eISSN: 2081-2841
ISSN: 1689-832X
Journal of Contemporary Brachytherapy
Current Issue Archive Supplements Articles in Press Journal Information Aims and Scope Editorial Office Editorial Board Register as Author Register as Reviewer Instructions for Authors Abstracting and indexing Subscription Advertising Information Links
SCImago Journal & Country Rank

vol. 14
Case report

Radiation-induced undifferentiated spindle cell sarcoma following high-dose-rate interstitial brachytherapy for tongue squamous cell carcinoma

Yuka Uchimoto
Hiroaki Shimamoto
1, 2
Ami Takeshita
Kaori Oya
Mitsunobu Kishino
Yasuo Fukuda
Satoru Toyosawa
Michio Oda
Kazuhiko Ogawa
Sven Kreiborg
6, 7
Sanjay M. Mallya
Shumei Murakami
1, 2

Department of Oral and Maxillofacial Radiology, Osaka University Graduate School of Dentistry, Osaka, Japan
Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
Clinical Laboratory, Osaka University Dental Hospital, Osaka, Japan
Department of Oral Pathology, Osaka University Graduate School of Dentistry, Osaka, Japan
Department of Medical Technology, Osaka University Hospital, Osaka, Japan
Department of Pediatric Dentistry and Clinical Genetics, School of Dentistry, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
3D Craniofacial Image Research Laboratory (School of Dentistry, University of Copenhagen; Centre of Head and Orthopedics, Copenhagen University Hospital Rigshospitalet; and Department of Applied Mathematics and Computer Science, Technical University of Denmark), Copenhagen, Denmark
Section of Oral and Maxillofacial Radiology, UCLA School of Dentistry, Los Angeles, USA
J Contemp Brachytherapy 2022; 14, 3: 268-272
Online publish date: 2022/05/11
Article file
- Radiation-induced.pdf  [0.36 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero


Among oral cancers, tongue cancer is most prevalent, with histopathological findings showing squamous cell carcinoma (SCC) to be responsible for 90% of these cancers. While surgical resection is considered to be the standard treatment for tongue cancer [1], radiation therapy may be utilized in some cases because of its’ advantages regarding the preservation of function and morphology. Previous studies have noted three-year local control rates following interstitial brachytherapy (ISBT) for tongue cancer of 82-84% [2, 3]. Both low-dose-rate ISBT (LDR-ISBT) and high-dose-rate ISBT (HDR-ISBT) are available. The advantages of LDR-ISBT include its’ simplicity, low level of anesthesia required, and low cost of the apparatus. Among its’ disadvantages are the operator cannot avoid being exposed to radiation, a shielded room is required for long-term patient irradiation, and dose distribution cannot be changed. HDR-ISBT overcomes these disadvantages, with irradiation time of only a few minutes, and it has recently come to be considered one of the most effective treatments for oral cancer [3]. It is important to note that radiation therapy has some side effects. Those occurring early during irradiation for oral cancer treatment include stomatitis and taste disorders, while late side effects include soft-tissue ulcers and osteonecrosis [4]. However, radiation-induced malignancy is probably the most serious complication affecting long-term survivors [5]. There is no consensus definition of radiation-induced malignancy, but the most important point is to distinguish it from recurrence. Therefore, the minimum requirement for diagnosis is a long period between the initial treatment and the occurrence of a new malignancy, and recently presented criteria include a latency period of several years [6, 7]. Furthermore, if a histopathological finding of a new malignancy is different from previous initial cancer, it is considered to be a radiation-induced malignancy [8]. Several reports of radiation-induced malignancy due to external beam radiation have been presented [9], while there are few reported cases following brachytherapy [10]. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer. The purpose of this study was to document information of a patient with tongue SCC, who was successfully treated with radiation therapy, but developed a radiation-induced undifferentiated spindle cell sarcoma of the tongue five years and one month later. Furthermore, a pseudo-tumor developed between the time of radiation exposure and the development of undifferentiated spindle cell sarcoma.

Case report

A 39-year-old woman visited our hospital with pain on the right side of her tongue. A clinical photograph showing a reddish irregular mass lesion in the right lateral border of tongue is presented in Figure 1, while T2-weighted magnetic resonance imaging (MRI) results showing a tumor sized 24 × 14 × 22 mm at the right lateral border of tongue (yellow arrows) are presented in Figure 2. Based on the biopsy and imaging results, the patient was diagnosed with SCC (cT3N0M0, stage III). A computed tomography (CT) scan was acquired, and a three-dimensional treatment plan was performed using Oncentra Brachy (Elekta AB, Stockholm, Sweden). The contour of clinical target volume (CTV) was identified using CT images. Planning target volume (PTV) was defined as an equivalent to CTV. We delivered 6 Gy as D100, i.e., minimum dose of the prescribed dose that was given to 100% of PTV. The patient underwent HDR-ISBT (60 Gy, 10 fractions, 10 flexible applicator tubes, double-plane) for 8 days, performed on the right side of the tongue (Figure 3). During follow-up, the patient noticed a mass lesion in the right side of the floor of the mouth three years and one month after the completion of therapy (Figure 4). An elevated lesion on the right side of the floor of the mouth was resected five months later, and based on surgical specimen, it was histopathologically diagnosed as high-grade dysplasia of the mucosa with suspicion of reactive hyperplasia. The tumor consisted of spindle-shaped atypical cells without malignancy (Figure 5). It was thought that the tumor was a reactive granulation containing atypical stromal cells caused by radiation, since the patient had a history of radiation. The lesion was small and superficial, with no apparent invasion into deeper muscle layers, and the shape was outwardly protruding.
After five years and one month of follow-up after radiation therapy, re-growth of a lesion with induration on the right lateral border of tongue was observed (Figures 6 and 7). A total glossectomy, rectus abdominis muscle flap reconstruction, partial mandibulectomy, scapular reconstruction, and bilateral radical neck dissection were performed. The histopathological diagnosis was an undifferentiated spindle cell sarcoma (T4aN0M0) (Figure 8). One year and ten months after the surgery, there was no obvious recurrence or metastasis (Figure 9).


According to criteria for radiation-induced malignancy presented by Sakai et al. [8], such induced cancer can be classified into three groups (A, B, and C) based on the histopathology, organ of origin, latency period, and irradiation field (Table 1). This classification is based on a definition of multiple primary malignancies presented by Warren and Gates [11]. This definition is considered to be very reliable, as it includes histopathological findings. The present case was classified as having an A2 reliability level, with a latency period of five years, which is consistent with the definition put forward by Sakai et al. Other studies have adopted the criteria for osteosarcoma presented by Cahan et al. [12] (widely used for the diagnosis of a radiation-induced sarcoma) and described a latency period of two years [6, 7]. In the present case, the latent period was five years and one month, which is also consistent with the definition. The patient’s initial malignancy was a SCC. Following radiation therapy, a pseudo-tumor was detected with no evidence of malignancy. Considering that undifferentiated spindle cell sarcoma is a rare disease, it seems appropriate to conclude that it was induced by radiation therapy in the present patient.
A radiation-induced pseudo-tumor develops earlier than sarcoma, with a median latent period of 79 months [13]. Although both sarcoma and a pseudo-tumor can be induced by radiation, it remains unclear whether a pseudo-tumor represents the precursor stage of a sarcoma [14]. A literature review of radiation-induced sarcoma showed that median age at diagnosis of radiation-induced sarcomas of the head and neck was 52 years (inter-quartile range, 21.5 years), with a mean latency between initial radiation therapy treatment and diagnosis of 11.1 years (range, 1.3-38 years) noted in one study [5], and 11.5 years (range, 6-17 years) reported by another [9].
The rates of occurrence of radiation-induced sarcomas in the head and neck range from 0.14% to 1.8% in the analyzed cases, including reports of external beam radiation therapy and LDR-ISBT [9, 10, 15]. The present case is the first reported instance of malignancy induced after HDR-ISBT in a patient treated at our hospital, and a search of the literature revealed no other report of radiation-induced malignancy development following that procedure. According to a retrospective study of radiation therapy for oral SCC, a radiation-induced pseudo-tumor is considered to be a rare complication, with a prevalence of only 0.02% [13].


Here, we report a case of a suspected radiation-induced malignancy occurring at the site of HDR-ISBT performed for tongue SCC.


The authors report no conflict of interest.


1. NCCN Clinical Practice Guidelines in Oncology Head and Neck cancers version 1.2022. 2021. Available online: https://www.nccn.org (accessed on 21th February 2022).
2. Akiyama H, Yoshida K, Shimizutani K et al. Dose reduction trial from 60 Gy in 10 fractions to 54 Gy in 9 fractions schedule in high-dose-rate interstitial brachytherapy for early oral tongue cancer. J Radiat Res 2012; 53: 722-726.
3. Yamazaki H, Inoue T, Yoshida K et al. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate. J Radiat Res 2003; 44: 37-40.
4. Hall EJ, Giaccia AJ. Radiobiology for the radiologist. 7th ed. Lippincott Williams & Wilkins, Philadelphia 2012.
5. Coca-Pelaz A, Mäkitie AA, Strojan P et al. Radiation-induced sarcomas of the head and neck: a systematic review. Adv Ther 2020; 38: 90-108.
6. Bjerkehagen B, Smeland S, Walberg L et al. Radiation-induced sarcoma: 25-year experience from the Norwegian Radium Hospital. Acta Oncol 2008; 47: 1475-1482.
7. Brady MS. Radiation-associated sarcoma of bone and soft tissue. Arch Surg 1992; 127: 1379-1385.
8. Sakai K, Hinata H, Kitamura T et al. A survey on radiation-induced cancer following radiotherapy in Japan. J Japan Radiol Soc 1981; 41: 24-32 (in Japanese).
9. Makimoto Y, Yamamoto S, Takano H et al. Imaging findings of radiation-induced sarcoma of the head and neck. Br J Radiol 2007; 80: 790-797.
10. Amemiya K, Shibuya H, Yoshimura R et al. The risk of radiation-induced cancer in patients with squamous cell carcinoma of the head and neck and its results of treatment. Br J Radiol 2005; 78: 1028-1033.
11. Warren S, Gates O. Multiple primary malignant tumours: a survey of the literature and a statistical study. Am J Cancer 1932; 16: 1358-1414.
12. Cahan WG, Woodard HQ, Higinbotham NL et al. Sarcoma arising in irradiated bone. Cancer 1998; 82: 8-34.
13. Oota S, Shibuya H, Hamagaki M et al. Oral pseudotumor. Cancer 2003; 97: 1353-1357.
14. Miyoshi T, Takebayashi S, Suzuki C et al. Early-onset postirradiation sarcoma of the tongue after pseudotumor phase. ORL J Otorhinolaryngol Relat Spec 2011; 73: 201-205.
15. Sakai K, Kitamura T, Hinata H. Second cancers following radiotherapy for malignant tumors the second mail survey in Japan. J Japan Radiol Soc 1986; 46: 811-818 (in Japanese).
Copyright: © 2022 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.