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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 54  |  Issue : 5  |  Page : 191-195

Primary osteosarcoma of the breast


1 Department of Surgery, St. Joseph Hospital, Kaohsiung, Taiwan
2 Union Pathology Center, Kaohsiung, Taiwan

Date of Submission04-Jan-2021
Date of Decision22-Apr-2021
Date of Acceptance10-Jul-2021
Date of Web Publication12-Oct-2021

Correspondence Address:
Hung-An Huang
Department of Surgery, St. Joseph Hospital, Kaohsiung
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_233_20

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  Abstract 


A 58-year-old female with a primary osteosarcoma of the breast (POB) is presented here. The diagnosis was based on the characteristic histological picture and on the immunohistochemical results. The possibility of the secondary lesion from a primary skeletal osteosarcoma or direct extension of an osteogenic sarcoma arising from nearby ribs or the sternum was excluded. Approximately, 150 cases of POB had been reported in the literature with tumor size affecting survival. The diagnosis needs to be made as early as possible to improve the survival of this disease.

Keywords: Extraskeletal osteosarcoma, osteosarcoma, primary breast osteosarcoma


How to cite this article:
Huang HA, Wang SL. Primary osteosarcoma of the breast. Formos J Surg 2021;54:191-5

How to cite this URL:
Huang HA, Wang SL. Primary osteosarcoma of the breast. Formos J Surg [serial online] 2021 [cited 2021 Nov 28];54:191-5. Available from: https://www.e-fjs.org/text.asp?2021/54/5/191/327886




  Introduction Top


Primary osteosarcoma of the breast (POB) is an extremely rare and aggressive neoplasm. In 2008, Khan et al. reported approximately 150 cases of POB in literatures since 1957,[1] whereas Jernstrom et al. observed only one case of osteosarcoma in 3319 cases of mammary carcinoma over a period of 18 years.[2] For over 60 years, 24 out of 25 patients in the Mayo Clinic series had a primary breast sarcoma that presented with a palpable mass, of which one was osteosarcoma.[3] In this regard, almost every reference to this entity in the literature was in the form of a single-case report. The largest collection of POB found in PubMed search from 1967 to date was a clinicopathologic analysis of fifty cases seen over a 38-year period reported by Silver and Tavassoli in 1998.[4]

In our report, we describe a single case of this uncommon tumor.


  Case Report Top


A 58-year-old female was presented to St. Joseph Hospital in June 2020 with a palpable breast mass, of which she said had been palpable for 2 months and had been growing fast. However, she did not feel pain nor had any nipple discharge. A hard and movable mass with well-circumscribed margins about 5 cm was noted upon clinical examination at a 2 o'clock position in the superior-inner quadrant of the right breast. There was no history of breast trauma, radiotherapy, or family history of breast cancer. A large calcification mass was noted in mammography at the central posterior third of the right breast, and benign calcified mass was suspected with a report of BI-RADS Category 3 [Figure 1]a and [Figure 1]b. Breast ultrasound revealed an irregular and well-circumscribed hypoechoic mass with calcification in right breast that measured 5 cm in diameter and with increased blood flow at 2 o'clock. Category 4b in BI-RADS was reported [Figure 2]a and [Figure 2]b. Core-needle biopsy of the mass was performed. Pathology revealed the presence of atypical cells, admixed with osteoid-like tissue, and some multinucleated giant cells. The patient underwent partial mastectomy (complete excision of the tumor with safety margins). During surgery, the mass was not attached to the sternum nor the underlying ribs. Gross examination revealed a well-circumscribed tumor (4 cm × 3.6 cm), which was gray white color and firm to hard in consistency. Microscopically, it showed an infiltrative bone-forming tumor composed of a sheet-like or lace-like osteoid in between neoplastic cells, exhibiting hyperchromatic nuclei, prominent nucleoli, and active mitoses [Figure 3] and [Figure 4]. The neoplastic cells admixed with some multinucleated giant cells resembling osteoclasts were also present [Figure 5]. On immunohistochemistry (IHC), the tumor cells were positive for vimentin and negative for cytokeratin (AE1/AE3) [Figure 6] and [Figure 7]. No carcinomatous nest, nor in situ component, nor leaf-like projection suggestive of phyllodes neoplasm was seen in the tumor. A diagnosis of osteosarcoma of the breast was made, and the resection margins were free. The patient was subsequently referred to a medical center (Kaohsiung Chang Gung Memorial Hospital), where the samples were collected and further reviewed by other pathologists who concurred with the diagnosis of osteosarcoma (Grade 3, osteoblastic type) of the breast. Whole-body scan with Tc-99m methylene-diphosphonate (MDP) was performed and showed negative bony metastasis, whereas computer tomography (CT) staging showed no other distant metastasis. The diagnosis of POB was confirmed. Oncologist took over the patient, and adjuvant chemotherapy was initiated.
Figure 1:

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Figure 2:

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Figure 3: An infiltrative bone-forming tumor composed of sheet-like or lace-like osteoid in between neoplastic cells (H and E, ×100)

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Figure 4: Pleomorphic tumor cells with hyperchromatic nuclei and prominent nucleoli, (H and E, ×400)

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Figure 5: Neoplastic cells admixed with some multinucleated giant cells resembling osteoclasts (H and E, ×200)

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Figure 6: On immunohistochemistry, the tumor cells are positive for vimentin

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Figure 7: On immunohistochemistry, the tumor cells are negative for cytokeratin

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  Discussion Top


POB is a type of extraskeletal osteosarcoma (ESOS), which is a rare malignant mesenchymal tumor characterized by the production of neoplastic osseous tissue with no attachment to bone or periosteum. It predominantly occurs in the lower extremity, upper extremity, and retroperitoneum, but rarely in the visceral organs. ESOS has been reported in other organs such as thyroid, kidney, bladder, colon, heart, testis, penis, gallbladder, and the cerebellum, with the mammary osteosarcoma forming a much smaller group.[5]

In other words, mammary sarcomas are very uncommon and makeup <1% of all primary breast malignancies.[6] The most common breast sarcomas include fibrosarcoma, malignant fibrous histiocytoma, angiosarcoma, and liposarcoma, with POB being extremely rare and representing 12.5% of mammary sarcomas.[6] It is a well-known fact that conventional skeletal osteosarcoma affects mainly young patients, but POB commonly affects older patients with a mean age of around 65 years.[4] One case report occurs in a male patient[4] and one case in a 16-year-old female.[7]

The risk factors have been identified for some ESOS and include prior local irradiation, trauma, and foreign body. Many osteosarcomas of the breast have been described in association with a biphasic tumor.[4] In this regard, most cases with POB develop; however, without a recognized etiologic factor.[8]

The pathogenesis of POB remains unclear, with some reports suggesting the tumor develops from totipotent mesenchymal cells of the breast stroma or from the transformation of a preexisting fibroadenoma or phyllodes tumor.[9]

Most patients with POB present with a palpable, painless, and fast-growing mass which is also firm, mobile, and circumscribed without involving the axilla lymph node nor any nipple retraction.[4]

It is very difficult to diagnose POB by clinical features, mammogram, and ultrasound alone.

The former findings often show large calcified masses, but both POB and involuted fibroadenomas may present popcorn calcification in the breast. This in turn may lead to a delay in the initiation of proper treatment.[7] Digital breast tomography may, in this regard, be helpful in distinguishing the two entities, as osteosarcoma shows a speculated or sunburst margin of calcification rather than the smooth calcified margin that is typically seen with fibroadenomas.

Furthermore, in ultrasound imaging, the tumor may be observed with blurred outlines, heterogeneous echogenicity, and focal calcification.

Bearing in mind, Tc-99m MDP is a specific marker for the osteoid neoplasm. Tc-99m methoxyisobutylisonitrile (MIBI), a radiopharmaceutical agent for myocardial perfusion, has been used in tumor staging. A POB patient with an intense breast uptake of Tc-99m MIBI and Tc-99m MDP is observed on a Tc-99m MIBI scintimammography and whole-body bone scan. In addition, a skeletal scintigraphy with Tc-99m MDP helps to exclude primary skeletal osteosarcoma with breast metastasis.

CT scan plays a very important role in determining the extent of the lesion, to exclude bony origin from underlying bony cage, ribs, or sternum and to exclude any metastasis.

Histopathological evaluation is fundamental for the diagnosis of primary ESOS, which according to the criteria established in the study by Allan and Solle should be as follows: the presence of neoplastic osteoid or bone tumor in the microscopic section, exclusion of origination from the bone, and the absence of an epithelial component.[10] The most frequently observed histologic variants in the POB are fibroblastic, osteoblastic, and osteoclastic (giant cell-rich) variants. Neoplastic cells include spindle elements with features of fibroblasts, polyhedral osteoblasts, and multinucleated osteoclast-like giant elements. The exact diagnosis is based on a failure to detect any epithelial component in the tumor bulk. The presence of osteoid tissue in breast lesions is not an exact diagnostic indicator of breast osteosarcomas and it can occur in both benign and malignant epithelial neoplasms of the breasts such as fibroadenoma, phyllodes tumor, or metaplastic carcinoma. Therefore, the diagnosis of primary breast osteosarcoma can only be made after exclusion of the metaplastic carcinoma or biphasic tumor.[4] Similarly, POB should be separated from two other similar entities, namely, malignant phyllodes tumor and metaplastic carcinoma as they differ completely in terms of both therapeutic and prognostic aspects. The differential can be done by specific morphological and IHC features. IHC, for example, plays an important role in differentiating POB from metaplastic breast carcinomas, the latter being immunopositive to epithelial markers such as cytokeratin, whereas POB is not. The cells from POB are positive for vimentin and negative for estrogen receptor, progesterone receptor, and HER2/neu.

Differential diagnosis includes secondary lesion from a primary skeletal osteosarcoma or direct extension of an osteogenic sarcoma arising from nearby ribs or the sternum. Skeletal scintigraphy with Tc99m-MDP should be used to rule out a primary skeletal osteosarcoma.

Due to rarity of the disease, the optimal treatment strategy for POB is varied.

With most authors concluding that extended wide excision with free margins should be done, some authors report that optimal management should also include mastectomy as a wide excision seems to be complicated by local recurrence,[4] which was 67% for patients treated with a local excision and 11% for those treated with mastectomy.[4] Since axillary lymph nodes involvement is rare, axillary lymph node dissection has not yet been suggested in the literature.

Although adjuvant chemotherapy has dramatically increased the survival of patients with primary skeletal osteosarcoma, the response to POB is still unclear due to limited available data.

The role of postoperative radiotherapy following curative resection is still controversial as conventional osteosarcoma is believed to be relatively resistant to radiation therapy. In cases of positive margin, after surgery or a huge mass that cannot be well excised, radiotherapy may be performed.

The long-term prognosis of mammary osteosarcoma has not been studied in detail, because only a few number of cases have been reported so far. In a study of 50 patients with POS by Silver and Tavasssoli, 5-year survival rate of 38% is reported, with 28% of patients developing local recurrence and 40% developing distant metastasis.[4] They are known for early hematogenesis as opposed to lymphatic spread, most commonly to the lungs and followed by bone and liver. Several factors are found to affect prognosis, such as the size of the tumor, degree of mitoses, presence of stroma atypia, the subtype, and margin status.[4] The size of the tumor is the most important factor. A tumor <4.6 cm in diameter is associated with better survival,[4] whereas the state of surgical margin significantly affects recurrence, local failure, and survival. Patients with a fibroblastic subtype have a significantly better 5-year survival rate (67%) than those with osteosarcoma of the osteoclastic or the osteoblastic subtype (31%).[4]


  Conclusion Top


POB is extremely rare. Diagnosis is based on the characteristic histological picture, immunohistochemical results, and exclusion of the possibility of secondary lesions from a primary skeletal osteosarcoma or direct extension of an osteogenic sarcoma arising from nearby ribs or sternum. The image studies, including mammography and ultrasound, often resemble those of benign lesions. In this regard, tissue diagnosis is mandatory for a large or rapidly growing calcified mass. The optimal treatment is adequate extent of surgery, whereas the role of postoperative chemotherapy or radiotherapy remains unclear. Even though axillary dissection can be spared, the prognosis is generally dismal. However, an early diagnosis may improve the chances of survival.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her image and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Khan S, Griffiths EA, Shah N, Ravi S. Primary osteogenic osteosarcoma of the breast. A case report. Cases J 2008;1:148.  Back to cited text no. 1
    
2.
Jernstrom P, Lindberg AL, Meland ON. Osteogenic sarcoma of the mammary gland. Am J Clin Pathol 1963;40:521-6.  Back to cited text no. 2
    
3.
Adem C, Reynolds C, Ingle JN, Nascimento AG. Primary breast sarcoma: Clinicopathologic series from the Mayo Clinic and review of the literature. Br J Cancer 2004;91:237-41.  Back to cited text no. 3
    
4.
Silver SA, Tavassoli FA. Primary osteogenic sarcoma of the breast: A clinicopathologic analysis of 50 cases. Am J Surg Pathol 1998;22:925-33.  Back to cited text no. 4
    
5.
Khaldi L, Athanasiou ET, Hadjitheofilou CT. Primary mammary osteogenic sarcoma. Histol Histopathol 2007;22:373-7.  Back to cited text no. 5
    
6.
Bahrami A, Resetkova E, Ro JY, Ibañez JD, Ayala AG. Primary osteosarcoma of the breast: report of 2 cases. Arch Pathol Lab Med 2007;131:792-5.  Back to cited text no. 6
    
7.
James JY, Michael O. Primary osteosarcoma of the breast with extensive chondroid matrix in a teenager female patient: The paradoxical diagnosis in breast mastopathy. Int Med Case Rep J 2020;13:11-6.  Back to cited text no. 7
    
8.
Mujtaba B, Nassar SM, Aslam R, Garg N, Madewell JE, Taher A, et al. Primary osteosarcoma of the breast: Pathophysiology and imaging review. Curr Probl Diagn Radiol 2020;49:116-23.  Back to cited text no. 8
    
9.
Yoon CS, Kang SS. Primary osteosarcoma of the breast: A case report. Ann Surg Treat Res 2017;93:57-60.  Back to cited text no. 9
    
10.
Allan CJ, Solle EH. Osteosarcoma of the somatic soft tissue. Clinicopathologic study of 26 cases and review of literature. Cancer 1971;27:1121-33.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]



 

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