Abstract
Osteoblastoma is a rare benign primary bone tumor, which occurs in any part of the skeleton. Extraskeletal osteoblastoma is rather rare. We presented an extremely rare case of extraskeletal osteoblastoma located in the breast. The tumor recurred 7 months later after resection and transformed to aggressive osteoblastoma. The histopathological features, ultrasonic manifestations and ultrasonic differential diagnoses of the primary and recurrent tumors were discussed. The recommended treatment of the tumor is surgical excision. Due to its tendency of recurrence and potential malignant transformation, adequate resection and careful follow up is essential.
Introduction
Osteoblastoma is a rare benign primary bone tumor accounting for 1–3% of all primary bone tumors [1, 2]. It occurs more frequently in males than females at a ratio of approximately 2.5 : 1, with peak incidence in patients between 10 and 20 years of age and a range of 3 to 78 years [3]. It occurs in any part of the skeleton, especially in the vertebral column, the metaphysis and distal diaphysis of the long bones, and the skull and facial bones. Extraskeletal osteoblastoma is defined as osteoblastoma arising from tissues out of the bone. A few cases of extraskeletal osteoblastoma have been reported before.
The image manifestations of the skeletal osteoblastoma are variable. The typical image is a “lytic” zone surrounded by bony condensation, with minimal osteosclerotic reaction peripherally. The tumor rarely invades the soft tissues. To our knowledge, characteristic ultrasonic images features of osteoblastoma have not been mentioned in past literatures. Histological examination shows in the tumor osteoid trabeculae is well formed and elongated. It is rimmed by one or several rows of proliferating osteoblasts. No mitoses and no atypia in the osteoblasts or the stromal cells areobserved.
The conventional treatment of osteoblastoma is complete resection. The long-term recurrence rate is about 10 to 15%. Malignant degeneration is rare [4]. All cases transformed to aggressive osteoblastomas reported to date showed the malignant conversion existed only in recurrent tumors [5]. In this study, we presented a case of breast osteoblastoma and its transformation to aggressive osteoblastoma in situ in recurrence after local excision detected by ultrasound.
Case report
A 65-year-old woman visited our hospital with chief complaint of left breast painless mass, found occasionally 6 months before. The isolate lesion’s diameter was about 3 cm, locating at the superior lateral quadrant of the breast. It was hard, but not fixed. No pain and no nipple discharge were complained. Subsequent ultrasound examination found a round, hypoechoic mass in the gland, with broad and coarse hyperechoic ring. Because of remarkable sound attenuation, only the front part of calcification was visible. It was like part of “egg-shell”. This kind of calcification was quite different. Another remarkable symptom was the hypoecho band around the tumor, which probably suggested the cluster of tumor cells and edema of the soft tissues surrounding the tumor. No blood flow signal was detected (Fig. 1). A benign lesion, such as remote galactostasia with calcification was suspected preoperatively.
Ultrasonic features of the breast osteoblastoma preoperative. (A) A round, hypoechoic mass with coarse hyperechoic calcification and remarkable hypoecho band around, like part of “egg-shell”, (B) Color Doppler flow imaging showing no blood flow signal in the lesion.
The patient received simple resection of the mass. Gross pathological examination revealed that the tumor was well circumscribed by a capsule and very hard to be dissected. The tumor’s diameter was about 2.5 cm. Microscopically, the tumor had clear boundary. It consisted of well formed, elongated osteoid trabeculae rimmed by one or several rows of proliferating osteoblasts. The osteoblasts were small and basophilic. Cellular atypia was absent and none of mitoses were seen (Fig. 2). The histological examination of the material suggested the diagnosis of benign osteoblastoma.
Histopathological findings of the primary tumor by hematoxylin and eosin staining, diagnosed as benign breast osteoblastoma. (A) A well-defined mass with a lobule of mammary gland besides (magnification,×100); (B) Well formed osteoid trabeculae, rimmed by one or several rows of proliferating osteoblasts. No mitoses and no atypia in the osteoblasts or the stromal cells being observed (magnification,×200).
The patient returned our hospital 7 months later, with a palpable mass about 5 cm diameters at the same position of the breast. The mass was hard and was almost fixed to the chest. The partial skin was red. None of enlarged lymph nodes was palpable. Ultrasonic images showed two well-demarcated small lesions with incomplete “egg-shell” calcification in the fat tissue of the breast. Neither lesion was larger than 1 cm in diameter. The grey scale ultrasonic image features were similar to the former findings. However, significant dotted blood flow signals around the tumor were observed by color Doppler flow imaging (Fig. 3). An enlarged axillary lymph node was detected with abnormal thickening cortex. Obviously the mass recurred at the same position.
Ultrasonic features of the recurrent tumor. (A) Two well-demarcated small lesions with incomplete “egg-shell” calcification in subcutaneous tissues; (B) Color Doppler flow imaging showing significant dotted blood flow signal around the tumor.
Another resection was undergone and the pathological findings were different from the former. The mass was firm and ossified. Its margins were ill-defined. Microscopically the stroma was composed of disorganized and dilated osteoid trabaculae, with many more cellular components clustered in it. Epithelial-like osteoblasts had significant hyperplasia. They were arranged in a prominent nesting pattern. The nuclei of the cells were also atypical and had prominent nucleoli. Mitotic figures were not observed. (Fig. 4). These histologic findings were consistent with the diagnosis of aggressive osteoblastoma. Follow-up ultrasound was performed at 3 months intervals; however, no recurrence was observed over a period of 9 months.
Histopathological findings of the recurrent tumor by hematoxylin and eosin staining, diagnosed as progressive breast osteoblastoma. (A) Stroma composed of disorganized and dilated osteoid trabaculae, with many more cellular components clustered (magnification,×100), (B) Atypical epithelial-like osteoblasts with prominent nucleoli, arranged in a prominent nesting pattern(magnification,×400).
Osteoblastoma is a rare and benign primary bone tumor. Extraskeletal osteoblastoma is extremely rare. Few documented cases have been reported in English literature. Agarwala R et al. [6] and Ledeboer QC [7] had reported osteoblastoma of the thyroid cartilage and the cricoid cartilage, in which the tumors assumed to arise in foci of ossified cartilage. Deyrup AT et al reported a case of osteoblastoma arising from axilla [8]. Another fibro-osseous lesion of the pineal region was reported with pathological features similar to osteoblastoma [9]. Our case demonstrated the tumor occurred in the breast, without direct attachment to skeletal system. Its pathogenesis is indistinct. Most researchers consider the pluripotent mesenchymal stem cells can differentiate into osteoblasts forming the tumor. Some researchers assume the tumor may arise from heterotopic ossification [6, 7].
High resolution ultrasound is useful in the diagnosis of mammary disease. But the sonographic manifestations of the breast osteoblastoma have scarcely been described because of the rarity of this disease. The imaging manifestations of the osteoblastoma depend on the various degree of ossification [10–12]. X-ray and CT scans are the most common tools for the diagnosis of skeleton osteoblastoma. On conventional radiography and CT scans images, the characteristic of skeletal osteoblastoma is a “lytic” zone surrounded by bony condensation, with minimal osteosclerotic reaction peripherally. The tumor rarely invades the soft tissues. MRI is more effective than CT and conventional radiography when evaluating the intracranial and intraosseous extension of the tumor. In our case the primary tumor showed a round mass with peripheral “egg-shell” calcification. This “egg-shell” calcification is broad and coarse, and only the front part was visible.
The differential diagnoses of the osteoblastoma in breast in ultrasound include remote galactostasia, fibroadenoma with calcification, calcified breast cancer, and breast osteosarcoma. The breast osteoblastoma manifests a round mass, with distinct margin and wide “calcified ring”. The ultrasound characteristics of remote galactostasia are irregular configuration, distinct margin, bulky and irregular calcifications. The manifestations of typical breast cancer with calcification include irregular configuration, spiculate and foliar margins and grit calcification. Calcified fibroadenoma shows a lesion with regular or lobulated figure. It has different size of blocky calcifications inside. In view of its clear boundary and peripheral soft tissues not involved, a hypothetical diagnosis of breast osteosarcoma should be excluded.
The biologic behavior of the benign osteoblastoma is not consistent. The tumor can transform to aggressive osteoblastoma or even to osteosarcoma, especially in recurrent lesion. Previous study showed rate of local recurrence with curettage was as high as about 16% in skeletal system, attributed to inadequate curettage or partial resection of the tumors [13]. Although the tumor’s margin is well defined on the radiological and ultrasonic images, it is difficult to determine the exact margin during the operation [14]. That might be the cause of its recurrence. Oliveira CR et al indicated proliferating cell nuclear antigen labeling index and p53 may be useful predictors of recurrence [15]. In this case, the recurrent lesion evolved into progressive osteoblastoma, and was almost successfully managed with en bloc resection in a 9-months follow up intervals. But the old woman should need close monitoring continuously because the possibility of recurrence and malignant transformation.