bilateral nature of the diagnosed lymphoma, as a B-cell lymphoma of the same type was incidentally found on the contralateral side. This is unique compared to the other six other reported cases of unilateral B-cell lymphoma associated with breast implants (Table 1). The question arises as to when and in which instance is it appropriate to perform a diagnostic test on a woman with breast implants? As such, this case, as well as those listed in Table 1, represent few among the overall population. This report is limited by its inability to be applied to the general population, as well as the expected bias in the literature to report unique cases. Further large-scale studies are required to establish the link between B-cell lymphomas and breast implants, much in the same way that studies on BIA-ALCL have led to its current National Comprehensive Cancer Network (NCCN) classification and guidelines. Furthermore, although immunoglobulin heavy and kappa light chain rearrangements were not detected in this patient, a negative immunoglobulin PCR test does not entirely rule out a monoclonal B-cell proliferation. According to Kokovic et al, the sensitivity of a combined light and heavy chain assay was 81.1%.19 While a positive test would have further aided in diagnosing the low-grade B-cell lymphoma, the negative result does not rule out lymphoma. Other possible reasons for a negative result could be due to a false negative, especially given that the sensitivity of the test is not 100%, sampling error, or oligoclonal proliferation. Importantly, our patient presents with an additional history of a T-cell lymphoma diagnosis starting in 2010 with subsequent blood cord transplantation and irradiation. Secondary cancer is known to be a great concern for cancer survivors. While in remission, this history may play a role in development of her current lymphoma as well as serve as a limitation in this case in establishing a clear link between the breast implants and current B-cell lymphoma diagnosis. It is possible that this patient’s B-cell lymphoma stems from her prior risk, given her prior history of a rare T-cell lymphoma,20,21 instead of her breast implants. According to the new NCCN BIA-ALCL guidelines, timely diagnosis and complete surgical excision of lymphoma, implants, and the surrounding fibrous capsule is the optimal approach for management of BIA-ALCL.22 Similarly, it has been recommended that until there is a better diagnostic test, late periprosthetic seromas (> 6 months after surgery) without a history of trauma should be collected and submitted for cytology for culture.9 More research will be necessary to fully characterize the occurrence, course, and association of this disease with breast implants to properly guide diagnosis and management. CONCLUSION In conclusion, we present a case of a patient with bilateral breast implant-associated B-cell lymphoma after a history of T-cell angioimmunoblastic lymphoma in remission from 2010. While there exist multiple reports of BIA-ALCL in the literature,14,16,22 reports of B-cell lymphoma associated with breast implants are few. As discussion of breast implant-associated lymphoma continues, it is our hope that this case study motivates future research on establishing a clear link between breast implants and lymphoma. Disclosures The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. Yang N , Muradali D . The augmented breast: a pictorial review of the abnormal and unusual . AJR Am J Roentgenol . 2011 ; 196 ( 4 ): W451 - W460 . Google Scholar CrossRef Search ADS PubMed 2. Maxwell GP , Gabriel A . The evolution of breast implants . Clin Plast Surg . 2009 ; 36 ( 1 ): 1 - 13, v . Google Scholar CrossRef Search ADS PubMed 3. Peters W , Fornasier V . Complications from injectable materials used for breast augmentation . Can J Plast Surg . 2009 ; 17 ( 3 ): 89 - 96 . Google Scholar CrossRef Search ADS PubMed 4. Surov A , Holzhausen HJ , Wienke A et al. Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features . Br J Radiol . 2012 ; 85 ( 1014 ): e195 - e205 . Google Scholar CrossRef Search ADS PubMed 5. Cook PD , Osborne BM , Connor RL , Strauss JF . Follicular lymphoma adjacent to foreign body granulomatous inflammation and fibrosis surrounding silicone breast prosthesis . Am J Surg Pathol . 1995 ; 19 ( 6 ): 712 - 717 . Google Scholar CrossRef Search ADS PubMed 6. Kraemer DM , Tony HP , Gattenlöhner S , Müller JG . Lymphoplasmacytic lymphoma in a patient with leaking silicone implant . Haematologica . 2004 ; 89 ( 4 ): ELT01 . Google Scholar PubMed 7. Said JW , Tasaka T , Takeuchi S et al. Primary effusion lymphoma in women: report of two cases of Kaposi’s sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women . Blood . 1996 ; 88 ( 8 ): 3124 - 3128 . Google Scholar PubMed 8. Nichter LS , Mueller MA , Burns RG , Stallman JM . First report of nodal marginal zone B-cell lymphoma associated with breast implants . Plast Reconstr Surg . 2012 ; 129 ( 3 ): 576e - 578e . Google Scholar CrossRef Search ADS PubMed 9. Smith BK , Gray SS . Large B-cell lymphoma occurring in a breast implant capsule . Plast Reconstr Surg . 2014 ; 134 ( 4 ): 670e - 671e . Google Scholar CrossRef Search ADS PubMed 10. Moling O , Piccin A , Tauber M et al. Intravascular large B-cell lymphoma associated with silicone breast implant, HLA-DRB1*11:01, and HLA-DQB1*03:01 manifesting as macrophage activation syndrome and with severe neurological symptoms: a case report . J Med Case Rep . 2016 ; 10 ( 1 ): 254 . Google Scholar CrossRef Search ADS PubMed 11. Cronin TD , Brauer RO . Augmentation mammaplasty . Surg Clin North Am . 1971 ; 51 ( 2 ): 441 - 452 . Google Scholar CrossRef Search ADS PubMed 12. Tanne JH . FDA approves silicone breast implants 14 years after their withdrawal . BMJ . 2006 ; 333 ( 7579 ): 1139 . Google Scholar PubMed 13. Duteille F , Perrot P , Bacheley MH , Stewart S . Eight-year safety data for round and anatomical silicone gel breast implants . Aesthet Surg J . 2018 ; 38 ( 2 ): 151 - 161 . Google Scholar CrossRef Search ADS PubMed 14. Ravi-Kumar S , Sanaei O , Vasef M , Rabinowitz I , Fekrazad MH . Anaplastic large cell lymphoma associated with breast implants . World J Plast Surg . 2012 ; 1 ( 1 ): 30 - 35 . Google Scholar PubMed 15. Institute of Medicine (US) Committee on the Safety of Silicone Breast Implants ; Bondurant S , Ernster V , Herdman R , editors. Safety of Silicone Breast Implants . Washington (DC) : National Academies Press (US) ; 1999 . 4, Silicone Toxicology. Available from: https://www.ncbi.nlm.nih.gov/books/NBK44789. 16. Rupani A , Frame JD , Kamel D . Lymphomas associated with breast implants: a review of the literature . Aesthet Surg J . 2015 ; 35 ( 5 ): 533 - 544 . Google Scholar CrossRef Search ADS PubMed 17. Brinton LA . The relationship of silicone breast implants and cancer at other sites . Plast Reconstr Surg . 2007 ; 120 ( 7 Suppl 1 ): 94S - 102S . Google Scholar CrossRef Search ADS PubMed 18. British woman could be first to have died of cancer caused by ruptured PIP breast impant. Mirror . July 1, 2012 . http://www.mirror.co.uk/news/uk-news/british-woman-could-be-first-to-have-died-946842. Accessed September 21, 2014 . 19. Kokovic I , Jezersek Novakovic B , Novakovic S . Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas . Int J Oncol . 2015 ; 46 ( 3 ): 953 - 962 . Google Scholar CrossRef Search ADS PubMed 20. Armitage JO . The aggressive peripheral T-cell lymphomas: 2017 . Am J Hematol . 2017 ; 92 ( 7 ): 706 - 715 . Google Scholar CrossRef Search ADS PubMed 21. Lunning MA , Vose JM . Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma . Blood . 2017 ; 129 ( 9 ): 1095 - 1102 . Google Scholar CrossRef Search ADS PubMed 22. Clemens MW , Horwitz SM . NCCN Consensus Guidelines for the Diagnosis and Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma . Aesthet Surg J . 2017 ; 37 ( 3 ): 285 - 289 . Google Scholar CrossRef Search ADS PubMed © 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Aesthetic Surgery Journal Oxford University Press

Breast Implant-Associated Bilateral B-Cell Lymphoma

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© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com
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Abstract

Abstract Lymphomas associated with implants are predominantly of T-cell type—with anaplastic large cell lymphoma (ALCL) being most reported. That said, to date, 6 cases of B-cell lymphoma associated with breast implants have been reported. All cases exhibited unilateral breast involvement. Here, the authors report a case of low-grade B-cell lymphoma occurring bilaterally in a 34-year-old woman with a history of Poly Implant Prosthese silicone implants at age 20, T-cell angioimmunoblastic lymphoma, and subsequent myeloablative double cord blood transplantation. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, with very low Ki-67 of 1%. Nevertheless, cases of ALCL associated with breast implants are rare but much more documented in the literature than B-cell lymphomas associated with breast implants, as in this patient. Identification of a relationship between breast cancer and silicone is still ongoing in the literature, with long-term clinical follow up required. More research will be necessary to fully characterize the occurrence, course, and association of this disease with breast implants in order to properly guide diagnosis and management. Level of Evidence: 5 The first cosmetic breast augmentation began in 1895 when Czerny transplanted a lipoma from the hip of a patient to repair a surgical defect in the breast.1,2 In 1962, plastic surgeons Thomas Cronin and Frank Gerow developed the first silicone, gel-filled breast prosthesis.2,3 Silicone implants have since been successfully utilized for breast augmentation and reconstruction in millions of women around the world. Until recently, evidence in the literature demonstrated no increased risk of malignancy associated with breast implants. However, since the 1990s, isolated cases of anaplastic large cell lymphoma (ALCL) have fueled increasing concern, and in 2016, the World Health Organization provisionally classified breast implant-associated ALCL (BIA-ALCL) as a newly recognized entity and highlighted the importance of surgical management of the disease. Primary breast lymphoma is extremely rare (0.5% of all breast malignancies) and mostly of B-cell type.4 On the other hand, lymphomas associated with implants are predominantly of T-cell type, and ALCL has been the most reported. That said, to date there have been 6 reported cases of B-cell lymphoma associated with breast implants,5-10 with two cases of large B-cell lymphoma (Table 1).9,10 All 6 cases showed only unilateral involvement. Therefore, here we report a case of a B-cell lymphoma occurring bilaterally in a patient with a history of breast augmentation, recurrent capsular contractures, and T-cell lymphoma. Table 1. Reported Cases of B-Cell Lymphomas Associated With Breast Implants Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% View Large Table 1. Reported Cases of B-Cell Lymphomas Associated With Breast Implants Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% Study Age (yr) Sex Implant Implant compromised Capsular contracture Lymphoma type (WHO classification) Location Time from implantation to lymphoma (years) Presentation Immunohistochemical analysis Cook et al, 1995 56 F Silicone Yes, leakage Yes Follicular lymphoma Left breast, medial to implant and bone marrow 6 2-cm palpable nodule BCL-2, unknown Said et al, 1996 46 F Silicone No Not reported Primary effusion lymphoma Right breast within capsule 5 Swelling in right breast, fluid surrounding implant within capsule CD30, CD43, CD45 Kraemer et al, 2004 55 F Silicone Yes, leakage Not reported Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia Bone marrow 25 (implants removed after 17) Low-grade fevers, enlarged lymph node, monoclonal gammopathy CD19, HLA DR, CD27, IgM (CD5, CD10 negative) Nichter et al, 2012 58 F Saline silicone Yes, rupture Yes Nodal marginal zone lymphoma; follicular lymphoma Left axilla 20 since saline, 9 since silicone 3-cm palpable lymph node, fatigue BCL-2, CD10, CD20 (CD5 negative) Smith et al, 2014 83 F Silicone No Yes Large B-cell lymphoma Right breast within capsule 44 (placed after mastectomy for phylloides tumor) Swelling in right breast, fluid surrounding implant within capsule CD20, CD45 Moling et al, 2016 48 F Silicone No Not reported Intravascular large B-cell lymphoma Right breast within capsule 1 (first placed 4 years prior after mastectomy for intraductal carcinoma) Diagnosis of HLH; 3 episodes of fever (starting 8 months prior), splenomegaly; histological exam showed extensive lymphohistiocytic/giant cell foreign body reaction CD20, CD5, BCL-6, BCL-1 Ki-67 > 90% Present study 34 F Silicone Yes, bottomed out Yes Low-grade B-cell lymphoma Right and left breast within capsule 14 Recurrent capsular contracture, multiple capsulectomies CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, Ki-67 1% View Large CASE REPORT A 34-year-old woman presented in June 2017 with a history of bilateral breast augmentations initially placed in 2003 at 20 years old; she had revisions and enlargement of Poly Implant Prosthese (PIP) silicone implants, which have been plagued by recurrent capsular contracture and pain issues. Of note, the patient also has a history of T-cell angioimmunoblastic lymphoma and underwent myeloablative double cord blood transplantation and total body irradiation in December 2010. Her T-cell lymphoma remains in remission, and she has been off all immunosuppression for several years. A bilateral capsulectomy and implant exchange was undergone in May 2012, with negative pathology. Pain resolved but contracture recurred in 2015 leading to left implant exchange and capsulectomy with negative pathology and benign fibrous capsule. Mild chronic inflammation was noted both times. In 2016, the patient’s left implant displaced, which was corrected, but she returned to the operating room in June 2017 for a left breast open partial capsulectomy and removal with replacement of the silicone implant and placement of AlloDerm. Biopsy of the partial capsulectomy specimen from this surgery showed small B-lymphocytes with low proliferation index (1%). The low-grade B-cell lymphoma involved the left chest wall under the left breast implant. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, with very low Ki-67 of 1%. Bone marrow biopsy showed no evidence of lymphomatous involvement. Positron emission tomography-computed tomography scan showed multiple small bilateral lymph nodes with low level of fluorodeoxyglucose uptake. There was no other new adenopathy suggestive of recurrent lymphoma. Complete blood count with differential in July 2017 showed no lymphocytosis with a white blood cell count of 8.1 with 46.9% lymphocytes and 43.4% neutrophils, red blood cell count of 3.97, hemoglobin of 11.6, immunoglobin G level in serum was 1094, and lactate dehydrogenase level in blood was 144. MRI of her breast was obtained and reviewed in preparation for bilateral completion capsulectomies since only part of the capsule was removed during her recent surgery, and to remove both breast implants as well as the Alloderm (Figure 1). The patient’s hematologist discussed treatment options with the patient, which included observation without further intervention vs treatment with IV rituximab weekly for 4 weeks. The patient’s case was discussed at the institution’s breast and lymphoma tumor boards. The tumor board’s recommendation was for mastectomy on the left. The patient requested bilateral mastectomies for symmetry, so she underwent bilateral sentinel lymph node biopsy, total capsulectomies bilaterally, explantation of implants, and total mastectomies (Figure 2). Final pathology from this procedure (Figures 3-4) demonstrated low-grade B-cell lymphoma involving the right breast capsule and focally the left breast capsule, similar to that seen in the previous left capsulectomy specimen from June. Figures 5 and 6 demonstrate additional pathology with CD20 staining and CD10 staining, respectively. Immunoglobulin clonality done by polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded material was done on both right and left breast. Immunoglobulin heavy chain and kappa light chain were not detected via PCR. The B-cell infiltrate revealed weak and focal co-expression of CD23 and CD5, without proliferation centers and LEF-1 staining. Patient was negative for Epstein Barr virus. A bone marrow study was negative for small lymphocytic leukemia and chronic lymphocytic leukemia. As of the last follow-up appointment in November 30, 2017, she has gone on to recover well from the surgery and is getting rituximab for further treatment. Written informed consent has been obtained for this case and its photographs. Figure 1. View largeDownload slide (A) Bilateral breast MRI showing a plaque-like enhancement of the left upper lateral implant surface, suspicious for newly diagnosed lymphoma, in a (B) 34-year-old woman ultimately diagnosed with low-grade B-cell lymphoma. Figure 1. View largeDownload slide (A) Bilateral breast MRI showing a plaque-like enhancement of the left upper lateral implant surface, suspicious for newly diagnosed lymphoma, in a (B) 34-year-old woman ultimately diagnosed with low-grade B-cell lymphoma. Figure 2. View largeDownload slide Removal of capsule, implants, and remnant breast tissue and nipples. Figure 2. View largeDownload slide Removal of capsule, implants, and remnant breast tissue and nipples. Figure 3. View largeDownload slide (A) Low-power 2× magnification view and (B) 10× magnification view from biopsy of bilateral breast capsules showing low grade B-cell lymphoma involving the fibrous capsule. Figure 3. View largeDownload slide (A) Low-power 2× magnification view and (B) 10× magnification view from biopsy of bilateral breast capsules showing low grade B-cell lymphoma involving the fibrous capsule. Figure 4. View largeDownload slide (A-D) High-power 40× magnification views from biopsy demonstrating histomorphology of B-cell lymphoma. Figure 4. View largeDownload slide (A-D) High-power 40× magnification views from biopsy demonstrating histomorphology of B-cell lymphoma. Figure 5. View largeDownload slide (A-D) View from biopsy with CD20 immunostaining. Figure 5. View largeDownload slide (A-D) View from biopsy with CD20 immunostaining. Figure 6. View largeDownload slide View from biopsy with CD10 immunostaining. Figure 6. View largeDownload slide View from biopsy with CD10 immunostaining. DISCUSSION The first silicone implants were produced in 196211 and have since retained a controversial safety profile. Since then, both silicone and saline implants have undergone considerable evolution with several changes and improvements.12 Silicone has been reported to be both safe13 and associated with a plethora of side effects, including localized and distant granulomatous inflammation, reactive lymphadenopathy, and nephropathy.1,5,14 Manufactured silicone contains several components that are biologically reactive, such as residual vinyl groups, which can reach adjacent tissues by rupture or seepage over time.14-16 While this might suggest a “foreign-body carcinogenesis,”16 Brinton reported in 2007 that there is “no convincing evidence that breast implants alter the risk of non-breast malignancies.”17 Of note, our patient’s initial implant material was produced by PIP, once the world’s third-largest producer of silicone implants whose products were banned in 2010 after it was discovered that they used industrial-grade silicone. While not documented in the literature, a British woman was reported in the media in 2012 to have died of lymphoma after a ruptured PIP implant.18 Currently the most common lymphoma associated with breast implants, ALCL is still extremely rare relative to overall rates of breast malignancies. While a direct causation has not been established, case reports of ALCL are increasing, among reports of lymphomas in general associated with breast implants.16 As in many of the previous cases, this patient’s implants were compromised and she experienced complications with capsular contracture. However, what is distinct about this case is the bilateral nature of the diagnosed lymphoma, as a B-cell lymphoma of the same type was incidentally found on the contralateral side. This is unique compared to the other six other reported cases of unilateral B-cell lymphoma associated with breast implants (Table 1). The question arises as to when and in which instance is it appropriate to perform a diagnostic test on a woman with breast implants? As such, this case, as well as those listed in Table 1, represent few among the overall population. This report is limited by its inability to be applied to the general population, as well as the expected bias in the literature to report unique cases. Further large-scale studies are required to establish the link between B-cell lymphomas and breast implants, much in the same way that studies on BIA-ALCL have led to its current National Comprehensive Cancer Network (NCCN) classification and guidelines. Furthermore, although immunoglobulin heavy and kappa light chain rearrangements were not detected in this patient, a negative immunoglobulin PCR test does not entirely rule out a monoclonal B-cell proliferation. According to Kokovic et al, the sensitivity of a combined light and heavy chain assay was 81.1%.19 While a positive test would have further aided in diagnosing the low-grade B-cell lymphoma, the negative result does not rule out lymphoma. Other possible reasons for a negative result could be due to a false negative, especially given that the sensitivity of the test is not 100%, sampling error, or oligoclonal proliferation. Importantly, our patient presents with an additional history of a T-cell lymphoma diagnosis starting in 2010 with subsequent blood cord transplantation and irradiation. Secondary cancer is known to be a great concern for cancer survivors. While in remission, this history may play a role in development of her current lymphoma as well as serve as a limitation in this case in establishing a clear link between the breast implants and current B-cell lymphoma diagnosis. It is possible that this patient’s B-cell lymphoma stems from her prior risk, given her prior history of a rare T-cell lymphoma,20,21 instead of her breast implants. According to the new NCCN BIA-ALCL guidelines, timely diagnosis and complete surgical excision of lymphoma, implants, and the surrounding fibrous capsule is the optimal approach for management of BIA-ALCL.22 Similarly, it has been recommended that until there is a better diagnostic test, late periprosthetic seromas (> 6 months after surgery) without a history of trauma should be collected and submitted for cytology for culture.9 More research will be necessary to fully characterize the occurrence, course, and association of this disease with breast implants to properly guide diagnosis and management. CONCLUSION In conclusion, we present a case of a patient with bilateral breast implant-associated B-cell lymphoma after a history of T-cell angioimmunoblastic lymphoma in remission from 2010. While there exist multiple reports of BIA-ALCL in the literature,14,16,22 reports of B-cell lymphoma associated with breast implants are few. As discussion of breast implant-associated lymphoma continues, it is our hope that this case study motivates future research on establishing a clear link between breast implants and lymphoma. Disclosures The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. Yang N , Muradali D . The augmented breast: a pictorial review of the abnormal and unusual . AJR Am J Roentgenol . 2011 ; 196 ( 4 ): W451 - W460 . Google Scholar CrossRef Search ADS PubMed 2. Maxwell GP , Gabriel A . The evolution of breast implants . Clin Plast Surg . 2009 ; 36 ( 1 ): 1 - 13, v . Google Scholar CrossRef Search ADS PubMed 3. Peters W , Fornasier V . Complications from injectable materials used for breast augmentation . Can J Plast Surg . 2009 ; 17 ( 3 ): 89 - 96 . Google Scholar CrossRef Search ADS PubMed 4. Surov A , Holzhausen HJ , Wienke A et al. Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features . Br J Radiol . 2012 ; 85 ( 1014 ): e195 - e205 . Google Scholar CrossRef Search ADS PubMed 5. Cook PD , Osborne BM , Connor RL , Strauss JF . Follicular lymphoma adjacent to foreign body granulomatous inflammation and fibrosis surrounding silicone breast prosthesis . Am J Surg Pathol . 1995 ; 19 ( 6 ): 712 - 717 . Google Scholar CrossRef Search ADS PubMed 6. Kraemer DM , Tony HP , Gattenlöhner S , Müller JG . Lymphoplasmacytic lymphoma in a patient with leaking silicone implant . Haematologica . 2004 ; 89 ( 4 ): ELT01 . Google Scholar PubMed 7. Said JW , Tasaka T , Takeuchi S et al. Primary effusion lymphoma in women: report of two cases of Kaposi’s sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women . Blood . 1996 ; 88 ( 8 ): 3124 - 3128 . Google Scholar PubMed 8. Nichter LS , Mueller MA , Burns RG , Stallman JM . First report of nodal marginal zone B-cell lymphoma associated with breast implants . Plast Reconstr Surg . 2012 ; 129 ( 3 ): 576e - 578e . Google Scholar CrossRef Search ADS PubMed 9. Smith BK , Gray SS . Large B-cell lymphoma occurring in a breast implant capsule . Plast Reconstr Surg . 2014 ; 134 ( 4 ): 670e - 671e . Google Scholar CrossRef Search ADS PubMed 10. Moling O , Piccin A , Tauber M et al. Intravascular large B-cell lymphoma associated with silicone breast implant, HLA-DRB1*11:01, and HLA-DQB1*03:01 manifesting as macrophage activation syndrome and with severe neurological symptoms: a case report . J Med Case Rep . 2016 ; 10 ( 1 ): 254 . Google Scholar CrossRef Search ADS PubMed 11. Cronin TD , Brauer RO . Augmentation mammaplasty . Surg Clin North Am . 1971 ; 51 ( 2 ): 441 - 452 . Google Scholar CrossRef Search ADS PubMed 12. Tanne JH . FDA approves silicone breast implants 14 years after their withdrawal . BMJ . 2006 ; 333 ( 7579 ): 1139 . Google Scholar PubMed 13. Duteille F , Perrot P , Bacheley MH , Stewart S . Eight-year safety data for round and anatomical silicone gel breast implants . Aesthet Surg J . 2018 ; 38 ( 2 ): 151 - 161 . Google Scholar CrossRef Search ADS PubMed 14. Ravi-Kumar S , Sanaei O , Vasef M , Rabinowitz I , Fekrazad MH . Anaplastic large cell lymphoma associated with breast implants . World J Plast Surg . 2012 ; 1 ( 1 ): 30 - 35 . Google Scholar PubMed 15. Institute of Medicine (US) Committee on the Safety of Silicone Breast Implants ; Bondurant S , Ernster V , Herdman R , editors. Safety of Silicone Breast Implants . Washington (DC) : National Academies Press (US) ; 1999 . 4, Silicone Toxicology. Available from: https://www.ncbi.nlm.nih.gov/books/NBK44789. 16. Rupani A , Frame JD , Kamel D . Lymphomas associated with breast implants: a review of the literature . Aesthet Surg J . 2015 ; 35 ( 5 ): 533 - 544 . Google Scholar CrossRef Search ADS PubMed 17. Brinton LA . The relationship of silicone breast implants and cancer at other sites . Plast Reconstr Surg . 2007 ; 120 ( 7 Suppl 1 ): 94S - 102S . Google Scholar CrossRef Search ADS PubMed 18. British woman could be first to have died of cancer caused by ruptured PIP breast impant. Mirror . July 1, 2012 . http://www.mirror.co.uk/news/uk-news/british-woman-could-be-first-to-have-died-946842. Accessed September 21, 2014 . 19. Kokovic I , Jezersek Novakovic B , Novakovic S . Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas . Int J Oncol . 2015 ; 46 ( 3 ): 953 - 962 . Google Scholar CrossRef Search ADS PubMed 20. Armitage JO . The aggressive peripheral T-cell lymphomas: 2017 . Am J Hematol . 2017 ; 92 ( 7 ): 706 - 715 . Google Scholar CrossRef Search ADS PubMed 21. Lunning MA , Vose JM . Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma . Blood . 2017 ; 129 ( 9 ): 1095 - 1102 . Google Scholar CrossRef Search ADS PubMed 22. Clemens MW , Horwitz SM . NCCN Consensus Guidelines for the Diagnosis and Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma . Aesthet Surg J . 2017 ; 37 ( 3 ): 285 - 289 . Google Scholar CrossRef Search ADS PubMed © 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Aesthetic Surgery JournalOxford University Press

Published: May 29, 2018

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