A 55-year-old woman presented with a large palpable mass in her left breast, which she had discovered 1 year earlier and increased in size. The large heterogeneous hypoechoic mass in the left breast found on ultrasonography (Fig. 2A) showed remarkable FDG uptake on PET-CT (maxSUV, 12.39; Fig. 2D). Breast MRI showed a T1 iso-SI mass with early heterogeneous enhancement and early washout (Fig. 2B). Results of a subsequent diagnostic core biopsy revealed an adenosquamous carcinoma. Modified radical mastectomy was performed. Histopathologic examination of the resected specimen showed low-grade adenosquamous carcinoma. Skin invasion were observed. Both ER and PR were negative, and HER2 was positive (Table 1). The patient underwent preoperative adjuvant chemotherapy, followed by postoperative radiotherapy. Seven months later, the patient developed a right axilla recurrence and transferred to an outside hospital.
A 53-year-old woman presented with a palpable lump in the right breast, subareolar area. Mammography showed an indistinct oval hyperdense mass in the right breast, subareolar area (Fig. 3A). Ultrasonography revealed an indistinct angular hypoechoic mass and suspicious axillary lymph node (Figs. 3B, C). Subsequent diagnostic core biopsy of the tumor indicated squamous cell carcinoma. Immunohistochemistry of the tumor was negative for ER and PR and positive for HER2 (Table 1). She was transferred to an outside hospital.
A 46-year-old woman presented with a mass in the right breast, which was discovered during self-examination and stable for several months. She had an operation history of bilateral mammoplasty. Mammography showed an indistinct round hyperdense mass in the right breast, upper outer quadrant. Metastatic lymph node was also noted in right axilla (Fig. 4A). Ultrasonography showed a microlobulated, round, complex cystic and solid mass with metastatic lymph node (Figs. 4B, C), which showed remarkable FDG uptake on PET-CT (maxSUV, 11.4 and 10.5, respectively; Fig. 4E). Magnetic resonance imaging revealed a heterogeneous T2 high-SI mass with peripheral enhancement in the right breast, upper outer quadrant, which showed early enhancement in subtraction image and washout in reverse subtraction image, with metastatic lymph node of similar appearance (Figs. 4D). Subsequent diagnostic core biopsy revealed low-grade adenosquamous carcinoma and mixed metaplastic carcinoma. The tumor was negative for ER, PR, and HER2 (Table 1). The patient underwent adjuvant chemotherapy followed by lumpectomy and postoperative radiotherapy. Histopathologic examination of the resected specimen revealed no residual tumor and no metastatic axillary lymph nodes. Four months after operation, brain angio-CT showed 2 enhancing nodules that were suspicious for metastatic disease. The patient underwent palliative radiotherapy and has had stable disease for the past 8 months.
A 55-year-old woman presented with a palpable mass in the right breast. Mammography showed a microlobulated oval isodense mass in the right breast upper, outer quadrant (Fig. 5A). Ultrasonography show a partly angular oval hypoechoic mass with several satellite nodules in the right breast, upper outer quadrant, with suspicious lymph node in right axilla (Figs. 5B, C). Magnetic resonance imaging showed an irregular spiculated heterogeneous T2 high-, T1 low-SI mass with early enhancement and delayed washout (Fig. 5D). Positron emission tomography–CT showed remarkable FDG uptake in the main mass and satellite nodules in the right breast, upper outer quadrant (maxSUV, 12.16 and 5.25, respectively; Fig. 5E).
Subsequent diagnostic core biopsy revealed an invasive ductal carcinoma.
Modified radical mastectomy was performed. Histopathologic examination of the resected specimen showed low-grade adenosquamous carcinoma and mixed metaplastic carcinoma and invasive ductal carcinoma measuring 2.5 × 2.5 × 2.4 cm. Metastatic lymph nodes were absent, and the tumor was negative for ER and PR and positive for HER2 expression (Table 1). The patient subsequently received adjuvant chemotherapy. She has been free of recurrence during 7 months of follow-up.
Most benign and malignant tumors originate from glandular epithelium. In a small percentage of malignancies, glandular epithelium undergoes a process called metaplasia, presenting differentiation to nonglandular mesenchymal tissue.4 Metaplastic breast carcinoma is a rare subtype of ductal carcinoma undergoing metaplasia including squamous differentiation, a spindle-cell pattern of growth, and/or heterogeneous mesenchymal morphological elements.2,4,6 The most common metaplastic components include squamous metaplasia.4 Metaplastic breast carcinoma accounts for less than 5% of all breast cancers.1–6 It occurs more commonly in black and Hispanic women.11 Metaplastic breast carcinomas usually present in approximately 50-year-old women as a fast-growing palpable large mass, with lower rates of axillary nodal involvement, higher rates of both local recurrence and metastasis, and higher rates of ER, PR, and Her2 negativity, as well as a suboptimal response to systemic therapies when compared with other invasive breast cancers.4,6,9,10 It is often associated with poorer survival, despite the survival advantage of histologic-specific novel chemotherapeutic strategies and thus a potential area for further research.1 In the current study, we described 5 metaplastic breast carcinoma patients. The most common type of metaplastic carcinoma is known as squamous, followed by spindle cell and matrix producing. Osseous or sarcomatoid metaplasia is a rare type.4 In our study, low-grade adenosquamous carcinoma was noted in 2 cases, and low-grade adenosquamous carcinoma with mixed metaplastic carcinoma in 2 cases squamous cell carcinoma in 1 case. Moreover, most cases are not associated with hormone receptors. ER and PR were negative in 5 of our patients, whereas 3 of the tumors were positive for Her2. In addition, surgical specimen axillary lymph node metastases were noted in 1 case. Despite the poor prognosis of metaplastic breast carcinoma, reduced axillary node metastasis is observed due to its hematogenous over lymphatic spread. This may also result in higher rates of local or distant metastases during the follow-up.4 The results of our study are similar to those of previous reports.
On mammography, metaplastic breast carcinomas show a predominantly circumscribed, dense, noncalcified mass.2,4,6,11,12
On sonography, metaplastic breast carcinoma appears as gently lobulated complex echogenicity with solid components as well as cystic components that are related to necrosis and cystic degeneration in the histologic analysis.2,4,6,11 Posterior acoustic enhancement is common.4,10
Breast MRI could be used as a problem-solving tool with higher sensitivity and specificity in cases of equivocal findings with conventional breast imaging modalities.2 On magnetic resonance images, metaplastic breast carcinomas present as a round to lobular mass, frequently smooth margins, and generally isointense or hypointense, similar to other histologic types of invasive breast carcinoma. Nevertheless, high signal intensity on T2-weighted images due to necrotic component and cystic degeneration is a frequent finding.2,4,6,11 The T2 high signal is also observed in mucinous carcinoma, invasive ductal carcinoma with infarction or necrosis, intracystic papillary carcinoma, and invasive papillary carcinoma, in addition to metaplastic breast carcinoma.4,6 The reported enhancement characteristics of these lesions include heterogeneous, rim-like, or containing nonenhancing internal components. The frequently reported kinetic pattern is early enhancement and a delayed washout corresponding to the enhancing peripheral portion and nonenhancing internal components.2,4,12
The mammographic, sonographic, and MRI imaging characteristics of metaplastic breast carcinomas can be similar to invasive ductal carcinoma as well as benign lesion, and so subject to misinterpretation.4,12 Overlapping findings prevent complete differentiation of such tumors on imaging.2,4 Awareness of the overlapping imaging findings and clinical features can assist in diagnosing these malignancies.12
Metaplastic breast carcinomas should be differentiated from invasive ductal carcinoma and primary breast sarcoma, to determine appropriate treatment options and management.2,12,13 Preoperative diagnosis of metaplastic breast carcinoma by core needle biopsy might be possible, but in most cases, transition foci of metaplastic element were noted after excision biopsy. Therefore, extensive sampling such as excision biopsy should be performed to avoid misleading from small sample.4
In conclusion, metaplastic breast carcinoma is a rare subtype of breast cancer accounting for less than 5% of all breast cancers. It is characterized by a larger size at presentation, lower rates of axillary nodal involvement, higher rates of both local and distant recurrence, and higher rates of ER, PR, and Her2 negativity. Most metaplastic breast carcinomas have a poor prognosis due to a suboptimal response to systemic therapy. On mammography and sonography, metaplastic breast carcinoma shows benign features including circumscribed margin, round shape, and posterior acoustic enhancement. T2 high signal intensity, early enhancement, and a delayed washout in a peripheral rim and nonenhancing internal components on magnetic resonance image would be helpful in differentiating from other breast malignancies. Therefore, multimodality imaging studies with immunohistochemical and pathologic studies are necessary in the diagnosis of metaplastic breast carcinoma. Further research studies may be required to develop a targeted therapeutic regimen for improving clinical outcomes.
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8. Frank GA, Danilova NV, Andreeva IuIu, et al. WHO classification of tumors of the breast, 2012. Arkh Patol
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11. Ryckman EM, Murphy TJ, Meschter SC, et al. AIRP best cases in radiologic-pathologic correlation: metaplastic squamous cell carcinoma of the breast. Radiographics
12. Leddy R, Irshad A, Rumboldt T, et al. Review of metaplastic carcinoma of the breast: imaging findings and pathologic features. J Clin Imaging Sci
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Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved
metaplastic breast carcinoma; MRI; CT; sonography; mammography; PET-CT