Extraskeletal Osteosarcoma After Postoperative Radiotherapy for a Keloid: a Case Report

Background: The current standard treatment for keloids is a combination of surgery and postoperative radiotherapy with 8–25 Gy. Case presentation: Our case was a 75-year-old patient who developed a swollen mass in her chest 20 years after excision of a chest keloid followed by 32 Gy postoperative radiotherapy. After resection of the swollen mass, pathology indicated extraskeletal osteosarcoma. Conclusions: Six putative cases of carcinogenesis after postsurgical radiotherapy for keloid have been reported over the last 70 years. To our knowledge, this is the rst case of post-keloid radiotherapy carcinogenesis that meets the denition of a radiation-induced sarcoma. The risk of secondary carcinogenesis after postsurgical radiotherapy for keloid is small but must be explained to the patient.


Background
Keloids are raised, red, growing and spreading brotic scar tissues. They form after injury and are due to abnormal wound-healing responses. Although keloids are benign and not life-threatening, the associated pruritus and pain can be very bothersome for the patient. Surgical resection alone associates with extremely high recurrence rates [1,2]. Therefore, surgery followed by postoperative radiotherapy has become the standard treatment for keloids in recent years [1].

Case Presentation
A 75-year-old woman presented with a painful swollen mass in her chest. A biopsy was performed and the pathological evaluation revealed granulation tissue. However, approximately 2 months later, pain recurred at the same site and the mass was excised. The pathological ndings were signi cant for bone formation in the mass (Fig. 1A). There were also numerous cells in the tissue that had p53-positive nuclei and were dividing (Figs. 1B and C). Extraskeletal osteosarcoma was diagnosed.
Examination of the patient's history revealed she had undergone mastopathy at age 25 and the resulting scar had developed into a keloid. At age 55 years, the keloid was fully extirpated and 32 Gy radiation was administered. The swollen mass observed at age 75 years was located within the radiation eld (Fig. 2). Therefore, the nal diagnosis was extraskeletal osteosarcoma after radiotherapy for a keloid.
The patient was referred to our hospital for advanced specialty care. The chest skin, the sternum, and the 2nd to 7th ribs were resected (Figs. 3A and B). For reconstruction, a vertical rectus abdominis ap and an intercostal arteriovenous blood supply were employed (Fig. 3C). Pathological evaluation of the excised tissue did not demonstrate any residual tumor. The postoperative course was uneventful. After 5 years, there was no evidence of sarcoma recurrence. While a keloid developed on part of the operative scar, it was successfully treated with steroid tape.

Discussion And Conclusions
Keloids are benign but can signi cantly affect patient quality of life. Since surgical resection alone associates with recurrence rates of up to 50-80% [1,2], resection followed by postoperative radiotherapy has become the standard treatment for these scars over the last few decades. This treatment paradigm is supported by the fact that the risk of carcinogenesis from keloid radiotherapy appears to be very low: our PubMed literature search showed that over the last 70 years, only six cases of putative keloid radiotherapy-induced carcinogenesis have been reported. The tumors were brosarcoma, basal-cell carcinoma, thyroid carcinoma, breast-ductal carcinoma (two cases), and mucoepidermoid carcinoma. Five of these cases were summarized in a 2009 review [3] while the mucoepidermoid-carcinoma case was reported in 2012 [4]. The radiation doses ranged from 10.5 to 80 Gy. Three patients were children (9-13 years old) at the time of treatment. Most tumors took at least 8 years to develop. However, three cases cannot be de nitively declared to be radiation-induced carcinomas. One was the brosarcoma case, which rose unusually quickly after radiotherapy (3.5 years). Moreover, the two breast-carcinoma cases had relevant family history and a history of oral hormone therapy, respectively. Thus, carcinogenesis after keloid radiotherapy is vanishingly rare and is likely to be even rarer with current keloid-treatment regimens, which carefully apply radiation at moderate doses of 8-25 Gy and stringently avoid treating children [5].
Radiation-induced sarcomas were de ned by Cahan et al. in 1948 [5]; the de nition was then modi ed by Arlen et al. in 1971 [6]. Thus, a tumor is considered to be a radiation-induced sarcoma if (i) its histology differs from that the primary tumor that required radiotherapy, (ii) it lies within the therapeutic irradiation area, and (iii) the duration between radiotherapy and tumor detection is relatively long. Our case meets all of these criteria and thus appears to be the rst reported case of keloid radiotherapy-induced extraskeletal osteosarcoma.
In our case, the radiotherapy dose was 32 Gy, which is greater than current keloid-radiotherapy doses.
Thus, the risk of extraskeletal osteosarcoma after this therapy is very low. Nevertheless, this case indicates that we should be aware that radiation therapy for keloids does carry a risk of carcinogenesis. Patients with keloids should be told of this risk and advised that long-term follow-up will be required if they undergo keloid resection followed by radiotherapy.

Declarations
Ethics approval and consent to participate According to the Ethics Committee of Keio University School of Medicine, Japan, case studies do not require ethical approval for publication. The patient was treated according to the tenets of the Declaration of Helsinki.

Consent for publication
Written informed consent was obtained from the patient for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in Chief of this journal.

Availability of data and materials
The datasets used during the current study are available from the corresponding author on reasonable request.

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