(Radiographics. 2002;22:691-695.)
© RSNA, 2002
Best Cases from the AFIP
Invasive Ductal Carcinoma with Osteoclast-like Giant Cells1
Riwa Kishimoto, MD,
Yoshiaki Watanabe, MD and
Michio Shimizu, MD2
1 From the Department of Radiology, Hokkaido University Graduate School of Medicine (R.K., Y.W.), and the Department of Surgical Pathology, Hokkaido University Hospital (M.S.), Sapporo, Japan. Received November 27, 2001; revision requested January 8, 2002 and received February 5; accepted February 6. Address correspondence to R.K., Clinical Diagnosis Section, Hospital, National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba 263-0024, Japan (e-mail: riwa@aqua.dti2.ne.jp).
Index Terms: Breast neoplasms, 00.329 • Breast neoplasms, MR, 00.1214 • Breast neoplasms, radiography, 00.11
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History
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A 46-year-old Asian woman who was otherwise healthy presented with a palpable mass in the medial aspect of the right breast. At physical examination, the mass was firm and clearly defined with an irregular surface. Axillary lymph nodes were not clinically suspicious for metastasis. The patient had no significant personal or family medical history. Aspiration biopsy was performed and revealed atypical cells in addition to osteoclast-like giant cells. Although the patient underwent chemotherapy with epirubicin and cyclophosphamide prior to surgery, the size of the tumor did not change.
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Imaging Findings
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Mediolateral oblique and craniocaudal mammography of the right breast demonstrated a round, circumscribed mass in the lower inner quadrant (Fig 1a, Fig 1b), a finding that corresponded to the palpable mass. At close-up mammography, the mass was seen to contain inhomogeneous, scattered high-density areas that appeared to be coarse and fine linear and granular pleomorphic calcifications (Fig 1c). No previous mammograms were available for comparison.
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Figure 1a. (a, b) Mediolateral oblique (a) and craniocaudal (b) mammograms of the right breast demonstrate a round, circumscribed mass in the lower inner quadrant. (c) Close-up mammogram shows the mass with inhomogeneous, scattered high-density areas.
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Figure 1b. (a, b) Mediolateral oblique (a) and craniocaudal (b) mammograms of the right breast demonstrate a round, circumscribed mass in the lower inner quadrant. (c) Close-up mammogram shows the mass with inhomogeneous, scattered high-density areas.
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Figure 1c. (a, b) Mediolateral oblique (a) and craniocaudal (b) mammograms of the right breast demonstrate a round, circumscribed mass in the lower inner quadrant. (c) Close-up mammogram shows the mass with inhomogeneous, scattered high-density areas.
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Magnetic resonance (MR) imaging was performed to evaluate the mass. Axial T1-weighted imaging showed a mass that had lower signal intensity than the surrounding breast tissue and contained several scattered foci of low signal intensity (Fig 2a). At axial T2-weighted imaging, the mass demonstrated extremely low signal intensity (Fig 2b). Dynamic imaging performed with intravenous administration of 0.1 mmol/kg of body weight of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) demonstrated linear patterns of early enhancement centrally within the mass (Fig 2c). At contrast material–enhanced fat-suppressed MR imaging, the mass demonstrated low signal intensity and was surrounded by well-enhanced breast tissue (Fig 2d).
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Figure 2a. (a) Axial T1-weighted MR image (repetition time msec/echo time msec = 600/12) shows a mass with lower signal intensity than the surrounding breast tissue. The mass contains several scattered low-signal-intensity foci (arrows). (b) Axial T2-weighted MR image (4,200/96) shows the mass with extremely low signal intensity. (c) Dynamic images obtained with gadopentetate dimeglumine (4.8/1.65; 15° flip angle, 25-second interval) demonstrate linear patterns of early enhancement centrally within the mass (arrows). (d) Contrast-enhanced fat-suppressed MR image (826/12) shows the low-signal-intensity mass surrounded by well-enhanced breast tissue.
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Figure 2b. (a) Axial T1-weighted MR image (repetition time msec/echo time msec = 600/12) shows a mass with lower signal intensity than the surrounding breast tissue. The mass contains several scattered low-signal-intensity foci (arrows). (b) Axial T2-weighted MR image (4,200/96) shows the mass with extremely low signal intensity. (c) Dynamic images obtained with gadopentetate dimeglumine (4.8/1.65; 15° flip angle, 25-second interval) demonstrate linear patterns of early enhancement centrally within the mass (arrows). (d) Contrast-enhanced fat-suppressed MR image (826/12) shows the low-signal-intensity mass surrounded by well-enhanced breast tissue.
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Figure 2c. (a) Axial T1-weighted MR image (repetition time msec/echo time msec = 600/12) shows a mass with lower signal intensity than the surrounding breast tissue. The mass contains several scattered low-signal-intensity foci (arrows). (b) Axial T2-weighted MR image (4,200/96) shows the mass with extremely low signal intensity. (c) Dynamic images obtained with gadopentetate dimeglumine (4.8/1.65; 15° flip angle, 25-second interval) demonstrate linear patterns of early enhancement centrally within the mass (arrows). (d) Contrast-enhanced fat-suppressed MR image (826/12) shows the low-signal-intensity mass surrounded by well-enhanced breast tissue.
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Figure 2d. (a) Axial T1-weighted MR image (repetition time msec/echo time msec = 600/12) shows a mass with lower signal intensity than the surrounding breast tissue. The mass contains several scattered low-signal-intensity foci (arrows). (b) Axial T2-weighted MR image (4,200/96) shows the mass with extremely low signal intensity. (c) Dynamic images obtained with gadopentetate dimeglumine (4.8/1.65; 15° flip angle, 25-second interval) demonstrate linear patterns of early enhancement centrally within the mass (arrows). (d) Contrast-enhanced fat-suppressed MR image (826/12) shows the low-signal-intensity mass surrounded by well-enhanced breast tissue.
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Pathologic Evaluation
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The patient underwent mastectomy, with resection of axillary and parasternal lymph nodes.
At gross pathologic examination, the tumor was red-brown from old hemorrhage, elastic, soft, and well circumscribed with a capsule. The tumor was 30 x 24 x 22 mm in size.
At histologic analysis, the tumor was relatively well circumscribed with a fibrous capsule and consisted of branching nests of tumor cells enclosing septum-like wide fibrous stroma. Massive hemorrhages of different ages were striking (Fig 3a). Compact tubular growth of tumor cells was observed, along with focal regions of massive extravasation of red blood cells and extensive hemosiderin accumulation in highly vascularized fibrous stroma (Fig 3b). Numerous multinucleated giant cells were scattered in the stroma and were also found in the tubular structures. Diffuse infil-tration by hemosiderin-laden macrophages was seen in the fibrous stroma and also in tumor nests (Fig 3c). No calcifications were present. Intraductal spread was minimal. Neither vascular nor lymphatic invasion was seen, and none of the lymph nodes demonstrated metastasis.
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Figure 3a. (a) Photomicrograph of the sectioned whole mounted specimen (original magnification, x1; hematoxylin-eosin [H-E] stain) demonstrates a well-circumscribed mass consisting of branching nests of tumor cells and fibrous stroma. Massive hemorrhages of different ages within the tumor are striking. (b) Photomicrograph (original magnification, x200; H-E stain) shows tubular growth of the tumor cells and highly vascularized fibrous stroma with extensive hemosiderin accumulation. (c) Higher-power photomicrograph (original magnification, x400; H-E stain) shows multinucleated giant cells scattered both in the stroma and in intraductal spaces (arrows). Diffuse infiltration by hemosiderin-laden macrophages (arrowheads) is remarkable.
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Figure 3b. (a) Photomicrograph of the sectioned whole mounted specimen (original magnification, x1; hematoxylin-eosin [H-E] stain) demonstrates a well-circumscribed mass consisting of branching nests of tumor cells and fibrous stroma. Massive hemorrhages of different ages within the tumor are striking. (b) Photomicrograph (original magnification, x200; H-E stain) shows tubular growth of the tumor cells and highly vascularized fibrous stroma with extensive hemosiderin accumulation. (c) Higher-power photomicrograph (original magnification, x400; H-E stain) shows multinucleated giant cells scattered both in the stroma and in intraductal spaces (arrows). Diffuse infiltration by hemosiderin-laden macrophages (arrowheads) is remarkable.
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Figure 3c. (a) Photomicrograph of the sectioned whole mounted specimen (original magnification, x1; hematoxylin-eosin [H-E] stain) demonstrates a well-circumscribed mass consisting of branching nests of tumor cells and fibrous stroma. Massive hemorrhages of different ages within the tumor are striking. (b) Photomicrograph (original magnification, x200; H-E stain) shows tubular growth of the tumor cells and highly vascularized fibrous stroma with extensive hemosiderin accumulation. (c) Higher-power photomicrograph (original magnification, x400; H-E stain) shows multinucleated giant cells scattered both in the stroma and in intraductal spaces (arrows). Diffuse infiltration by hemosiderin-laden macrophages (arrowheads) is remarkable.
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Discussion
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Carcinomas containing osteoclast-like giant cells have been reported in the breast (1–8), thyroid gland (9), lung (10), pancreas (11), liver (12), gallbladder (13), and kidney (14). Multinucleated giant cells can be found in both benign and malignant entities of the breast, such as benign soft-tissue giant cell tumor, atypical fibrous histiocytoma, sarcoma, metaplastic carcinoma, carcinomas containing malignant epithelial giant cells, and carcinomas with osteoclast-like giant cells (6). Less than 100 cases of breast carcinoma with osteoclast-like giant cells have been reported (1). This entity comprised 0.5%–1.2% of breast carcinomas in two studies (2,3). Most infiltrating breast carcinoma with osteoclast-like giant cells is invasive ductal carcinoma (1,4,5). Less common subtypes include squamous cell carcinoma (7), mucinous carcinoma (4), tubular carcinoma (1), papillary carcinoma (1), invasive cribriform carcinoma (2), adenoid cystic carcinoma (2), and infiltrating lobular carcinoma (5,6).
The clinical features of breast carcinoma with osteoclast-like giant cells are similar to those of breast carcinoma in general. Patients usually present with a palpable breast mass. The average age of patients is about 50 years (1). Some articles suggest a relatively young age for patients at diagnosis (2,3). The lesion has been found in all quadrants (1).
A well-circumscribed dark brown or red-brown tumor is the characteristic finding at gross pathologic examination. The differential diagnosis for this finding in the breast is heavily pigmented metastatic melanoma (1,2). Notable histologic features, both in this case and in other reported cases of breast carcinoma with osteoclast-like giant cells, include increased stromal vascularity, red blood cell extravasation, hemosiderin-laden macrophages, and hemorrhagic foci (1,2,4,6).
Few published studies have mentioned the mammographic appearance of breast carcinoma with osteoclast-like giant cells. Findings of 10 preoperative mammographic lesions in 11 cases have been described in two published reports (2,8). Five of the 10 lesions in these studies were well-circumscribed round tumors, three demon-strated architectural distortion or inhomogeneous density, and two were tumors with marginal spicules. The tumors with well-circumscribed margins were preoperatively interpreted as either a benign lesion (eg, cyst, fibroadenoma) or, occasionally, a malignant lesion (eg, medullary carcinoma) (2). Benign mammographic appearances sometimes cause delay in the treatment of breast carcinoma with osteoclast-like giant cells (2).
In this case, scattered high-density areas within the tumor at mammography were interpreted as calcifications preoperatively. On the basis of radiologic-pathologic correlation, fibrous stroma with extensive accumulation of hemosiderin was suspected to cause these high-density mammographic areas as well as the low-signal-intensity foci at MR imaging. Some metallic substances simulate microcalcifications at mammography. These substances include the dark pigment used in tattooing, which contains iron oxide, and gold deposits in patients with rheumatoid arthritis who have undergone gold therapy (15,16). Because the accumulation of hemosiderin was considerable in this case, it can be presumed that the ferrous element in hemosiderin caused the high-density areas mimicking calcification. To our knowledge, however, no previous reports have described these findings at mammography.
Again, to our knowledge, MR imaging findings in breast carcinoma with osteoclast-like giant cells have not been reported. Old hemorrhage with abundant hemosiderin deposition can cause low-signal-intensity areas with all sequences. Highly vascularized fibrous stroma is thought to cause early enhancement at dynamic imaging because a high correlation between the microvascular density of the tumor and early enhancement has been reported (17).
High-density areas within the tumor at mammography and extremely low-signal-intensity areas within the tumor at MR imaging are thought to reflect the pathologic features of breast carcinoma with osteoclast-like giant cells containing abundant hemosiderin deposition. However, it is unsure how these findings are characteristic for this neoplasm because of the paucity of published articles describing its mammographic and MR imaging appearances.
Primary treatment has usually consisted of mastectomy with axillary dissection (1). The prognosis for this tumor is no more favorable than that for the more typical types of invasive breast cancer (2,5).
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Acknowledgments
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We gratefully thank A. Tsukahara, MD, and R. Yamazaki, RT, Department of Radiology, Hokkaido University Hospital, Sapporo, Japan for preparation of the figures.
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Footnotes
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Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing two beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. Beginning with the July 2001 issue of RadioGraphics, one of these cases is published with each issue of the Journal, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
Abbreviations: H-E = hematoxylin-eosin
2 Current address:Department of Pathology, Saitama Medical School, Saitama, Japan. 
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References
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Hood DL, Bauer TW, Leibel SA, McMahon JT. Hepatic giant cell carcinoma: an ultrastructural and immunohistochemical study. Am J Clin Pathol 1990; 93:111-116.[Medline]
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Grosso LE, Gonzalez JG. Stromal osteoclast-like giant cells in an adenosquamous carcinoma of the gallbladder. Hum Pathol 1992; 23:703-706.[CrossRef][Medline]
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Jackson VP, Jahan R, Fu YS. Benign breast lesions. In: Bassett LW, eds. Diagnosis of diseases of the breast. Philadelphia, Pa: Saunders, 1997; 357-444.
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Wagle WA. Tattoo-induced skin burn during MR imaging. AJR Am J Roentgenol 2000; 174:1795.[Free Full Text]
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Buadu LD, Murakami J, Murayama S, et al. Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis. Radiology 1996; 200:639-649.[Abstract/Free Full Text]
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History
Imaging Findings
