Breast prosthetic implant-associated Squamous Cell Carcinoma: A case report and Literature Review

Breast reconstruction is widely used for women undergoing mastectomy. Prosthetic implants have become a common technique performed for these women because of their safety, exibility and adjustable size. There are few reports of implant-associated squamous cell carcinoma. In addition to this report, only 8 reports including 11 cases have been reported in the English literature. We report the case of a patient with breast prosthetic implant-associated squamous cell carcinoma who received mastectomy and prosthetic implants 10 years ago. She was recently hospitalized with unilateral breast enlargement. Surgical pathology showed squamous cell carcinoma around the breast implant. There was no evidence of primary squamous cell carcinoma at any other anatomic site. We analysed all 11 patients with breast implant-derived squamous cell carcinoma (SCC) from a thorough literature search to identify studies. The median age of patients at SCC diagnosis was 56.8 years old. The average time from initial breast augmentation until SCC diagnosis was 21.9 years. The prognosis was poor; 4 of the 11 patients eventually progressed or died within 1 year, 3 of the 11 patients were disease free during the follow-up period, and 4 of the 11 patients were lost to follow-up. The most widespread opinion is that chronic inammation from breast implants plays a substantial role in the disease progression of SCC. We reported the rare complications associated with breast prosthetic implants and reviewed the literature. This malignancy should be taken into account in patients with breast prosthetic implants who have acute breast pain and enlargement.


Background
Breast reconstruction after mastectomy improves quality of life and patient satisfaction. Implant-based breast reconstruction is the most popular choice in post-mastectomy women, accounting for 65% of all breast reconstructions in the USA [1][2][3]. It is relatively easy to learn and popularize because there is no need for another incision during the operation, and it also has the advantages of quick postoperative recovery, minimal trauma, and few complications [4,5]. It has been reported that the main complications include 4% infection, 2.5% skin ap necrosis, 2% seroma, and 3.8% capsular contracture [6,7]. Limited evidence of cancer caused by the prosthesis has been reported. However, here, we report a case of implant-associated squamous cell carcinoma (SCC). The patient received prosthetic implants 10 years ago, and she had acute unilateral breast pain and enlargement due to tumours arising on the posterior implant.

Case Presentation
A 45-year-old woman had a past medical history of invasive ductal carcinoma status post-mastectomy and reconstruction in 2008. She was hospitalized in June 2018 and presented with left breast swelling and enlargement for 7 days. She denied recent fever, chills, nausea, vomiting or breast trauma. She also denied erythema and tenderness around the area, and she did not have nipple discharge. Upon physical examination, a round hard mass with a diameter of approximately 6 cm was palpated in the inner upper quadrant of the left breast near the sternum. Ten years ago, the patient received a modi ed radical mastectomy for breast cancer, followed by breast reconstruction with prosthetic implants immediately. The prosthetic implants chosen were drop-shaped silicone prostheses. Postoperatively, she recovered well without complications such as infection or skin changes. Her surgical pathology at that time showed invasive ductal carcinoma of the left breast (Table 1). She received 6 cycles of anthracyclines and docetaxel (speci c drug and dose unknown), followed by tamoxifen endocrine therapy for 3 years post-chemotherapy. Follow-up surveillance with breast ultrasound and mammography during the last 6 months revealed no abnormalities. At this visit, considering her breast cancer history and physical examination, CT and MRI were performed to evaluate the possibility of recurrence ( Fig. 1). Enhanced metabolic signal changes under the left pectoralis major near the armpit and at the left supraclavicular lymph nodes suggested metastasis. Ultrasound-guided core needle biopsy of the left chest wall mass demonstrated squamous cell carcinoma. The decision was made to proceed with left chest wall mass resection, prosthesis removal and left supraclavicular lymph node biopsy. Surgical pathology of the left chest wall near the armpit mass suggested poorly differentiated SCC ( Fig. 2 & Fig. 3). The morphology and immunohistochemistry showed squamous cell carcinoma ( Table 2). Table 2 Pathology and IHC of the Local-regional recurrent focus Left chest wall mass Pathology: a poorly differentiated carcinoma, morphology and immunohistochemistry showed squamous cell carcinoma differentiation.
adjuvant therapy GP regimen for 6 cycles, local and regional radiotherapy after GP chemotherapy, and capecitabine monotherapy was continued to maintain 8 cycles after radiotherapy, followed by OFS combined with oral anastrozole to date.
Postoperatively, she underwent chemotherapy with gemcitabine combined with a carboplatin (GP) regimen for 6 cycles with no signi cant progress. Local and regional radiotherapy treatments were given after GP chemotherapy, and capecitabine monotherapy was continued to maintain 8 cycles after radiotherapy, followed by OFS combined with oral anastrozole to date. The patient is currently in a stable condition with no signi cant progress until October 2020.

Discussion And Conclusions
There have been few reports of malignant tumours related to breast implants. In addition to this report, only 11 cases of implant-associated SCC have been reported since 1992. As shown in Table 3, all of these reported patients had a long history of breast silicone implantation (> 10 years), and the average time from initial breast augmentation until SCC diagnosis was 21.9 years. The median age of patients at SCC diagnosis was 56.8 years old. The tumour had an aggressive course of prognosis; 4 of the 11 patients eventually progressed or died within 1 year, 3 of the 11 patients were disease free during the follow-up period, and 4 of the 11 patients were lost to follow-up. Here, we present a patient with SCC that developed from an implant capsule 10 years after breast reconstruction, and she had stable condition at the 2-year follow-up after being diagnosed with SCC. Our patient presented to the clinic initially due to abnormal breast augmentation. The suspected causes included recurrent cancer and implant rupture. According to the reported literature, the chances of capsule rupture are commonly increased 10-15 years after placement because the mean lifespan of an implant is approximately 13 years [8]. Imaging studies were used to diagnose implant-associated SCC in our patient. We diagnosed this woman with implant-associated SCC by imaging and pathological examination. Further, we suggested primary SCC of the breast instead of metastasis.
Primary SCC of the breast is a rare tumour, accounting for an estimated frequency of 0.1-3.6% of all invasive breast cancers with poor clinical outcomes [9][10][11]. Skin or nipple cancer and metastasis sites should be excluded when SCC is diagnosed [12]. The clinical symptoms of implant-associated SCC are likely to be a primary mammary tumour, and the histological appearance is important to make the diagnosis [13,14]. In this report, the woman had no histologic indications of primary breast cancer, as she had a mastectomy 10 years ago. The cancer was located around the squamous epithelialized implant capsules and involved the chest wall through the capsule. Moreover, there was no clinical or radiologic evidence of cutaneous or distant invasive squamous cell carcinoma.
The pathogenesis of breast prosthetic implant-associated SCC is not clear. Metaplastic squamous epithelialization of the capsular lining or entrapment of skin or adnexal elements has been acknowledged [15]. The most common histological characterization in implant capsules was collagen bre alignment and brous capsule [16,17]. A silicone implant leads to the formation of a nonadherent surface, and a textured and rough surface may stimulate immunity, therefore enhancing the risk of an in ammatory response [8] . Squamous epithelialization metaplasia may act as a protective mechanism against chronic injury from breast implant placement. In this report, the woman had no evidence of chronic infection.
This study obtained approval from the Ethics Committee of the Shandong Cancer Hospital and Institute and was approved to meet the standard of clinical practice. The consent was received from the study participants and the guidelines outlined in the Declaration of Helsinki were followed.

Competing interests
The authors declare that they have no competing interests.