Introduction

Adjuvant RT after breast surgery is crucial for patients with breast cancer.  While RIS is a rare complication of RT for breast cancer, RIS after primary breast cancer has a higher incidence compared to other primary solid cancers (1).  Cahan et al. (2) stated the criteria for RIS, with a revision by Arlen et al. (3): 1) the new tumor must occur 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 (an interval of 3 to 4 years) between the two malignancies.  While angiosarcoma in remnant breast is well known as RIS after breast conserving surgery (4, 5), RIS can occur in any other sites than remnant breast in the irradiated field (5-9).  We demonstrated RIS in the soft tissue of lower axilla, which was difficult to distinguish from recurrent lymph node, after total mastectomy with adjuvant RT for breast cancer.

Case report

A 64-year-old woman had undergone right total mastectomy and sentinel lymph nodes biopsy for breast cancer 4 years ago.  While histological diagnosis of primary breast cancer was ductal carcinoma in site (Fig.2-A), tumor size was large (60 x 40 mm) and a negative surgical margin was not assured.  Therefore, she had undergone postoperative adjuvant RT (50 Gy) on right whole chest wall.  Postoperative screening US revealed an oval heterogeneous mass (14 x 12 mm) in the right lower axilla (Fig.1-A) and an abundant vascularity in the mass was detected by color doppler US (Fig.1-B).  Contrast CT revealed enhancing mass (Fig.1-C) and PET also revealed an abnormal radioactive concentration with a maximum standard uptake value of 3.8 (Fig.1-D), while there was no abnormal radioactive concentration in other sites than the right axilla on PET.  Since recurrent lymph node was suspected based on the clinical history and location of the mass, a US-guided FNA was done.  The cytological study demonstrated a small group of large cells with high nuclear-to-cytoplasmic ratio, which had a hyperchromatic nuclei with anisokaryosis and irregular nuclear membrane (Fig.2-B), suggesting a malignant cell.  Core needle biopsy (CNB) could not be done since it was located in close proximity to the chest wall.  Surgical resection, therefore, was performed for definite diagnosis and treatment.  The mass (10 mm in size) was located between the lateral edge of right pectoralis major muscle and right serratus anterior muscle.  Histological study on the tumor revealed a proliferation of polygonal-shaped tumor cells having hyperchromatic and bizarre nuclei arranged in haphazard patterns, accompanied by hyalinized fibro-myxoid stroma, while mitotic figures were occasionally seen (Fig.2-C, D).  Immunohistochemical staining revealed negative expression of ER, PgR, Her2, CAM5.2, AE1/AE3, EMA, desmin, S-100 and focal expression of alpha-SMA, and a Ki-67 proliferative index of 20%.  The histological and immunohistochemical findings were consistent with undifferentiated pleomorphic sarcoma.  The patient is free from local and distant recurrence 3 years after second surgery.

Figure 1: Images of RIS after total mastectomy with adjuvant RT for breast cancer.

A: Postoperative screening US detected an oval heterogenous hypoechoic mass (14 x 12 mm) with irregular margin in the soft tissue of the right lower axilla.  B: Collar doppler US demonstrated an abundant vascularity in the mass.  C: Contrast CT demonstrated the enhancing mass (arrow) in the soft tissue of the right lower axilla, which was close to the right serratus anterior muscle.  D: PET revealed an increased radioactive concentration (arrow) with a maximum standard uptake value of 3.8.

Figure 2: Histological finding of primary breast cancer and cytological and histological findings of RIS.

A: Histological finding on primary breast cancer which was resected 4 years ago demonstrated ductal carcinoma in situ.  B: The cytological study of FNA revealed a small group of large cells with high nuclear-to-cytoplasmic ratio, which had a hyperchromatic nuclei with anisokaryosis and irregular nuclear membrane.  C and D: Histological study on the RIS revealed a proliferation of polygonal-shaped tumor cells having hyperchromatic and bizarre nuclei which were arranged in haphazard patterns and accompanied by hyalinized fibro-myxoid stroma, while mitotic figures were occasionally seen.

Discussion

Angiosarcoma is well known as a histological subtype of RIS which occurs in the remnant breast after breast conserving surgery (4, 5).  On the other hand, other histological subtypes of RIS, such as undifferentiated pleomorphic sarcoma (formerly referred to as malignant fibrous histiocytoma), leiomyosarcoma, fibrosarcoma, osteosarcoma, have been also reported after breast cancer (5-9).  While the remnant breast is the most common site for RIS after breast cancer, RIS occurs in any other sites than remnant breast in the irradiated field (5-10).  The relationship between the sites of RIS and histological subtypes of RIS after breast cancer has been reported (5-8).  Salminen SH et al. (5) demonstrated that the site was a remnant breast in 46 (48%) of 96 RIS after breast cancer and the histological subtype of 37 of these 46 RIS was angiosarcoma.  On the other hand, the histological subtypes of RIS which occurred in other sites than remnant breast was other subtypes than angiosarcoma in 37 of 50 RIS and all 4 RIS which occurred in the axilla was other subtypes than angiosarcoma.  Kirova YM et al. (6) demonstrated the site was a remnant breast in 13 of 27 RIS after breast cancer and the histological subtype was angiosarcoma in 12 of these 13 RIS, while only 1 of 14 RIS which occurred in other sites than remnant breast was angiosarcoma and the histological types of 3 RIS which occurred in the axilla were undifferentiated sarcoma.  Langrange J et al. (8) demonstrated that the histological subtype of 6 of 9 RIS which occurred in the remnant breast was angiosarcoma, while the histological subtype of 3 RIS which occurred in the axilla was malignant fibrous histiocytoma.  Another RIS of malignant fibrous histiocytoma which occurred in the axilla after breast cancer was also reported (9).  These studies demonstrated the inverse relationship between the site of RIS and histological subtypes of RIS, which is that the prevalent histological subtype of RIS which occurs in the remnant breast is angiosarcoma, while the majority of histological subtypes which occur in other sites than remnant breast is other subtypes than angiosarcoma.

Due to the rarity and the diversity of subtypes of soft tissue sarcomas, it is thought to be difficult to diagnose them accurately (4, 10, 11).  Some radiological studies demonstrated the difference between the malignant and benign masses, it is difficult to differentiate sarcoma from carcinoma (10, 11).  In this case, abundant vascularity in the mass on collar doppler US, enhancing mass on CT and abnormal uptake on PET suggested the malignant tumor.  The definite radiological diagnosis, however, of sarcoma from recurrent lymph node was difficult since the size of the mass was small.  The study of comparison of FNA, CNB and surgical biopsy in the diagnosis of soft tissue masses demonstrated that FNA had a 33.3% accuracy and CNB had a 45.6% accuracy in regard to determining exact diagnosis, while open surgical biopsy was 100% accurate (12). In this case, the cytological finding of FNA suggested the malignant tumor, while it was difficult to do CNB due to the location of the mass.  Surgical resection, therefore, was performed for definite diagnosis and treatment.

In conclusion, RIS, which is very rare, should be one of differential diagnosis of recurrent lymph node after mastectomy with adjuvant radiotherapy for breast cancer.

Acknowledgments

We thank Brian Quinn for his review of the manuscript.

Conflict of Interest

The authors declare that they have no competing interests.