Abstract
Background
Primary soft tissue sarcomas are uncommon. We report a case of primary breast osteosarcoma which was treated successfully. This case report is combined with a literature review of this rare breast malignancy.
Methods
Electronic literature search of databases: Pubmed/Medline, Ovid and EMBASE, in addition to the search engines Google/Google Scholar and Bing. The keywords used were breast osteosarcoma, soft tissue sarcoma and breast cancer. Searches were screened and those studies thought to be relevant had full text versions retrieved. The references to all retrieved texts were searched for further relevant studies.
Conclusion
Primary breast osteosarcoma is a rare breast malignancy that affects elderly patients. Diagnosis is often challenging and can be debatable due to its rarity, non-specific radiological findings and the complicated histopathological subtypes. Surgery is the treatment of choice.
Case report
An 81-year-old Caucasian woman presented to the outpatient breast clinic with a few weeks’ history of a painless lump in her right breast. The lump was steadily increasing in size. She did not have any significant medical history or family history of breast cancer.
Clinical examination revealed a 3 cm × 2 cm palpable lump in the lower inner quadrant of the right breast. There were no overlying skin changes or palpable right axillary lymph nodes. The palpable lump corresponded to a 34-mm irregular dense mass with microcalcification on mammography (Figure 1), and a 27-mm irregular hypoechoeic lesion on ultrasound scan (USS), (Figure 2). The USS showed no enlarged axillary lymph nodes.
Irregular dense mass with microcalcification on right breast mammography. USS of the right breast showing an irregular hypoechoic mass.
Fine-needle aspiration of the palpable lump was then performed; this was reported as C5 (malignant). Nevertheless, the core biopsy was not conclusive, but there was a suspicion of either sarcoma or metaplasia. Due to the uncertainty of the diagnosis, a decision to perform an urgent surgical biopsy was agreed at a multidisciplinary team level. However, the patient was very anxious and worried. After a thorough discussion with the surgical team that covered all the treatment options, the patient chose to have a right mastectomy with axillary node sampling. The patient also had localised post-operative radiotherapy as per the oncologist’s advice.
The standard protocol in our unit at the time of the patient’s presentation was that all the patients who need breast cancer surgery should undergo USS of the axilla. If no enlarged axillary lymph nodes were detected on USS, then the patients used to have axillary lymph nodes sampling, in addition to the breast surgery. The sentinel lymph node biopsy protocol was not fully established in our unit then.
The histopathology report showed that the tumour dimensions were of 30 × 20 × 20 mm. It appeared well circumscribed, relatively uniform with central necrosis. It comprised of osteoid multinucleate giant cells and abundant undifferentiated stroma. There was no evidence of any epithelial component and staining for cytokeratins like 34beta12E and MNF16 were negative. The tumour was also negative for smooth muscle actin. The stromal component was strongly positive for vimentin. There was no vessel space invasion. Excision was complete by a margin of at least 20 mm. There were no features suggesting any antecedent phylloides tumour (Figure 3). The dissected right axillary lymph nodes showed reactive features only, with no evidence of metastatic carcinoma. Overall, the histological features were those of a primary breast osteosarcoma (PBO).
Histology slide showing osteoid multinucleate giant cells and abundant undifferentiated stroma. The stromal component is strongly positive for vimentin.
It has been more than four years since the patient had the mastectomy with no signs of recurrence so far. She is still undergoing regular follow-up.
Discussion and literature review
Epidemiology
Primary breast sarcomas are uncommon and represent less than 1% of all breast malignancies. PBO is rare and represents 12.5% of all mammary sarcomas. Unlike skeletal osteosarcomas, it tends to affect older patients, typically between the sixth and the eighth decades of life.1–6
Pathophysiology
PBO is a high-grade malignant mesenchymal neoplasm that produces neoplastic osteoid, bone and controlled material with no evidence of an epithelial component. The lack of the epithelial element helps in its histological differentiation from the more common epithelial origin bone producing spindle cell neoplasms like metaplastic or sarcomatoid carcinomas. It is characterised by poor prognosis, early recurrences and haematogenous metastasis. The most common sites of metastasis are the lungs (80%), bone (25%) and liver (17%). As it is the case with most adult sarcomas, lymph nodes are not usually involved, even in advanced cases with distant metastases. The process by which PBO arises is unclear. The mesenchymal stem cells of the breast stroma (i.e. de Novo) might play a role in the process of PBO development. Other conditions like malignant transformation of existing breast conditions (e.g. fibroadenoma or phylloides tumour), previous trauma and exposure to radiation, have also been correlated with the development of PBO.1,4,5,7–14
Diagnosis
Patients with PBO generally present with a history of an enlarging painless firm breast lump. However, painful lumps have also been reported. Elevated serum alkaline phosphatase levels have been associated with the tumour activity. This level usually declines following surgical excision, making it a useful follow-up biochemical marker for disease monitoring. On mammograms and ultrasound, PBO usually appears as a well-circumscribed and dense lesion with calcifications. Preoperative diagnosis is usually challenging and sometimes can only be established after surgical resection, keeping in mind that the preoperative mammographic appearance of PBO may be mistaken for fibroadenomas in a significant number of cases. Histologically, PBO has three subtypes: osteoblastic, osteoclastic (giant cell-rich) and fibroblasts subtypes. The fibroblasts subtype has the highest survival outcome. The histological diagnosis of PBO is based on the lack of the epithelial component and the presence of neoplastic osteoid or bone.3,9,12,13,15
It is worth mentioning here that the diagnosis of PBO is considered controversial by some clinicians. This debate has been explored in a recent study in multi-institutional series of malignant matrix-producing breast tumours like osetosarcoma and chondrosarcoma. 16 The authors highlighted this dilemma by questioning the actual existence of these breast tumours, and whether they only represent the end stage of trans-differentiation into osteochondroid types with loss of epithelial component. 16
Treatment
Treatment strategy is based on surgery in the form of total excision with clear resection margins or simple mastectomy. Currently, there are no clear guidelines that determine the choice of the surgical options. Nevertheless, some reports indicate that the local recurrence rate is around 67% with wide local excision of PBO and 11% for those treated with mastectomy. There is no routine role for axillary node dissection/sampling, given that lymph nodes are not usually involved in the disease process. However, we did perform axillary node sampling in our case, since we did not have a confirmed diagnosis of PBO before surgery. As far as we know, there is no available strong evidence that supports the role of adjuvant chemotherapy in increasing the overall survival rates in patients with PBO. The same is true for post-operative local radiotherapy, though the latter could play a role in cases where the surgically resected margins are not clear. In advanced cases, palliative adjuvant therapy and surgery for isolated distant metastases can be considered. Published works report a five-year survival of 38% in patients with PBO, while the overall recurrence rate for an extraskeletal osteosarcomas is variable. Overall, there is no clear role for adjuvant chemoradiotherapy, but factors like the tumour site/size/staging, patients’ preference and fitness, and the clearance of the surgical margins may all play a role in this prospect.8,12,13,17–22
Conclusion
PBO is a rare breast malignancy that affects elderly patients. Diagnosis is often challenging and can be debatable due to its rarity, non-specific radiological findings and the complicated histopathological subtypes. Surgery is the treatment of choice in the form of wide local excision with the aim of achieving clear resected margins or simple mastectomy. However, there is no routine role for axillary lymph node dissection/sampling if the diagnosis of PBO is confirmed preoperatively. The role of adjuvant chemoradiotherpay is not clear with controversy in literature due to the lack of strong evidence. As it is the case with all breast tumours, triple assessment approach with decision making at a multidisciplinary level with consideration of the patient’s preference should always be implemented in the setting of the management strategy.
Footnotes
Declaration of conflicting interests
None declared.
Funding
This manuscript received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.