Case Report
Primary breast osteosarcoma: a case report and review of literature
Scottish Medical Journal 2014, Vol. 59(4) e1–e4 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0036933014551674 scm.sagepub.com
Ahmad Al Samaraee1, Nithia Angamuthu2 and Tarannum Fasih3
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.
Keywords Breast osteosarcoma, soft tissue sarcoma, breast cancer
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. 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. 1
Speciality Registrar in General Surgery, Department of General Surgery, Wansbeck General Hospital, UK 2 SHO in General Surgery, Department of General Surgery, Queen Elizabeth Hospital, UK 3 Consultant Surgeon, Department of General Surgery, Queen Elizabeth Hospital, UK Corresponding author: Ahmad Al Samaraee, Department of General Surgery, Wansbeck General Hospital, Ashington NE36 9JJ, UK. Email: [email protected]
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Figure 1. Irregular dense mass with microcalcification on right breast mammography.
Figure 3. Histology slide showing osteoid multinucleate giant cells and abundant undifferentiated stroma. The stromal component is strongly positive for vimentin.
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). 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 Figure 2. USS of the right breast showing an irregular hypoechoic mass.
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
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
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
Al Samaraee et al.
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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 matrixproducing 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
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. 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.
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
References 1. Singhal V and Cosgrove JM. Osteogenic sarcoma of the breast arising in a cystosarcoma phyllodes: a case report and review of the literature. J Med Case Rep 2011; 5: 293. 2. Kennedy T and Biggart JD. Sarcoma of the breast. Br J Cancer 1967; 21: 635–644. 3. Saber B, Nawal A, Mohamed F, et al. Primary osteosarcoma of the breast: case report. Cases J 2008; 1: 80. 4. Trihia H, Valavanis C, Markidou S, et al. Primary osteogenic sarcoma of the breast: cytomorphologic study of 3 cases with histologic correlation. Acta Cytol 2007; 51: 443–450.
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
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5. Coussy F, Le Scodan R, Guinebretiere JM, et al. Breast mass with intense 99mTc-diphosphonate uptake revealing primary breast osteosarcoma. J Clin Oncol 2011; 29: e428–e430. 6. Huvos AG. Clinicopathologic spectrum of osteogenic sarcoma: recent observations. Pathol Annu 1979; 14: 123–144. 7. Allan CJ and Soule EH. Osteogenic sarcoma of the somatic soft tissues: clinicopathologic study of 26 cases and review of literature. Cancer 1971; 27: 1121–1133. 8. Argus A and Halton L. Case of the season: osteosarcoma of the breast. Semin Roentgenol 2011; 46: 4–6. 9. Bahrami A, Resetkova E, Ro J, et al. Primary osteosarcoma of the breast: report of 2 cases. Arch Pathol Lab Med 2007; 131: 792–795. 10. Kaiser U, Barth P, Duda V, et al. Primary osteosarcoma of the breast. Case report and review of literature. Acta Oncol 1994; 33: 74–76. 11. Middela S, Jones M and Maxwell W. Primary osteosarcoma of the breast—a case report and review of literature. Indian J Surg 2011; 73: 363–365. 12. Silver SA and Tavassoli FA. Primary osteogenic sarcoma of the breast: a clinicopathologic analysis of 50 cases. Am J Surg Pathol 1998; 22: 925–933. 13. Dragoumis D, Bimpa K, Assimaki A, et al. Primary osteogenic sarcoma of the breast. Singapore Med J 2008; 49: e315–e317.
14. Harvey JA. Unusual breast cancers: useful clues to expanding the differential diagnosis. Radiology 2007; 242: 683–694. 15. Badge SA, Gosavi AV, Kulkarni MP, et al. Primary osteosarcoma of the breast. Indian Med Gaz 2012; 249–252. 16. Rakha EA, Tan PH, Shaaban A, et al. Do primary mammary osteosarcoma and chondrosarcoma exist? A review of a large multi-institutional series of malignant matrixproducing breast tumours. Breast 2013; 22: 13–18. 17. Teo T and Wee SB. Clinically ‘benign’ breast lumps: sarcoma in hiding? Case reports and literature review. Ann Acad Med Singapore 2004; 33: 270–274. 18. Brown AL, Holwill SD, Thomas VA, et al. Case report: primary osteosarcoma of the breast: imaging and histological features. Clin Radiol 1998; 53: 920–922. 19. Brustugun OT, Reed W, Poulsen JP, et al. Primary osteosarcoma of the breast. Acta Oncol 2005; 44: 767–770. 20. Hassan S and Adari G. Primary breast osteosarcoma. E Afr Med J 2004; 81: 375–377. 21. Irshad K, Mann BS and Campbell H. Primary osteosarcoma of the breast. Breast 2003; 12: 72–74. 22. Khan S, Griffiths EA, Shah N, et al. Primary osteogenic sarcoma of the breast: a case report. Cases J 2008; 1: 148.
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
Primary breast osteosarcoma: a case report and review of literature
Scottish Medical Journal 2014, Vol. 59(4) e1–e4 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0036933014551674 scm.sagepub.com
Ahmad Al Samaraee1, Nithia Angamuthu2 and Tarannum Fasih3
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.
Keywords Breast osteosarcoma, soft tissue sarcoma, breast cancer
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. 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. 1
Speciality Registrar in General Surgery, Department of General Surgery, Wansbeck General Hospital, UK 2 SHO in General Surgery, Department of General Surgery, Queen Elizabeth Hospital, UK 3 Consultant Surgeon, Department of General Surgery, Queen Elizabeth Hospital, UK Corresponding author: Ahmad Al Samaraee, Department of General Surgery, Wansbeck General Hospital, Ashington NE36 9JJ, UK. Email: [email protected]
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
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Scottish Medical Journal 59(4)
Figure 1. Irregular dense mass with microcalcification on right breast mammography.
Figure 3. Histology slide showing osteoid multinucleate giant cells and abundant undifferentiated stroma. The stromal component is strongly positive for vimentin.
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). 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 Figure 2. USS of the right breast showing an irregular hypoechoic mass.
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
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
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
Al Samaraee et al.
e3
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 matrixproducing 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
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. 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.
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
References 1. Singhal V and Cosgrove JM. Osteogenic sarcoma of the breast arising in a cystosarcoma phyllodes: a case report and review of the literature. J Med Case Rep 2011; 5: 293. 2. Kennedy T and Biggart JD. Sarcoma of the breast. Br J Cancer 1967; 21: 635–644. 3. Saber B, Nawal A, Mohamed F, et al. Primary osteosarcoma of the breast: case report. Cases J 2008; 1: 80. 4. Trihia H, Valavanis C, Markidou S, et al. Primary osteogenic sarcoma of the breast: cytomorphologic study of 3 cases with histologic correlation. Acta Cytol 2007; 51: 443–450.
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
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5. Coussy F, Le Scodan R, Guinebretiere JM, et al. Breast mass with intense 99mTc-diphosphonate uptake revealing primary breast osteosarcoma. J Clin Oncol 2011; 29: e428–e430. 6. Huvos AG. Clinicopathologic spectrum of osteogenic sarcoma: recent observations. Pathol Annu 1979; 14: 123–144. 7. Allan CJ and Soule EH. Osteogenic sarcoma of the somatic soft tissues: clinicopathologic study of 26 cases and review of literature. Cancer 1971; 27: 1121–1133. 8. Argus A and Halton L. Case of the season: osteosarcoma of the breast. Semin Roentgenol 2011; 46: 4–6. 9. Bahrami A, Resetkova E, Ro J, et al. Primary osteosarcoma of the breast: report of 2 cases. Arch Pathol Lab Med 2007; 131: 792–795. 10. Kaiser U, Barth P, Duda V, et al. Primary osteosarcoma of the breast. Case report and review of literature. Acta Oncol 1994; 33: 74–76. 11. Middela S, Jones M and Maxwell W. Primary osteosarcoma of the breast—a case report and review of literature. Indian J Surg 2011; 73: 363–365. 12. Silver SA and Tavassoli FA. Primary osteogenic sarcoma of the breast: a clinicopathologic analysis of 50 cases. Am J Surg Pathol 1998; 22: 925–933. 13. Dragoumis D, Bimpa K, Assimaki A, et al. Primary osteogenic sarcoma of the breast. Singapore Med J 2008; 49: e315–e317.
14. Harvey JA. Unusual breast cancers: useful clues to expanding the differential diagnosis. Radiology 2007; 242: 683–694. 15. Badge SA, Gosavi AV, Kulkarni MP, et al. Primary osteosarcoma of the breast. Indian Med Gaz 2012; 249–252. 16. Rakha EA, Tan PH, Shaaban A, et al. Do primary mammary osteosarcoma and chondrosarcoma exist? A review of a large multi-institutional series of malignant matrixproducing breast tumours. Breast 2013; 22: 13–18. 17. Teo T and Wee SB. Clinically ‘benign’ breast lumps: sarcoma in hiding? Case reports and literature review. Ann Acad Med Singapore 2004; 33: 270–274. 18. Brown AL, Holwill SD, Thomas VA, et al. Case report: primary osteosarcoma of the breast: imaging and histological features. Clin Radiol 1998; 53: 920–922. 19. Brustugun OT, Reed W, Poulsen JP, et al. Primary osteosarcoma of the breast. Acta Oncol 2005; 44: 767–770. 20. Hassan S and Adari G. Primary breast osteosarcoma. E Afr Med J 2004; 81: 375–377. 21. Irshad K, Mann BS and Campbell H. Primary osteosarcoma of the breast. Breast 2003; 12: 72–74. 22. Khan S, Griffiths EA, Shah N, et al. Primary osteogenic sarcoma of the breast: a case report. Cases J 2008; 1: 148.
Downloaded from scm.sagepub.com at University of Manitoba Libraries on June 25, 2015
