A Radiation Induced Low-Grade Myofibroblastic Sarcoma in the Retropectoral Area After Breast Conserving Surgery: A Case Report

Abstract

Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.

INTRODUCTION

Myofibroblastic sarcoma (MFS) is a rare malignant tumor in which most cells exhibit myofibroblastic features [1]. In 2002, the World Health Organization (WHO) accepted MFS as a distinct subtype of neoplasm [2]. MFS usually develops in the limbs, head, neck, oral cavity, and tongue. Furthermore, it has low potential for tumor recurrence and metastasis [1].

The therapeutic dose of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) can induce chest wall sarcomas, and this is well-documented. However, RT-induced mammary MFS after adjuvant RT for breast cancer has been reported only once [3]. We report another rare case of RT-induced low-grade myofibroblastic sarcoma (LGMFS), which occurred in the retropectoral area. This occurred in a patient who underwent BCS and adjuvant RT for invasive ductal carcinoma (IDC) 16 years previously. Ultimately, this paper details the clinical and radiological characteristics of this case, and provides information about RT-induced low-grade MFS after adjuvant RT for breast cancer.

CASE REPORT

A 49-year-old woman visited our clinic with a suspicious mass observed on postoperative screening ultrasound (US) during follow-up. She had a history of right BCS with adjuvant RT (60 Gy, 30 fractions) and had undergone chemotherapy for IDC 16 years ago. The initial pathological stage of tumor was T2N0M0. Physical examination at our clinic revealed no palpable lesions in either breast, and the laboratory test results were unremarkable.

Breast mammography (MMG, 3Dimensions; Hologic, Marlborough, USA) revealed only post-BCS changes in the upper outer quadrant of the right breast in the craniocaudal and mediolateral oblique views. Breast US (EPIQ; Phillips, Best, Netherlands) demonstrated an oval heterogeneous mass measuring 30 mm in the right retropectoral area (Figure 1A). Moreover, color Doppler US revealed a vessel at the rim of the mass (Figure 1B). Breast magnetic resonance imaging (MRI, Skyra; Siemens, Erlangen, Germany) was performed to further evaluate the mass. T2-weighted imaging (T2WI) revealed a heterogeneous high signal intensity (Figure 1C), and dynamic contrast-enhanced first phase of T1 subtraction imaging revealed a heterogeneous enhancing irregular mass in the right retropectoral area (Figure 1D). Diffusion restriction was observed on diffusion-weighted imaging (DWI) (Figure 1E). An abnormal radioactive concentration was revealed on positron emission tomography-computed tomography (PET-CT), with a maximum standard uptake value (SUV_max) of 8.1 (Figure 1F).

Figure 1. Preoperative images of the radiation induced low-grade myofibroblastic sarcoma.

(A, B) Ultrasound of the right breast shows a heterogeneous ovoid mass at the right retropectoral area with a vessel at the rim. (C) On T2-weighted imaging of the breast, magnetic resonance imaging shows a heterogeneous high signal intensity mass at the right retropectoral area. (D) Dynamic contrast-enhanced first phase of T1 subtraction imaging reveals an irregular mass with heterogeneous enhancement. (E) Diffusion restriction on diffusion-weighted imaging. (F) On positron emission tomography-computed tomography image, an increased radioactive concentration was observed, with a maximum standard uptake value of 8.1.

Based on the clinical history and location of the lesion, the primary differential diagnosis was a metastatic lymph node with atypical imaging features. Therefore, we performed a US-guided core needle biopsy using a 14-gauge BARD Monopty device (BARD, Franklin Lakes, USA) to distinguish between lymph node metastasis and other unexpected tumors. Biopsy revealed a spindle cell tumor with uncertain malignant potential and mild atypia. Surgical resection with a reconstructive latissimus dorsi flap was performed for definite diagnosis and therapy. The size of the tumor was 3.0 × 2.5 cm with a mitotic count of 5/10 high-power fields (HPFs). Immunohistochemical staining revealed positivity for vimentin and smooth muscle actin (SMA), with a Ki-67 proliferative index of 43.1%. The mass was diagnosed as LGMFS (Figure 2). There was a high degree of suspicion of tumor invasion of the resected margins; therefore, after excision of the mass, the patient received adjuvant RT (66 Gy, 33 fractions).

Figure 2. Pathologic findings of the radiation induced low-grade myofibroblastic sarcoma.

(A) Photomicrography of the surgical specimen shows diffuse infiltration growth, with arrangements of cellular fascicles or storiform pattern (H&E, ×40). (B) Photomicrography shows diffuse infiltrative growth of smooth muscle actin-positive spindle cells. (C) Photomicrography shows moderate nuclear atypia, at least focally present (H&E, ×200). (D) The neoplastic cells have pale eosinophilic cytoplasm and elongated fusiform nuclei with evenly distributed chromatin. Increased proliferative activity, was demonstrated as mitoses (arrows) and hyperchromatic nuclei (H&E, ×200).

H&E = hematoxylin and eosin.

DISCUSSION

RT is crucial for patients with breast cancer who undergo BCS; however, short- and long-term complications such as radiation-induced sarcoma (RIS) have been reported. Cahan et al. [4] stated the criteria for RIS which have been revised by several investigators [5,6]: 1) the new tumor must have occurred in a previous RT site; 2) the new tumor must be histologically different from the original tumor; 3) the new tumor should not be present at the beginning of RT; 4) there must be a prolonged period of latency (> 4 years) between the two malignancies. The two most common subtypes of RIS are angiosarcoma and undifferentiated pleomorphic sarcoma, and to the best of our knowledge, only one case of RT-induced MFS has been reported [6].

MFS is an uncommon type of malignant myofibroblastic tumor [1]. MFS was first reported by Wargotz et al. [7] in 1987. It is an atypical tumor composed of spindle-shaped myofibroblasts present in all soft tissue [1]. The WHO categorized this disease entity in the “Pathology and Genetics of Tumors of Soft Tissue and Bone” in 2002 and maintained its classification in 2013 [8]. According the histopathological grading, MFS is divided into low- and intermediate-to-high-grade MFS types, which differ in terms of tumor size, mitotic counts, and proliferative index [8]. The diagnostic criterion for low-grade MFS is less than moderate nuclear atypia with a mitotic cell count ranging between one and six figures per 10 HPF. Our case showed mild nuclear atypia and a mitotic count of five, thus it was diagnosed as low-grade MFS.

In a recent study in the USA, approximately 49 cases of LGMFS were reported. The tumors in this report were commonly found in the extremities (40.8%) and head and neck regions (26.5%) [9]. Lesions with myofibroblastic features can be subdivided into four groups: 1) reactive fasciitis-like lesions, 2) benign myofibroblastic tumors, 3) locally aggressive fibromatosis, and 4) myofibroblastic sarcomas [10].

In imaging studies, there are no pathognomonic features, however these tumors usually appear as well-defined oval heterogeneous echoic masses on US. MRI demonstrates iso or hypersignal intensity on T1-weighted imaging and variable hypersignal intensity on T2WI. Homogeneous enhancement has been observed in contrast enhancement studies, with occasional rim enhancement [1].

There are several differential diagnoses for incidentally detected retropectoral or interpectoral masses, including lymph node metastasis from carcinoma, neurogenic tumors, and soft tissue sarcoma [11]. Among soft tissue sarcomas, angiosarcoma is the most common histological subtype, followed by undifferentiated pleomorphic sarcoma (28%), osteosarcoma (5%), fibrosarcoma (3%), leiomyosarcoma (2%), myxofibrosarcoma (2%), and neurofibrosarcoma (1%) [12]. Angiosarcoma usually shows specific MR imaging features, such as markedly high signal intensity on T2WI due to the vasculature [13]. Undifferentiated pleomorphic sarcomas usually present as well-defined oval masses with heterogeneous signal intensities due to internal hemorrhage, necrosis, and myxoid materials. Identifying the nerve from which the tumor originates can be helpful in differentiating neurogenic tumors. From a histopathological perspective, fibrosarcoma may exhibit focal myofibroblastic differentiation; however, it is typically characterized by high-grade cellular atypia and a distinct herringbone-like fascicular pattern. In contrast, leiomyosarcoma, manifests with a prominent fascicular pattern, a characteristic feature of smooth muscle tumors, and is also marked by abundant eosinophilic cytoplasm. Immunohistochemical studies have shown that leiomyosarcoma is strongly positive for myogenic markers such as SMA, calponin, caldesmon, and desmin, which can aid in its differential diagnosis.

Due to the scarcity of imaging studies on LGMFS, it is difficult to understand the characteristic imaging features of this disease. Therefore, to differentiate these tumors, pathological confirmation through needle biopsy or surgical excision is more appropriate than aspiration. In our case, we decided to perform an US-guided core needle biopsy instead of aspiration because the imaging features were unusual for metastatic lymph nodes. However, it is difficult to diagnose LGMFS using core needle biopsy alone because there are various spindle cell neoplasms showing smooth muscle or myofibroblastic differentiation. Therefore, surgical resection is required for an accurate diagnosis.

Owing to the rarity of this disease entity, no consensus guidelines regarding a standard treatment protocol have been established. However, surgical resection with margins of > 2 cm is recommended. The role of chemotherapy (e.g., apatinib) and RT remains uncertain, and further clinical studies are needed in this regard [14].

Therefore, a comprehensive understanding of LGMFS would benefit clinicians, radiologists, and pathologists in the differential diagnosis of suspected oval masses at previous RT sites.