Abstract
Mammary carcinoma with osteoclast-like giant cells is an uncommon variant. The following case examines a 36-year-old woman incidentally found to have a left breast mass on routine physical exam. Initial ultrasound-guided core biopsies revealed infiltrating mammary carcinoma with focal mucinous features, for which a left breast lumpectomy and sentinel lymph node biopsy were performed. The sentinel lymph nodes were positive for metastatic mammary carcinoma with osteoclast-like giant cells on permanent section corresponding to the lumpectomy breast specimen, thus a left completion axillary node dissection was subsequently performed.
Introduction
There are a wide variety of breast lesions that on histologic examination may show multinucleated giant cells, one of which is an osteoclast-like giant cell. Mammary carcinomas with osteoclast-like giant cells are extremely rare and have been shown to constitute a small percentage of breast carcinomas. Mammary carcinoma with osteoclast-like giant cells was first described by Rosen in 1979. In a series of 200 consecutive mastectomies They reported finding nine cases (4.5%) of mastectomy specimens.1 Since this initial report, only a few case reports and small case series of mammary carcinoma with osteoclast-like giant cells have been reported. The following case report adds to the growing clinical experience with this atypical variant of mammary carcinoma.
Case Report
The patient is a 36-year-old woman who was incidentally found to have a palpable 2 cm mass in the left breast on routine physical examination. The patient denied any systemic symptoms, weight loss or bone pain and had never noticed or felt the breast mass herself. She has no family history of breast, uterine, or ovarian malignancy.
The patient underwent further evaluation with a diagnostic left breast mammography and ultrasound. These imaging studies documented a 1.9 cm by 1.2 cm hypoechoic mass. Ultrasound guided percutaneous core biopsies were performed, diagnosing invasive mammary carcinoma with focal mucinous features. Preoperative genetic testing was negative for the presence of a BRCA gene mutation.
Following the patient's diagnostic biopsy, she underwent a lumpectomy with sentinel lymph node biopsy. Macroscopic examination of the lumpectomy specimen revealed a well-circumscribed mass that was 1.6 × 1.3 × 1.3 cm in size. Hematoxylin and eosin stained slides revealed an infiltrating mammary carcinoma with osteoclast-like giant cells (Fig. 1). Changes consistent with lymphovascular invasion were identified. Immunohistochemical staining revealed strong estrogen receptor and progesterone receptor reactivity. The carcinoma was also HER 2 and E-Cadherin immunoreactive. Ki-67 was less than weakly positive with a DNA index/ploidy of 1% and S-phase of 2.6. Additionally, three of four sentinel lymph nodes were positive for the presence of metastatic disease on hematoxylin and eosin stained slides.
Figure 1.
Infiltrating ductal carcinoma with osteoclast-like giant cells (arrow). Hematoxylin and eosin stained slide.
Given the presence of metastatic disease by sentinel lymph node biopsy, the patient returned to the operating room for a completion left axillary lymph node dissection. Four additional axillary lymph nodes were identified in the second surgical specimen. In total, two of eight lymphnodes were found to contain metastatic moderately differentiated mammary carcinoma with osteoclast-like giant cells. A third lymph node contained a micrometastasis, less than 2 mm. The final pathologic diagnosis was a Stage IIA (T1cN1M0) moderately differentiated infiltrating mammary carcinoma with osteoclast-like giant cells.
The patient has done well since her breast and axillary surgery, and adjuvant chemotherapy and radiation therapy were well tolerated. She is currently being treated with tamoxifen.
Discussion
Typically osteoclast-like giant cells have been associated with invasive ductal adenocarcinoma of the breast. However, they have also been associated with other histologic types of both malignant and benign breast lesions. These include cribiform, tubular, squamous, papillary, and mucinous breast carcinomas.4,5 Osteoclast-like giant cells have also been reported in infiltrating lobular carcinoma and ductal carcinoma in situ, but their presence is a more rare finding in these two types of carcinoma. In approximately one third of cancers with osteoclast-like giant cells there is axillary node metastasis, leading to a worse prognosis for patients with this form of carcinoma.6
Initial diagnosis of mammary carcinoma is often based on fine needle aspiration or core needle biopsy. Cytologic finding of osteoclast-like giant cells include large cells with abundant cytoplasm and centrally located nuclei ranging in size and number. There are also prominent, associated nucleoli. Diagnosis of osteoclast-like giant cells can be extremely difficult on cytologic exam as these cells can be bland in appearance and have a similar appearance to foreign-body giant cells associated with fat necrosis. As a result, malignant cells may be missed, leading to a false negative diagnosis.5
Microscopic examination of mammary carcinoma cells in the setting of osteoclast-like giant cells often demonstrates hyperchromatic nuclei that are atypical with occasional small nucleoli and fine chromatin structure. Mitotic figures are typically rare.7 There are many other lesions and diseases that may histologically show osteoclast-like giant cells. Examples of such conditions include tuberculosis, sarcoidosis, or granulomatous mastitis. However, in contrast, mammary carcinoma has no histologic characteristics consistent with granulomatous disease.5
The mechanism for development of osteoclast-like giant cells is unknown. However, a current hypothesis states that the cancer cells secrete vasoendothelial growth factor, which promotes angiogenesis and macrophage migration to the neoplasm. Eventually, stromal cells of monocyte origin fuse with each other to become osteoclast-like giant cells.2
In a single institution study utilizing immunohistochemistry to analyze for p53 gene mutations within the carcinoma, the intraductal components had a high expression of p53 with a single point mutation whereas the osteoclast-like giant cells had no expression of p53. This proposes another theory that the osteoclast-like cells are of a different origin than the carcinoma and are possibly a reactive infiltrate.3,8 To date, no formal studies have been performed to correlate prognosis with the presence of osteoclast-like giant cells. There have only been a few reports that have described a less favorable outcome for patients with carcinoma with osteoclastic-like giant cells when compared to other types of mammary carcinoma.3,6
Further research is needed into this atypical variant of breast cancer to better understand its underlying mechanism of development and its effects on tumor biology.
Footnotes
The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government.
References
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