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D. Olsen, G. Keeney, Beiyun Chen, D. Visscher, J. Carter (2017)
Breast implant capsule-associated squamous cell carcinoma: a report of 2 cases.Human pathology, 67
Brinton La, Brown Sl (1997)
Breast Implants and CancerJournal of the National Cancer Institute, 89
S. Kitchen, W. Bauer, C. Paletta, S. Shehadi (1994)
Epithelialization of the lining of a breast implant capsule. Possible origin of squamous cell carcinoma associated with a breast implant capsuleCancer, 73
Jose Peña-Salcedo, M. Soto-Miranda, José López-Salguero (2012)
Back to the Future: A 15-Year Experience With Polyurethane Foam-Covered Breast Implants Using the Partial-Subfascial TechniqueAesthetic Plastic Surgery, 36
E. Noels, O. Lapid, J. Lindeman, E. Bastiaannet (2015)
Breast implants and the risk of breast cancer: a meta-analysis of cohort studies.Aesthetic surgery journal, 35 1
Terri Zomerlei, Amin Samarghandi, A. Terando (2015)
Primary Squamous Cell Carcinoma Arising from a Breast Implant CapsulePlastic and Reconstructive Surgery Global Open, 3
M. Molitor, O. Mestak, L. Kalinová, A. Krajcová, J. Mesták (2014)
The history and safety of breast implants.Acta chirurgiae plasticae, 56 1-2
D. deCamara (1994)
Rupture and aging of silicone gel breast implants.Plastic and reconstructive surgery, 93 7
M. Boer, F. Leeuwen, M. Hauptmann, L. Overbeek, J. Boer, N. Hijmering, Arthur Sernee, C. Klazen, M. Lobbes, R. Hulst, H. Rakhorst, D. Jong (2018)
Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the BreastJAMA Oncology, 4
H. Wagner, F. Beller, M. Pfautsch (1977)
ELECTRON AND LIGHT MICROSCOPY EXAMINATION OF CAPSULES AROUND BREAST IMPLANTSPlastic and Reconstructive Surgery, 60
Bonnie Balzer, S. Weiss (2009)
Do biomaterials cause implant-associated mesenchymal tumors of the breast? Analysis of 8 new cases and review of the literature.Human pathology, 40 11
C. Paletta, Francis Palette, F. Paletta (1992)
Squamous cell carcinoma following breast augmentation.Annals of plastic surgery, 29 5
E. Doren, R. Miranda, J. Selber, P. Garvey, Jun Liu, L. Medeiros, Charles Butler, M. Clemens (2017)
U.S. Epidemiology of Breast Implant–Associated Anaplastic Large Cell LymphomaPlastic and Reconstructive Surgery, 139
J. Philip (1982)
Squamous cell carcinoma arising at the site of an underlying bullet.Journal of the Royal College of Surgeons of Edinburgh, 27 6
J. Thomsen, L. Christensen, M. Nielsen, B. Brandt, V. Breiting, S. Felby, Erik Nielsen (1990)
Histologic Changes and Silicone Concentrations in Human Breast Tissue Surrounding Silicone Breast ProsthesesPlastic and Reconstructive Surgery, 85
A. Siddons (1962)
Cell Type in the Choice of Cases of Carcinoma of the Bronchus for Surgery *Thorax, 17
Abstract Squamous cell carcinoma (SCC) arising from the breast is an exceedingly rare disease; even more rare is SCC arising from a breast implant capsule. So far, only five cases have been reported in the literature. We present the case of a 65-year-old woman with a remote history of breast augmentation using foam covered silicone implants performed in 1979. In 2010, she presented with progressive enlargement of her left breast with associated pain. Mammographic and sonographic evaluation demonstrated fluid surrounding the implant without evidence of abnormal masses. She subsequently underwent explantation of the silicone implant, capsulectomy, and revision augmentation with a saline implant. Final pathology demonstrated a fibrous pseudocapsule exhibiting squamous metaplasia giving rise to a well-differentiated SCC invading skeletal muscle. A thorough literature review was performed to identify studies with breast implant-derived SCC. Four studies, involving five patients were included. The mean age of reported patients at the time of diagnosis was 59.8 years old. The average time from initial breast augmentation to diagnosis of breast implant capsule SCC was 23.2 years. Two of the five patients eventually expired due to the disease process. Whether or not there is a true association between SCC and breast implants is unknown. Although it is currently deemed a rare finding, it’s believed that chronic inflammation/irritation from the breast implant and transection of the epithelium-lined ducts play a major role in development of the disease process. Level of Evidence: 5 Primary breast augmentation or implant-based reconstruction is a common surgical procedure with more than one million implants placed per year.1 Despite the initial concerns of the FDA in the 1990s regarding case reports linking silicone breast implants to autoimmune diseases, silicone-based implants regained their approval for use after a thorough review and panel discussion in 2006.2 To date, implant-associated mesenchymal carcinomas and/or sarcomas are exceedingly rare.3 However, a recent study has shown that anaplastic large cell lymphoma (ALCL) is a relatively rare, yet real complication following the use of textured breast implants.4 This recent ALCL study has proved that the full spectrum of breast augmentation complications is not well defined outside the known complications of infection, rupture, hematoma, and capsular contracture. Likewise, Doren et al published the first US population-based report which demonstrated the absolute risk of developing breast implant-associated ALCL.5 This study determined that the risk was significantly increased with the use of textured implants.5 Here, we report a case of squamous cell carcinoma (SCC) arising from a breast implant capsule, a review of the literature, and key clinical findings that are similar amongst all of these reported cases. CASE REPORT The reported case is of a 65-year-old woman who presented to The Georgia Institute for Plastic Surgery in Savannah, GA with an enlarging left breast after a mechanical fall after slipping while at home in 2010. Her history included a subglandular bilateral breast augmentation in 1975 with the placement of a 200 cc foam-covered silastic implants (Hyer Schulte). Initial examination of her left breast, in February 2010, revealed a breast mound that was approximately twice the size of the right and extremely tender to palpation (Figure 1A). A mammogram was performed which showed edema vs hemorrhage around the left breast implant with superior extravasation of silicone material (Figure 2A). An ultrasound was also performed which revealed a circumferential hypoechogenicity concerning for edema vs hemorrhage without a defined mass. Figure 1. View largeDownload slide (A) Initial examination (2010) showing an enlarged left breast as compared to the right. (B) Photograph taken at 8-year follow up (2018) after undergoing left radical mastectomy with medial chest wall resection and postoperative radiation therapy. Figure 1. View largeDownload slide (A) Initial examination (2010) showing an enlarged left breast as compared to the right. (B) Photograph taken at 8-year follow up (2018) after undergoing left radical mastectomy with medial chest wall resection and postoperative radiation therapy. Figure 2. View largeDownload slide (A) Mammogram of the left breast in 2010, showing circumferential hypoechogenicity around the implant without a discrete mass. The hypoechogenicity is highly concerning for edema and/or hemorrhage around the implant. (B) Gross anatomical specimen of the breast implant capsule in 2010. The arrows point to areas on the capsule with suspected invasive SCC. On gross examination (not pictured), the breast implant was ruptured. Figure 2. View largeDownload slide (A) Mammogram of the left breast in 2010, showing circumferential hypoechogenicity around the implant without a discrete mass. The hypoechogenicity is highly concerning for edema and/or hemorrhage around the implant. (B) Gross anatomical specimen of the breast implant capsule in 2010. The arrows point to areas on the capsule with suspected invasive SCC. On gross examination (not pictured), the breast implant was ruptured. The decision was then made to perform a complete capsulectomy with implant exchange via an inframammary approach. Intraoperatively, a periprosthetic milky fluid collection was encountered. This was aspirated and sent for ALCL CD-markers and histological examination. The implant capsule and ruptured implant were completely removed and sent for permanent pathology (Figure 2B). The posterior capsule was well adhered to the underlying pectoralis major musculature. The implant pocket was thoroughly irrigated and a new 375 cc saline implant was placed. The histology of the aspirated fluid revealed keratinized squamous cells (Figure 3A). The implant capsule had well-differentiated SCC arising from the fibrous capsule (Figure 3B). Figure 3. View largeDownload slide (A) Histological examination of the milky periprosthetic fluid showing keratinized squamous cells. (B) Histological examination of the breast implant capsule showing well differentiated, invasive squamous cell carcinoma arising from the fibrous capsule. Figure 3. View largeDownload slide (A) Histological examination of the milky periprosthetic fluid showing keratinized squamous cells. (B) Histological examination of the breast implant capsule showing well differentiated, invasive squamous cell carcinoma arising from the fibrous capsule. Upon follow up one-month later, the breast incision was well healed. A positron-emission tomography (PET) scan was performed and showed fluorodeoxyglucose (FDG) uptake surrounding the left breast implant, axillary lymph nodes, and internal mammary lymph node chain (Figure 4). At that time, the patient elected to undergo a left radical mastectomy and medial chest wall resection (Figure 5). She received postoperative radiation therapy of 50 Gy. After an 8-year follow up (in 2018), the patient remained alive and disease free (Figure 1B). Figure 4. View largeDownload slide A coronal and axial image of the patient’s positron-emission tomography scan, in 2010, showing fluorodeoxyglucose uptake surrounding the left breast implant, axillary lymph nodes, and internal mammary lymph node chain. Figure 4. View largeDownload slide A coronal and axial image of the patient’s positron-emission tomography scan, in 2010, showing fluorodeoxyglucose uptake surrounding the left breast implant, axillary lymph nodes, and internal mammary lymph node chain. Figure 5. View largeDownload slide Gross anatomical specimen of the patient’s left radical mastectomy with medial chest wall resection. Figure 5. View largeDownload slide Gross anatomical specimen of the patient’s left radical mastectomy with medial chest wall resection. METHODS Study Selection Three reviewers (P.J.B., V.K.C., R.J.G.) conducted a literature search within the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial databases in January 2018. All manuscripts published, with English as the primary language, were identified. A combination of the following MeSH terms were used to conduct the search: “breast capsule,” “implant capsule,” “breast implant,” “breast augmentation,” “breast implant capsule,” and “squamous cell carcinoma.” The three reviewers (P.J.B., V.K.C., R.J.G.) independently performed each step in the study selection process. Cross-referencing initial articles found via the initial keyword searches allowed for the identification of additional manuscripts. Manuscripts were included if they met the following criteria: (1) comparative retrospective studies, prospective reports, case reports, and clinical trials that reported primary SCC of a breast implant capsule; and (2) reported cases with prior history of breast augmentation. Studies were excluded if the SCC arose from within the breast parenchyma itself or the subjects did not have a prior breast augmentation. No specific time period was used as an exclusion factor. All articles were screened regardless of year published. Data Extraction From the included studies, the three reviewers (P.J.B., V.K.C., R.J.G.) independently assessed the quality and methodology of each study meeting the inclusion criteria. These manuscripts were then further analyzed looking at patient age at diagnosis, interventions, and associated outcome/complications/follow up. RESULTS Search Results Initial search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial databases using the aforementioned keywords yielded five articles. After the selection process using the inclusion and exclusion criteria detailed above, four studies were deemed eligible for inclusion in our analysis. These four studies were comprised of case reports. Primary Outcome Analysis The four included studies had five combined patients. The mean age of reported patients at the time of diagnosis was 59.8 years (range, 52-81 years). The average time from initial breast augmentation to diagnosis of breast implant capsule SCC was 23.2 years (range, 15-42 years). Two of the five patients eventually expired due to the disease process. One patient was reported as disease free at the 12-month follow up. The other two patients did not have a follow up reported. Two patients had Heyer-Schulte silicone implants, one patient had textured saline implants, one patient had smooth round silicone implants, and one patient had silicone implants, although it was not defined if these were smooth or textured, at the time of the SCC diagnosis. Patient characteristics of the literature review are summarized in Table 1. Table 1. Review of the Literature Detailing Characteristics of the Five Previously Reported Cases Study No. of patients Age (years) Reason for implantation Type of implant Time until SCC diagnosis Therapeutic treatment Outcome Patient follow up Paletta et al8 1 52 Cosmetic Heyer Schulte silicone implant 16 years Radical mastectomy Not reported Disease free at 12-month follow up Zomerlei et al9 1 58 Cosmetic Smooth silicone implant 15 years Radical mastectomy Not reported Not reported Olsen et al10 2 56 Cosmetic Textured saline implant 18 years Mastectomy with chemotherapy Local regional metastases Palliative care at 1-month follow up 81 Breast reconstruction status post benign lesion excision Unknown silicone implant 42 years Mastectomy Distant metastases Distant metastases at 5-month and eventual death Kitchen et al11 1 52 Cosmetic Heyer Schulte silicone implant 25 years Modified radical mastectomy Not reported Not reported Study No. of patients Age (years) Reason for implantation Type of implant Time until SCC diagnosis Therapeutic treatment Outcome Patient follow up Paletta et al8 1 52 Cosmetic Heyer Schulte silicone implant 16 years Radical mastectomy Not reported Disease free at 12-month follow up Zomerlei et al9 1 58 Cosmetic Smooth silicone implant 15 years Radical mastectomy Not reported Not reported Olsen et al10 2 56 Cosmetic Textured saline implant 18 years Mastectomy with chemotherapy Local regional metastases Palliative care at 1-month follow up 81 Breast reconstruction status post benign lesion excision Unknown silicone implant 42 years Mastectomy Distant metastases Distant metastases at 5-month and eventual death Kitchen et al11 1 52 Cosmetic Heyer Schulte silicone implant 25 years Modified radical mastectomy Not reported Not reported s/p, status post. View Large Table 1. Review of the Literature Detailing Characteristics of the Five Previously Reported Cases Study No. of patients Age (years) Reason for implantation Type of implant Time until SCC diagnosis Therapeutic treatment Outcome Patient follow up Paletta et al8 1 52 Cosmetic Heyer Schulte silicone implant 16 years Radical mastectomy Not reported Disease free at 12-month follow up Zomerlei et al9 1 58 Cosmetic Smooth silicone implant 15 years Radical mastectomy Not reported Not reported Olsen et al10 2 56 Cosmetic Textured saline implant 18 years Mastectomy with chemotherapy Local regional metastases Palliative care at 1-month follow up 81 Breast reconstruction status post benign lesion excision Unknown silicone implant 42 years Mastectomy Distant metastases Distant metastases at 5-month and eventual death Kitchen et al11 1 52 Cosmetic Heyer Schulte silicone implant 25 years Modified radical mastectomy Not reported Not reported Study No. of patients Age (years) Reason for implantation Type of implant Time until SCC diagnosis Therapeutic treatment Outcome Patient follow up Paletta et al8 1 52 Cosmetic Heyer Schulte silicone implant 16 years Radical mastectomy Not reported Disease free at 12-month follow up Zomerlei et al9 1 58 Cosmetic Smooth silicone implant 15 years Radical mastectomy Not reported Not reported Olsen et al10 2 56 Cosmetic Textured saline implant 18 years Mastectomy with chemotherapy Local regional metastases Palliative care at 1-month follow up 81 Breast reconstruction status post benign lesion excision Unknown silicone implant 42 years Mastectomy Distant metastases Distant metastases at 5-month and eventual death Kitchen et al11 1 52 Cosmetic Heyer Schulte silicone implant 25 years Modified radical mastectomy Not reported Not reported s/p, status post. View Large DISCUSSION Breast augmentation has been considered a very safe and effective operation enjoyed by millions of women since the early 1960s. In 1970, polyurethane foam-coated implants appeared on the market and gained popularity because the rate of capsular contracture was quite low. In the 1980s there was concern that the degradation of the polyurethane bore a relationship with breast cancer. The polyurethane foam coated implant was subsequently removed from the market in 1991.6 There has been little evidence to support that breast implants increase the risk of developing breast cancer according to the National Cancer Institute.7 However, there has been growing concern of an association between ALCL and silicone breast implants. A large new study has shown that ALCL is of growing concern associated with only textured breast implants. First reported in 1997, it is now believed that there are over 506 cases of implant-associated ALCL worldwide.4 Primary SCC arising from the capsule of a breast implant is also believed to be exceedingly rare with only four case reports available within the current literature.8-11 First described in 1992, all of the case reports currently in the literature, in addition to the case report presented within this article, share a very similar clinical presentation. This clinical presentation includes a patient who has a history of a prior breast augmentation who presents with an acute onset of unilateral breast pain and enlargement/swelling. This unusual clinical presentation and location of the SCC likely contribute to a delay in recognition and diagnosis. In an era of growing concern for breast implant-associated ALCL; one must be aware of other disease processes that can occur from an implant capsule. The question still remains, however, how does such an acellular capsule differentiate into SCC? One such theory involves the implantation of microscopic epithelial fragments during the time of prosthesis placement. These microscopic fragments would then proliferate and form an epithelial lining. However, with this theory one would expect to encounter deep-seated inclusion cysts postoperatively which have not been encountered, anecdotally, in the authors’ experience. Another theory that is better supported within the literature involves chronic inflammation resulting in metaplasia and ultimately SCC. The literature contains multiple studies that report surrounding tissue reactions which cause the formation of a fibrous capsule with the infiltration of chronic inflammatory cells and a foreign body giant cell reaction.12-14 During a breast augmentation, whether subglandular, submuscular, or dual plane, a portion of the mammary ducts are transected. These ducts are lined with epithelium. Squamous metaplasia of endoderm-derived epithelium is a common reaction to chronic inflammation in other parts of the body including bronchial epithelium, prostatic ducts, and the thyroid gland. Such chronic inflammation/irritation from the breast implant could result in the metaplastic response of the transected epithelial-line ducts resulting in the proliferation and differentiation into SCC. Likewise, the epithelial cells that line the implant pocket undergo years of chronic inflammation/irritation and could result in metaplasia and ultimately SCC. SCC arising from areas of long-standing inflammation is not novel. Marjolin’s ulcers are SCC that result from an area of skin that has sustained chronic irritation. Likewise, SCC can result from chronic osteomyelitis with a draining sinus tract. There have also been reports of SCC arising from areas of foreign body reactions in both the lung and buttock.15,16 Whether or not there is a true association between SCC and breast implants is unknown. Although it is currently deemed a rare finding, it’s believed that chronic inflammation/irritation from the breast implant and transection of the epithelium-lined ducts play a major role in development of the disease process. Unlike ALCL, the above literature review did not find a true association of implant-derived SCC with the sole use of textured implants. The limitations to this study include those that are inherent in the four included studies. The four included studies were all case reports. Likewise, each of the five patients seemed to have been treated with vastly different approaches. This spectrum bias may limit the universality of these reported findings and makes it difficult at this time to determine a universal treatment algorithm. CONCLUSION It is prudent for all surgeons to have a keen eye for any patient with a remote history of breast augmentation who then presents with an acutely enlarged and painful breast. More data will become available as the patient population with breast implants continues to age. Until the data on long-term implications of augmentation mammoplasty can be trended, there must be due vigilance in regard to postoperative changes of the breast. 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. Noels EC, Lapid O, Lindeman JH, Bastiaannet E. Breast implants and the risk of breast cancer: a meta-analysis of cohort studies. Aesthet Surg J . 2015; 35( 1): 55- 62. Google Scholar CrossRef Search ADS PubMed 2. Molitor M, Měšťák O, Kalinová L, Krajcová A, Měšťák J. 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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)
Aesthetic Surgery Journal – Oxford University Press
Published: Apr 6, 2018
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