Original Report. Metaplastic Carcinoma of the Breast: Clinical, Mammographic, and Sonographic Findings with Histopathologic Correlation

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1 Isil Günhan-ilgen 1 ysenur Memis 1 Esin Emin Üstün 1 Osman Zekioglu 2 Necmettin Özdemir 2 Received July 30, 2001; accepted after revision December 6, Department of Radiology, Ege Üniversity Hospital, ornova, Izmir, Turkey. ddress correspondence to I. Günhan-ilgen. 2 Department of Pathology, Ege Üniversity Hospital, Izmir, Turkey. JR 2002;178: X/02/ merican Roentgen Ray Society Original Report Metaplastic Carcinoma of the reast: Clinical, Mammographic, and Sonographic Findings with Histopathologic Correlation OJECTIVE. The purpose of this study was to investigate the mammographic and sonographic findings of metaplastic carcinoma of the breast and to correlate the radiologic features with clinical and histopathologic findings. CONCLUSION. Metaplastic carcinoma of the breast often manifests as a rapidly growing, palpable mass that has high density on mammography and may be microlobulated on sonography. Complex echogenicity with solid and cystic components may be seen sonographically and is related to necrosis and cystic degeneration found histopathologically. lthough it is a rare breast malignancy and these features are not unique, metaplastic carcinoma should be included in the differential diagnosis for breast masses with these imaging features. M ost benign and malignant tumors of the breast arise from glandular epithelium. However, in some cases, glandular epithelium differentiates into nonglandular mesenchymal tissue, a process called metaplasia [1]. Metaplastic changes, including squamous cell, spindle cell, and heterologous mesenchymal growth, occurs in fewer than 5% of breast carcinomas [2 6]. Carcinosarcomas, a subgroup of metaplastic carcinomas, are the rarest primary malignancies of the breast (found in < 0.1% of cases) [7]. The differential diagnosis is important for the purposes of treatment and prognosis [1, 4]. lthough the pathologic and clinical aspects of these rare tumors have been described in various reports, to our knowledge, only a few reports, mostly case studies, have been published on the mammographic features [1, 8 13] and sonographic findings [10, 13]. The purpose of this study was to investigate the mammographic and sonographic findings of metaplastic carcinoma of the breast and to correlate the radiologic features with clinical and histopathologic findings. Materials and Methods retrospective review of the mammograms of 1845 histopathologically proven breast cancer cases diagnosed in our mammography unit during the last 15 years revealed eight cases of histopathologically proven metaplastic carcinoma. The history, physical examination, and radiologic (mammographic and sonographic) findings were analyzed in all patients. Patients ranged in age from 44 to 63 years old (mean, 53.8 years). Mammography with two routine positions (craniocaudal and mediolateral oblique) was performed in all the patients using a Senographe Senix 600T (General Electric CGR, Issy Les Moulineaux, France) or a Mammomat 3000 (Siemens, Solna, Sweden) system. ll mammograms were retrospectively reviewed by two radiologists who were specialists in breast imaging. The evaluation was performed as consensus interpretations. Mammograms were evaluated with radiologists unaware of the information from the physical examination or sonography records but aware of the histopathologic diagnosis. Each mammographic lesion was characterized according to size, mass characteristics (shape, margins, density, size, and location), presence and type of microcalcifications, associated architectural distortion, and skin changes. Pa- JR:178, June

2 Günhan-ilgen et al. renchymal patterns were categorized as fatty, scattered fibroglandular tissue, heterogeneously dense, and extremely dense using the merican College of Radiology s reast Imaging Reporting and Data System (I-RDS) [14]. Sonography was performed in all the patients using a 7.5-mHz transducer (SL 70; Toshiba, Tokyo, Japan) or a broadband 5- to 11-MHz transducer (HDL 1000; dvanced Technology Laboratories, othell, W). The sonographic prints and records of each patient were reviewed after the mammograms, in the same evaluation session. Sonograms were assessed for lesion shape, margin, and echogenicity. In the retrospective study, information about preoperative needle biopsies was available in one patient. ll lesions were surgically excised. Microscopic slides of samples of all patients were reviewed by two pathologists who were breast pathology specialists. Each case was reviewed by the two pathologists as a consensus evaluation. The specific metaplastic components were identified. Mammographic and sonographic findings were then correlated with histopathology. Pathologic size, predominant pathologic findings, and lymph node status were obtained from the surgical pathology reports. Results ll eight patients were women, aged years old (mean age, 53.8 years). Only one patient had a risk factor for breast cancer (her sister died of breast cancer at 46 years). In all eight patients referred to our mammography unit for the first time, the presenting complaint was palpable breast mass, and in two of the patients, a rapid growth was noted by the patients. Only one patient had associated bloody nipple discharge, and one patient had a palpable axillary mass. None of the patients had screening mammograms. t physical examination, the size of the masses ranged between 1.5 and 5 cm (mean, 2.6 cm). In two patients, the mass was mobile. In one patient, a dilated superficial vein was noted on the skin near the medial contour of the mass. On the mammograms, in relation to the parenchymal pattern, four breasts were fatty, and four were heterogenously dense. ll eight patients had masses without associated microcalcifications or architectural distortion. In three patients, the margins of the mass were partially obscured by the surrounding breast parenchyma (Fig. 1). The margins of the masses were well circumscribed in two patients and microlobulated (Figs. 2, 3, and 3) in three patients. None of the masses showed prominent spiculations. ll masses were highly dense, and the shape was round in six patients and oval in two. The size varied between 1.5 and 4.5 cm (mean, 2.6 cm). Unfortunately, prior mammograms were not available in any of the patients, so the rapid growth that was noted by the patient could not be confirmed radiologically. The location of the masses were upper outer quadrant in five patients, upper central quadrant in one, lower central quadrant in one, and lower inner quadrant in one. In one patient, the neighboring skin showed focal thickening. On sonographic examination, two masses had discrete well-circumscribed oval contours, whereas six masses showed microlobulation (Figs. 2 and 3C). In one patient, the mass showed heterogenous echogenicity. The mass had both solid and cystic areas (Fig. 1). Fig year-old woman with a rapidly growing 5-cm palpable left breast mass and bloody nipple discharge., Craniocaudal mammogram shows 4.5-cm high-density mass in left inner hemisphere. Posterior margin (small arrow ) of mass is ill-defined, whereas anterior margin (large arrow ) is obscured by fibroglandular tissue and cannot be defined., Transverse sonogram shows mass with irregular margins and heterogenous echogenicity. Mass has both solid (small arrow ) and cystic (large arrow ) components. In another patient, the mass was round, homogeneous, and solid with smooth margins. lthough the mammographic and sonographic features were consistent with a benign mass, such as fibroadenoma, because of the patient s age (44 years) and family history (her sister died of breast cancer at 46 years), histopathologic examination, which disclosed carcinosarcoma, was strongly recommended. reast-conserving surgery (lumpectomy with axillary node dissection) was performed in one patient who showed axillary lymph node involvement. Two years after surgery, she developed local recurrence, contralateral breast masses, supraclavicular lymphadenopathy, and pulmonary nodules consistent with metastasis, although metastatic disease was not proven histopathologically. The other seven patients were treated with modified radical mastectomy, with the axilla showing no metastatic involvement. Fine-needle aspiration cytology of the lesion that was available in one patient was diagnosed as malignant epithelial tumor. t histopathologic examination, the metaplastic components of the lesions were squamous cell type in three patients (Figs. 2C and 2D), matrix-producing type in two, carcinosarcomatoid in two (Figs. 3D and 3E), and a mixture of spindle cell and matrix-producing type in one. In the complex mass, which showed heterogenous echogenicity with solid and cystic components on sonography, necrosis and cystic degeneration were found at histopathology. ll eight patients underwent axillary lymph node dissection, and involvement was positive in only one JR:178, June 2002

3 Mammography and Sonography of Metaplastic Carcinoma C D Fig year-old woman with 2-cm, firm, mobile, and palpable left breast mass., Mediolateral oblique mammogram shows microlobulated, 2-cm round mass (arrows)., Transverse sonogram shows round, solid mass with homogeneous echogenicity and microlobulated margins (arrow). C, Photomicrograph shows mammarian ductulus on left side. On right side, metaplastic breast carcinoma and squamous cell groups can be seen. (H and E, 200) D, Photomicrograph shows squamous differentiation areas in metaplastic breast carcinoma. (H and E, 400) Discussion Metaplastic breast carcinomas are regarded as ductal carcinomas that undergo metaplasia into a nonglandular growth pattern [1, 6, 8]. The mixed cell origin is corroborated by histopathologic staining for mesenchymal cells (vimentin), epithelial cells (cytokeratin), and myoepithelial cells (S-100 protein, actin, and high-molecular-weight cytokeratin) [1]. Wargotz and Norris [3, 5, 15] and Wargotz et al. [4] suggested four variants of metaplastic carcinoma, including matrix-producing carcinoma, spindle cell carcinoma, squamous cell carcinoma, and carcinosarcoma. Oberman [6] suggested that all such tumors be categorized JR:178, June 2002 as metaplastic carcinoma of the breast, deemphasizing whether the metaplastic component is of mesenchymal or epithelial origin. lthough these rare tumors show pathologic features of both carcinoma and sarcoma, because metaplastic carcinoma with a sarcomatous component is a different entity from primary breast sarcoma, we believe differentiation is significant to characterize them as distinct entities for purposes of diagnosis, treatment, and prognosis. Metaplastic carcinomas are usually seen in women who are more than 50 years old [2, 3, 5, 6, 9]. The ages of our patients were between 44 and 63 years old; only two patients were less than 50 years old. The presenting symptom is usually a palpable mass, and axillary lymph node metastasis is infrequent [2 5]. ll our patients had palpable masses, and only one (12.5%) had axillary lymph node involvement. The number of our patients is too few to accurately determine the frequency of lymph node involvement in a larger patient population. The mammographic appearance of metaplastic breast carcinoma has been described in case reports or in small series [1, 8 13]. To our knowledge, only four reports have been published that correlate mammographic and pathologic features of this rare tumor [1, 8, 10, 12]. renner et al. [1], in their study of three 1423

4 Günhan-ilgen et al. C Fig year-old woman with 2-cm palpable left breast mass., Craniocaudal mammogram shows microlobulated, round mass (arrows)., Microlobulation of margins is better shown on spot mammogram. C, Transverse sonogram shows microlobulated hypoechoic solid mass. D, Photomicrograph shows admixture of cohesive carcinoma cells and malignant stromal spindle cells. (H and E, 200) E, Photomicrograph shows spindle cells in metaplastic carcinoma. (H and E, 400) D patients, described the mass as well circumscribed, irregular, or spiculated, whereas Patterson et al. [8], in their series on nine patients, reported a predominantly circumscribed, noncalcified mass with a spiculated portion. Samuels et al. [13] described the margins of five masses, which were oval, as indistinct and partially well circumscribed; in three of them, the tumor margin was also partly spiculated. Park et al. [10], in their study of 16 patients, described the characteristic appearance as an ill-defined or obscured round mass with associated architectural distortion. s for the presence of microcalcifications, Evans et al. [12], in their case report of osseous metaplasia, described a predominantly circumscribed mass with a densely calcified center and an osteoid matrix. renner et al. reported a 2-cm smooth mass with macrocalcifications, and Park et al. reported one patient with clustered microcalcifications without an associated mass. In our series, the margins of the tumors were either obscured (37.5%), microlobulated (37.5%), or well circumscribed (25%). ll the masses had high density without spiculations 1424 or associated microcalcifications on mammography. In contrast to the study of Park et al. [10], associated architectural distortion was not noted in our patients. When we compare and combine the mammographic findings of the masses in all the previously reported series and in this study, we could probably conclude that no specific or distinctive descriptor for mass margin is characteristic of metaplastic carcinoma. However, a high-density mass without associated microcalcifications might be useful in suggesting the diagnosis. lthough seen rarely and possibly not a characteristic finding, metaplastic carcinoma could be included in the differential diagnosis of predominantly circumscribed, noncalcified masses seen on mammography. Metaplastic carcinomas are likely to have circumscribed margins, especially when the tumor is composed solely of spindle cells [8]. In one of our patients, the mass was so well circumscribed that it mimicked a fibroadenoma. However, histopathologic examination disclosed carcinosarcoma. One important feature that may be helpful in distinguishing metaplastic carcino- E mas from predominantly circumscribed noncalcified masses is the concurrence of a circumscribed portion with a spiculated portion, which is seen in carcinomas with a mixture of growth patterns of metaplastic and invasive carcinoma not otherwise specified [8]. On sonographic examination, one of the masses showed complex internal echogenicity with solid and cystic components, which was consistent with necrosis and cystic degeneration at pathologic examination. The sonographic features of metaplastic carcinoma have been previously reported [10, 13]. Samuels et al. [13], in their study of five patients, of whom four had sonographic examinations, showed both cystic and solid components in two of the masses. The histopathologic diagnosis of these tumors was predominantly squamous cell carcinoma. Park et al. [10], in their study of 16 patients, of whom 11 had sonograms, observed complex internal echogenicity with solid and cystic components in six lesions. Four of these six lesions also had hemorrhagic or cystic necrosis at pathologic examination. We believe that metaplastic carcinoma, although a rare tu- JR:178, June 2002

5 Mammography and Sonography of Metaplastic Carcinoma mor, should be considered in the differential diagnosis of breast masses with solid and cystic components. In most metaplastic carcinomas, foci of transition between invasive ductal carcinoma and the metaplastic element are detected, sometimes only after extensive sampling. In tumors in which the metaplastic spindle component constitutes almost the entire tumor, the distinction from a sarcoma may be difficult. In some of these cases, ductal carcinoma in situ adjacent to the tumor often suggests that the spindle cells were of epithelial origin [8]. The diagnosis of metaplastic breast carcinoma may be made with aspiration cytology or core biopsy, but excisional biopsy is preferred because diagnostic errors resulting from inadequate samples are avoided, especially in cases of associated necrosis or hemorrhage [8, 12, 16]. Patterson et al. [8] have stated that the distinction between metaplastic breast cancer and sarcoma is clinically important because the surgical treatment, chemotherapy regimens, and metastatic pathways are different. Typically, axillary lymph node involvement is rare in breast sarcoma even when the disease is diffusely disseminated, whereas lymph node metastases are reported in 25 30% of cases with metaplastic carcinomas [1, 8]. ll eight patients in our series underwent axillary lymph node dissection, and metastasis was detected in only one patient (12.5%); at histopathologic examination, the metaplastic component of the tumor was carcinosarcomatoid type. However, the number of our cases is too few to accurately determine the frequency of lymph node involvement in a larger patient population. lthough no series has been sufficiently large to determine overall prognosis, survival most likely depends on tumor size, histologic type, grade, lymph node status, and perhaps most directly on the type and grade of the mesenchymal component. The overall 5- year survival rate is approximately 40% [1]. Chemotherapy is usually directed toward the sarcomatous component of the disease on the basis of the patterns of metastases [1]. In conclusion, metaplastic carcinoma of the breast manifests as a rapidly growing, palpable mass that has high density on mammography and may be microlobulated on sonography. Complex echogenicity with solid and cystic components may be seen sonographically and is related to necrosis and cystic degeneration found histopathologically. lthough metaplastic carcinoma is a rare breast malignancy, and these features are not unique, metaplastic carcinoma should be included in the differential diagnosis. References 1. renner RJ, Turner RR, Schiller V, rndt RD, Giuliano. Metaplastic carcinoma of the breast: report of three cases. Cancer 1998;82: Pitts WC, Rojas V, Gaffey MJ, et al. Carcinomas with metaplasia and sarcomas of the breast. m J Clin Pathol 1991;95: Wargotz ES, Norris HJ. Metaplastic carcinoma of the breast. I. Matrix-producing carcinoma. Human Pathol 1989;20: Wargotz ES, Deos PH, Norris HJ. Metaplastic carcinoma of the breast. II. Spindle cell carcinoma. Human Pathol 1989;20: Wargotz ES, Norris HJ. Metaplastic carcinoma of the breast. IV. Squamous cell carcinoma of ductal origin. Cancer 1990;65: Oberman H. Metaplastic carcinoma of the breast. m J Surg Pathol 1987;11: Feder JM, de Paredes ES, Hogge JP, Wilken JJ. Unusual breast lesions: radiologic pathologic correlation. RadioGraphics 1999;19[suppl]:S11 S26 8. Patterson SK, Tworek J, Roubidoux M, Helvie M, Oberman H. Metaplastic carcinoma of the breast: mammographic appearance with pathologic correlation. JR 1997;169: Taylor D, damson R, Minchin DE, Reading L. Carcinoma of the breast with sarcomatous metaplasia. ustralas Radiol 1994;38: Park JM, Han K, Moon WK, Choe YH, hn SH, Gong G. Metaplastic carcinoma of the breast: mammographic and sonographic findings. J Clin Ultrasound 2000;28: Tashjian J, Kuni CC, ohn LE. Primary squamous cell carcinoma of the breast: mammographic findings. Can ssoc Radiol J 1989;40: Evans H, Shaughnessy E, Nikiforov YE. Infiltrating ductal carcinoma of the breast with osseous metaplasia: imaging findings with pathologic correlation. JR 1999;172: Samuels TH, Miller N, Manchul L, DeFreitas G, Panzarella T. Squamous cell carcinoma of the breast. Can ssoc Radiol J 1996;47: merican College of Radiology. reast imaging reporting and data system (I-RDS), 3rd ed. Reston, V: merican College of Radiology, Wargotz ES, Norris HJ. Metaplastic carcinoma of the breast. III. Carcinosarcoma. Cancer 1989;64: Kline TS, Kline IK. Metaplastic carcinoma of the breast: diagnosis by aspiration biopsy cytology report of two cases and literature review. Diagn Cytopathol 1990;6:63 67 JR:178, June