ORIGINAL ARTICLE
Imaging Manifestation of Adenoid Cystic Carcinoma of the Breast Wei Tang, MD,*† Wei Jun Peng, MD,*† Ya Jia Gu, MD,*† Hui Zhu, MD,*† Ting Ting Jiang, MM,*† and Can Li, MM†‡ Objective: This study aimed to describe the imaging features of adenoid cystic carcinoma (ACC) of the breast using multimode imaging. Materials and Methods: The findings from mammography, sonography, magnetic resonance imaging, or digital breast tomosynthesis in 11 patients with histopathologically confirmed ACC of the breast were reviewed. The imaging criteria included location, shape, size, number, margin, calcification, attenuation, echo and/or signal intensity, internal mass enhancement pattern, and dynamic-enhancement characteristics. Results: On mammography (n = 9), ACC demonstrated as an irregular or lobulated mass with indistinct or spiculated margins. Sonographically (n = 11), ACCs appeared as a hypoechoic solid or heterogeneous mass with minimum vascularity on color Doppler examination. With regard to magnetic resonance imaging (n = 9), 2 of the largest masses had an extensive high T2-weighted imaging (T2WI) signal and hypointense internal septations, which demonstrated delayed enhancement. Dynamic enhancement illustrated washout kinetics. The 7 smaller masses appeared isointense on T2WI, and their internal septations were unenhanced. Among them, 5 demonstrated plateau kinetics and 2 demonstrated persistent kinetics. Conclusions: Although ACC is a rare event in the breast, we believe that the following signs may suggest the diagnosis of this entity: a well-defined border, extensive high T2WI signals, and internal septations that demonstrate delayed enhancement in larger lesions. Key Words: adenoid cystic carcinoma, breast, mammography, sonography, magnetic resonance imaging, digital breast tomosynthesis (J Comput Assist Tomogr 2015;39: 523–530)
A
denoid cystic carcinoma (ACC) is most commonly observed as a tumor of the salivary glands, but it also arises in breast tissue.1 Adenoid cystic carcinoma of the breast is a particularly uncommon subtype of breast cancer and constitutes roughly 0.1% of all breast malignancies.2 Although it parallels ACC of the salivary glands with respect to microscopic characteristics, immunologic phenotypes and even the molecular genetic defect, the biological behavior of these 2 entities is different.3,4 Adenoid cystic carcinoma of the breast carries a more favorable prognosis than that of the salivary glands.5 Adenoid cystic carcinoma of the breast is frequently negative for estrogen receptor (ER) and progesterone receptor (PR) proteins, and Her-2 gene amplification (triple-negative).6 Interestingly, unlike the poor prognosis that is associated with other triple-negative breast cancers, ACC has been
reported to have excellent outcomes. The incidence of axillary lymph node involvement and distant metastases is low.7 The imaging characteristics of ACC of the breast have not been well described in the writing due to its uncommonness. However, some nonspecific imaging features of this disease have been described. It can appear as a lobulated or irregular mass with circumscribed, microlobulated, obscured, or spiculated margins on mammography.8,9 It often presents as a hypoechoic solid or heterogeneous mass with sharp or obscured margins on sonography.10,11 As far as we know, the magnetic resonance imaging (MRI) characteristics of ACC of the breast were only published in a few case reports and one article with a small sample size. In this study, we collected 11 cases with pathologically confirmed ACC of the breast to describe the imaging findings of multiple imaging techniques.
MATERIALS AND METHODS Patient Data This study was approved by our institutional review board, and written informed consent was obtained from all patients. The data from 11 patients with histopathologically proven ACC of the breast for 6 years (September 2008 through September 2014) were retrospectively reviewed. The population of our study was composed of 11 patients, including 10 female patients and 1 male patient. The average age of female patients was 54 years (range, 34–64 years); the male patient was 78 years old. Four patients were premenopausal at the time of diagnosis. Mammographic and sonographic images were available in all patients. Moreover, MRI images of 9 patients were accessible. One patient also underwent digital breast tomosynthesis (DBT) examination. The tumors were removed in all cases using the following approaches: modified radical mastectomy (n = 5), simple mastectomy (n = 4), and lumpectomy (n = 2). Six patients underwent an axillary sentinel node biopsy, and 5 patients underwent an axillary lymph node dissection. A subset of cases received adjuvant radiotherapy (n = 2) and chemotherapy (n = 5) after surgery. Endocrine therapy was not given to any of the patients. The details of the surgical approaches and the various therapies are shown in Table 1.
Imaging Techniques From the *Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China; †Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; and ‡Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. Received for publication December 14, 2014; accepted January 29, 2015. Reprints: Wei Jun Peng, MD, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Rd, Xuhui District, Shanghai 200032, China (e‐mail: [email protected]). Contract grant sponsor: This work was supported by the National Natural Science Foundation of China (Grant Nos. 81172073, 30470543, 30670597). The authors declare no conflict of interest. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Mammography and DBT Modalities Eleven patients underwent mammography on 2 units (MAMMOMAT Inspiration; Siemens, Erlangen, Germany [n = 5]; Selenia, Hologic, Boston, MA [n = 6]) where images of mediolateral oblique (MLO) and craniocaudal views were obtained. In addition, 1 patient also underwent DBT (MAMMOMAT Inspiration; Siemens) after mammography. During tomosynthesis imaging, 50 projections were acquired over a 50° angular range (−25° to +25°). These projections were then used to reconstruct tomographic images of the breast with a slice thickness of 1 mm.
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TABLE 1. Data of Clinical Findings
Sex/Age, y
Menopausal Status
1
F/59
Postmenopausal
2 3 4 5
F/59 F/56 F/46 M/78
Postmenopausal Postmenopausal Premenopausal None
6 7 8 9 10
F/50 F/62 F/34 F/50 F/60
Premenopausal Postmenopausal Premenopausal Premenopausal Postmenopausal
11
F/64
Postmenopausal
Patient
Symptoms Palpable mass with pain Palpable mass Palpable mass Palpable mass Palpable mass with pain Palpable mass Palpable mass Palpable mass Without symptoms Palpable mass with pain Palpable mass
Size (cm)
Axillary Management
MRM
1.7
SLNB
No
72
SM Lumpectomy MRM SM
1.2 1.6 5.5 2.0
ALND SLNB ALND SLNB
No No RT and CT CT
45 41 34 32
MRM SM MRM SM Lumpectomy
2.8 2.2 1.0 1.5 1.6
ALND SLNB SLNB ALND SLNB
RT and CT CT No No No
28 24 19 18 15
MRM
2.0
ALND
CT
Surgery
Adjuvant Treatment
Follow-up Time, mo
2
ALND indicates axillary lymph node dissection; CT, chemotherapy; F, female; M, male; MRM, modified radical mastectomy; RT, radiotherapy; SLNB, sentinel lymph node biopsy; SM, simple mastectomy.
Sonography
Image Analysis
All patients were examined via grayscale and color Doppler interrogation to characterize the lesions. The ultrasound machine used was the IU 22 (Philips, Bothell, WA), which is equipped with a 5- to 12-MHz linear array probe. The focus depth was located near the area of interest. The subsequent settings were used: mechanical index, 0.4–0.8; dynamic range, 50–80; and frame rate, 10–20.
The images acquired during mammography, DBT, sonography, and MRI were reviewed until an agreement was reached by 2 experienced mammoradiologists who did not know the pathological diagnosis. All images that were obtained via mammography, DBT, sonography, and MRI were analyzed according to the Breast Imaging Reporting And Data System (BI-RADS 2013, American College of Radiology), which included the following imaging criteria of the lesions: (1) location; (2) shape (eg, round, oval, lobulated, or irregular); (3) size; (4) number; (5) margin (eg, smooth, obscure, irregular, or spiculated); (6) calcification (ie, distribution and appearance); (7) attenuation, echo, and signal intensity; (8) internal enhancement pattern of the mass (eg, homogenous, heterogeneous, rim enhancement, dark internal septations, enhancing internal septations, and central enhancement); and (9) dynamic-enhancement characteristics (eg, persistent curve, plateau curve, and washout curve).
Magnetic Resonance Imaging Nine patients underwent a contrast-enhanced bilateral breast MRI examination in a prone position on different units before surgery. Five examinations were performed with a 3.0-T unit (Signa HDxt; GE Healthcare, Milwaukee, WI), and 4 examinations were performed with a 1.5-T unit (Signa Excite; GE Healthcare), which used a dedicated breast coil (LIBERTY 9000 8-Channel Breast Coil for 1.5-T unit, HD 8-Channel Volume Imaging For Breast Assessment [Vibrant] Breast Array for 3.0-T unit). The unenhanced MRI scan consisted of a localizer sequence, an axial STIR sequence and a T1 fast spin echo (FSE) sequence. The following scan parameters were used: repetition time (TR)/echo time (TE) of 800–900 milliseconds/8.7–10.2 milliseconds for T1weighted imaging (T1WI), TR/TE of 3500–4000 milliseconds/ 80–100 milliseconds for STIR, 2 to 4 excitations, a matrix of 256 256, field of view of 26 26 cm, section thickness of 3 mm, and an intersection gap of 0.6 mm. Gadopentetate dimeglumine (Magnevist; Bayer Schering Pharma, Berlin, Germany) was administered intravenously at a flow rate of 2 mL/s (total dose, 0.2 mmol/kg of body weight) with a highpressure syringe (Dptistar Elite; Liebel-Flarsheim, Cincinnati, OH) and was followed by a 20-mL saline flush. A series of six 1-minute postaxial T1 fat-suppressed enhanced images were acquired with a Vibrant sequence. In addition, delayed highresolution sagittal T1 fat-suppressed enhanced images were also obtained using a sagittal Vibrant sequence. The scan parameters were as follows: TR/TE of 6.2–8.6 milliseconds/3.1–4.0 milliseconds, 1 excitation, matrix of 256 256, field of view of 32 32 cm, section thickness of 2 mm, and intersection gap of 0 mm. Threedimensional Maximum Intensity Projection reconstructions were performed when necessary.
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Pathological Technology All of the pathological specimens were reviewed retrospectively by a pathologist with expertise in breast tumors. All specimens were fixed in 15% buffered formalin and embedded in paraffin. Five-micrometer-thick sections were stained with hematoxylin and eosin after cutting from all tissue samples. Immunohistochemical stains for ACC of the breast were performed in all cases, including stains for ER, PR, Her-2 protein, Ki67, C-kit protein (CD117), cytokeratin (CK) 5/6, CK14, calponin, epithelial membrane antigen, and P63. The pathologist and the 2 radiologists found a correlation between the imaging findings and the pathological findings.
RESULTS Clinical Information Ten patients firstly sought medical help for a palpable mass, and 3 of them presented with accompanying focal pain. One patient was asymptomatic, and the diagnosis of ACC was an incidental finding during a routine health examination. All lesions were solitary and their locations varied: in 5 cases, 3 cases, 2 cases, © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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and 1 case, the lesion was located in the subareolar area, the lower outer quadrant, the upper inner quadrant, and the upper outer quadrant, respectively (Table 2). The median tumor size was 2.1 cm (range, 1.0–5.5 cm) in our series. All patients in our study firstly demonstrated as localized disease and without axillary lymph node metastases. All patients of our study are on follow-up, the time ranged from two months to six years (mean, 30 months). They all underwent diagnostic mammography and sonography every six months, one patient also underwent MRI. All patients had an excellent outcomes, and so far, none of the patients has appeared as a local recurrence or died from complications of her/his disease.
Imaging Characteristics In our study, the sonographic characteristics of ACC of the breast were a hypoechoic solid or heterogeneous mass with a poorly defined border. Echogenic halo and posterior acoustic shadowing were not seen in any of the cases (Figs. 1B, 2B, 3D, and 4B). The margins of masses were not well circumscribed but, rather, were angular (n = 2), indistinct (n = 3), or microlobulated (n = 6). All patients underwent the color Doppler interrogation, and all masses demonstrated minimal vascularity (Figs. 1B, 2B, and 4B). Mammograms were available for all patients, and masses were identified in 9 cases (Figs. 1A, 2A, and 3A). The mass appeared as a lobular or irregular shape with microlobulated, indistinct, or spiculated margins. The male patient presented with an asymmetric dense lesion in the subareolar area (Fig. 4A). One patient with dense breast tissue presented with a palpable mass, but no lesion was identified on mammography. No calcification was found in any case. On the basis of the mammographic
Adenoid Cystic Carcinoma of the Breast
findings, these 10 abnormal cases were considered as BI-RADS category 4 or 5. In addition to conventional mammography, 1 of 11 patients underwent DBT (Fig. 3B). On MRI, 9 masses appeared with a lobulated (n = 3), oval (n = 4), or irregular (n = 2) shape with smooth margins (n = 7) or spiculated (n = 2) margins. Compared with normal glandular tissue, all lesions appeared homogeneously isointense on T1WI (Figs. 1C and 2D). After the injections of contrast agent, the enhancement of all masses was rapid and heterogeneous (n = 4; Fig. 1E) or rapid and homogenous (n = 5; Figs. 2E and 3C). On T2-weighted imaging (T2WI), the larger masses had relatively characteristic findings: 2 of the largest masses (diameter, 5.5 and 2.3 cm) in our series had extensive high T2WI signals and hypointense internal septations (Fig. 1D). These 2 masses demonstrated washout kinetics (Fig. 1G). Significantly, the aforementioned internal septations that were present in the larger masses were enhanced during the delayed phase (Fig. 1F). With regard to the 7 smaller masses, they appeared isointense on T2WI and their internal septations were not enhanced (Figs. 2C, E, and F and 3C). Five cases demonstrated plateau enhancement kinetics (Fig. 2G), and 2 cases demonstrated persistent kinetics. Axillary lymphadenopathy was not observed in any patient who underwent MRI.
Pathological Findings In this study, 11 cases of ACC of the breast were diagnosed. The microscopic manifestation of all specimens revealed the characteristic appearances of ACC in the breast: the epithelial (luminal) and myoepithelial (basaloid) proliferating cells surrounded by pseudocystic spaces were observed in a tumor. Meanwhile, 3 cytoarchitectural patterns were observed such as cribriform,
TABLE 2. Data of Imaging Findings Mammography
Sonography
Patient Location Attenuation Calcification
MRI
Echo
Shape
Margin
Lobulated
Smooth
1
SA
HI
None
Hypoecho
2
UOQ
HI
None
Hypoecho
3
LOQ
Negative
None
Hypoecho
4
LOQ
HI
None
Hypoecho
5 6
SA UIQ
AD HI
None None
Hypoecho Hypoecho
7 8
SA SA
HI HI
None None
Hypoecho Hypoecho
9
UIQ
HI
None
Hypoecho
10
LOQ
HI
None
Hypoecho
11
SA
HI
None
Hypoecho
Signal Intensity
Isointensity on T1WI and T2WI Irregular Smooth Isointensity on T1WI and T2WI Lobulated Smooth Isointensity on T1WI and T2WI Oval Smooth Isointensity on T1WI Hyperintensity on T2WI None None None Irregular Spiculated Isointensity on T1WI Hyperintensity on T2WI None None None Lobulated Smooth Isointensity on T1WI and T2WI Oval Smooth Isointensity on T1WI and T2WI Lobulated Spiculated Isointensity on T1WI and T2WI Oval Smooth Isointensity on T1WI and T2WI
Internal Enhancement
Curve
Rapid and heterogeneous Rapid and homogeneous Rapid and homogeneous Rapid and heterogeneous
Persistent
None Rapid and heterogeneous
None Persistent
None Rapid and homogeneous Rapid and homogeneous Rapid and homogeneous Rapid and heterogeneous
None Plateau
Plateau Plateau Washout
Plateau Plateau Washout
AD indicates asymmetric dense; HI, hyperintense; LOQ, lower outer quadrant; SA, subareolar area; UIQ, upper inner quadrant; UOQ, upper outer quadrant.
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FIGURE 1. A 46-year-old woman with ACC of the right breast. A, An MLO image from a diagnostic mammography shows an irregular mass with a circumscribed margin (arrows) in the subareolar area. B, A sonogram shows an irregular, ill-defined, hypoechoic mass with minimal vascularity on color Doppler interrogation. C, Axial, FSE, T1-weighted MR image of the right breast shows an irregular mass with homogeneous isointensity. D, Axial, STIR, T2-weighted MR image shows an irregular mass with extensive high signal intensity (short arrow) and hypointense internal septations (long arrow). E and F, Axial contrastenhanced MR image with fat saturation illustrates rapid heterogeneous tumor enhancement and enhancement of internal septations in the delayed phase (arrows). G, The mass demonstrated kinetics with a washout pattern. H, 100 magnification of the breast mass shows the cribriform growth pattern, neural invasion, and fibrous septum (arrow). H&E stain. I, 100 magnification of the positive immunohistochemical results for CK14. H&E, hematoxylin and eosin; MR, magnetic resonance. Figure 1 can be viewed online in color at www.jcat.org.
beam-tubular, and solid (Figs. 1H, 2H, 3E, and 4C). CD117 expression showed a significant diffuse membranous pattern in cases of ACC; all cases were positive for CD117 in our study (Figs. 2I and 3F). In addition, CK5/6, CK14 (Figs. 1I and 4D), epithelial membrane antigen, P63, and calponin were focally expressed in patients with ACC. Moreover, staining for ER, PR, and Her-2 protein was performed in all cases. Five cases were negative for the above, but in 2 cases, nuclear positivity for PR was
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observed in scattered neoplastic cells; weak positivity was noted in the cell membrane for Her-2 protein in 3 cases, and only 1 case showed weak staining for these 3.
DISCUSSION Adenoid cystic carcinoma most frequently occurs in the salivary glands, but it also occurs in the breast, lacrimal glands, © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Adenoid Cystic Carcinoma of the Breast
FIGURE 2. A 60-year-old woman with ACC of the right breast. A, An MLO image with an irregular mass and a circumscribed margin (arrows) in the lower outer quadrant. B, A sonogram demonstrates an irregular, well-defined, hypoechoic mass with minimal vascularity on color Doppler interrogation. C, Axial, STIR, T2-weighted MR image of the right breast shows an irregular mass with hypointense internal septations (arrow). D, Axial, FSE, T1-weighted MR image illustrates an irregular mass with homogeneous isointensity. E, Axial contrastenhanced MR image shows rapid homogeneous tumor enhancement and nonenhancement of internal septations in the delayed phase. F, Sagittal contrastenhanced MR image with fat saturation shows nonenhancement of internal septations in the delayed phase. G, This mass demonstrated plateau kinetics. H, 200 magnification of small tumor cells of ACC of the breast that form a solid or tubular growth pattern. H&E stain. I, 200 magnification of positive immunohistochemical results for CD117. H&E, hematoxylin and eosin; MR, magnetic resonance. Figure 2 can be viewed online in color at www.jcat.org.
auditory canal, digestive tract, skin, prostate, and Bartholin glands.12 Adenoid cystic carcinoma of the breast is a particularly rare subtype of malignant breast tumors and accounts for less than 0.1% of all breast carcinomas.2 Although it occurs mainly in women, male patients have been also reported.13,14 In our series, a 78-year-old male patient was diagnosed as having this disease. Although this disease can occur in any age, more cases are diagnosed in women who are 50 or 60 old.15 Consistent with the current
literature, the median age of the 10 female patients in this study was 54 years (range, 34–64 years). Clinically, the mainly symptom is a palpable mass in the breast. Breast pain and nipple retraction are also observed in some patients.16 In our series, 10 patients had a palpable mass, and 3 of them presented with focal pain. Nipple retraction was not observed in any patient. The tumor has been reported to occur mostly in the subareolar area,17 which was consistent with our
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FIGURE 3. A 34-year-old woman with ACC of the right breast. A, An MLO image shows a lobulated mass with spiculated margins (arrow) in the upper inner quadrant. B. An MLO DBT image demonstrates the clearer margin of the mass (arrow). C, Axial contrastenhanced MR image shows rapid homogeneous tumor enhancement and nonenhancement of internal septations in the delayed phase (arrow). D, A sonogram shows a lobulated, ill-defined, hypoechoic mass. E, 200 magnification of islands of cells with a characteristic cribriform pattern and a fibrous desmoplastic background. H&E stain. F, 200 magnification of positive immunohistochemical results for CD117. H&E, hematoxylin and eosin; MR, magnetic resonance. Figure 3 can be viewed online in color at www.jcat.org.
study (5 of 11 cases had tumors in this location). The biological behavior of ACC in the breast and salivary glands is quite different. Perineural invasion is not found in ACC of the breast, but most often observed in ACC of the salivary glands. The prognosis of patients with ACC in the breast and salivary glands is quite
different: the 5-year survival rates ranged from 90% to 100% and 45% to 64%, respectively.18 Histologically, ACC is a tumor composed of luminal and myoepithelial cellular proliferation which surrounded by pseudocystic spaces. Several cytoarchitectural forms have been observed (tubular, cribriform, and solid), and a
FIGURE 4. A 78-year-old man with ACC of left breast. A, An MLO image shows asymmetric density in subareolar area. B. A sonogram shows irregular, ill-defined, hypoechoic mass with minimal vascularity on color Doppler interrogation. C, 100 magnification of the classic cribriform growth pattern of ACC invading the breast parenchyma. H&E stain. D, 100 magnification of positive immunohistochemical results for CK14. H&E, hematoxylin and eosin. Figure 4 can be viewed online in color at www.jcat.org.
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mixture of them is commonly observed.19 Immunohistochemical studies have shown that ACC of the breast has a characteristic phenotype that is negative for ER, PR, and Her-2 proteins and positive for c-KIT protein.20In our series, 5 lesions were triple negative, 3 lesions were weakly positive for PR, 2 lesions were weakly positive for Her-2 protein, and 1 lesion was weakly positive for all of them. Unlike the poor prognosis that is associated with other triple-negative breast cancers, ACC has been reported to have an excellent survival rate despite its malignant nature.21 Distant metastases and involvement of the axillary nodes are very rare, which is in accordance with our study. Arpino et al22 found that a minority of patients had distant metastases and deaths (7.6% and 3.3%, respectively). In our study, all patients have favorable outcome, and so far, every patient is alive without any complication. The ACC of the breast has been described as a hypoechoic and heterogeneous mass with unsharp margins, which is consistent with our study.10,11,23 All of the tumors in our series demonstrated color Doppler interrogation with minimal peripheral color flow. It has been described as a benign-appearing smooth, lobulated, or an irregular mass on mammography,8–10,23 which is also consistent with what was observed in our study. One patient in our series had a tangible mass, but no lesion was observed on mammography; this might have been caused by the highly dense breast tissue that covered the mass. To our knowledge, the manifestation of ACC of the breast is controversial on MRI. Some scholars24,25 have described it as a round, oval, or irregular lesion with rapid enhancement (no washout) that extends from the margin to the center over time.8 Unlike the former, Glazebrook et al23found that on MRI, the masses appeared as irregular shapes with spiculated margins. Unenhanced scans showed that 2 of the largest masses demonstrated extensive hyperintensity on T2WI and that the 2 smaller masses demonstrated isointensity on T2WI. In addition, enhanced scans showed suspicious malignant enhancement. Compared with the findings of Glazebrook et al, only one sign was consistent with ours: the larger mass with extensive T2WI hyperintensity and the smaller mass with T2WI isointensity. In contrast to the findings of Glazebrook et al, most of our cases presented with benignappearing lesions (4 of 9 had oval shapes, and 7 of 9 had smooth margins). Moreover, we found that all masses had internal septations with low signal on T2WI and that the internal septations in the larger masses were enhanced in the delayed phase. We speculated that the internal septations observed on T2WI may correspond to the stroma embedded within the tumor islands (Fig 1I). Imaging findings may help to distinguish ACC of the breast from infiltrating ductal carcinoma (IDC) and fibroadenoma of the breast. Most cases of ACC of the breast have well-defined margins, whereas most cases of IDC have spiculated or irregular margins. On T2WI, the larger lesions of ACC of the breast demonstrated an extensive high signal, whereas IDC and fibroadenoma appeared as hypointense or isointense in most cases. Some fibroadenoma may overlap ACC, especially in small lesions, they both have benign imaging manifestations. However, the larger lesions of ACC usually have obvious heterogeneous high T2WI signals whereas the signals of fibroadenoma are homogeneous in most cases. Furthermore, some fibroadenomas have non-enhancing internal septations, while the internal septations of ACC have been described as delay-enhanced, especially in the larger lesions. Overall, ACC is a rare type of breast cancer, We described some relative useful imaging manifestations to help to make the diagnosis. However, in some really overlapped lesions, the core biopsy is needed.25 Our study had several limitations. A predominant limitation was the small sample size owing to the scarcity of the tumors that
Adenoid Cystic Carcinoma of the Breast
formed the basis of the imaging review. This resulted in a lack of statistical significance. Another limitation was a lack of consistent imaging parameters due to the length and the depth of time when the cases were collected. In addition, some of the imaging findings were nonspecific. Nevertheless, we consider that some valuable manifestations emerged on MRI: most lesions of ACC in the breast are well defined; on T2WI, the larger ACCs of the breast might show extensive high signal and hypointense internal septations, which could enhance in the delayed phase. REFERENCES 1. Sarnaik AA, Meade T, King J, et al. Adenoid cystic carcinoma of the breast: a review of a single institution's experience. Breast J. 2010;16:208–210. 2. Kulkarni N, Pezzi CM, Greif JM, et al. Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base. Ann Surg Oncol. 2013;20:2236–2241. 3. Vranic S, Bender R, Palazzo J, et al. A review of adenoid cystic carcinoma of the breast with emphasis on its molecular and genetic characteristics. Hum Pathol. 2013;44:301–309. 4. Persson M, Andren Y, Mark J, et al. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A. 2009;106:18740–18744. 5. Soon SR, Yong WS, Ho GH, et al. Adenoid cystic breast carcinoma: a salivary gland-type tumour with excellent prognosis and implications for management. Pathology. 2008;40:413–415. 6. Boujelbene N, Khabir A, Boujelbene N, et al. Clinical review—breast adenoid cystic carcinoma. Breast. 2012;21:124–127. 7. Kim M, Lee DW, Im J, et al. Adenoid cystic carcinoma of the breast: a case series of six patients and literature review. Cancer Res Treat. 2014; 46:93–97. 8. Okamoto Y, Sumiyama Y, Arima Y, et al. A case of adenoid cystic carcinoma (ACC) of the breast and review of the utility of preoperative imaging diagnose. Breast Cancer. 2001;8:84–89. 9. Santamaria G, Velasco M, Zanon G, et al. Adenoid cystic carcinoma of the breast: mammographic appearance and pathologic correlation. Am J Roentgenol. 1998;171:1679–1683. 10. Sperber F, Blank A, Metser U. Adenoid cystic carcinoma of the breast: mammographic, sonographic, and pathological correlation. Breast J. 2002;8:53–54. 11. Dinkel HP, Clees M, Gassel AM. Role of sonography in detecting recurrence in adenoid cystic carcinoma of the breast. Am J Roentgenol. 1999;173:497–498. 12. Xue Y, Liu X, Poplack S, Memoli VA. Adenoid cystic carcinoma of the breast in reduction mammoplasty. Breast J. 2012;18:611–613. 13. Kshirsagar AY, Wader JV, Langade YB, et al. Adenoid cystic carcinoma of the male breast. Int Surg. 2006;91:234–236. 14. Yoo SJ, Lee DS, Oh HS, et al. Male breast adenoid cystic carcinoma. Case Rep Oncol. 2013;6:514–519. 15. Bhosale SJ, Kshirsagar AY, Patil RK, et al. Adenoid cystic carcinoma of female breast: a case report. Int J Surg Case Rep. 2013;4:480–482. 16. Silva I, Tome V, Oliveira J. Adenoid cystic carcinoma of the breast with cerebral metastisation: a clinical novelty. BMJ Case Rep. 2011. doi: 10.1136/bcr.08.2011.4692. 17. Torrao MM, da Costa JM, Ferreira E, et al. Adenoid cystic carcinoma of the breast. Breast J. 2007;13:206. 18. Marchio C, Weigelt B, Reis-Filho JS. Adenoid cystic carcinomas of the breast and salivary glands (or ‘The strange case of Dr Jekyll and Mr Hyde’ of exocrine gland carcinomas). J Clin Pathol. 2010;63:220–228. 19. Defaud-Henon F, Tunon-de-Lara C, Fournier M, et al. Adenoid cystic carcinoma of the breast: clinical, histological and immunohistochemical characterization. Ann Pathol. 2010;30:7–16.
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20. Cadoo KA, McArdle O, O'Shea AM, et al. Management of unusual histological types of breast cancer. Oncologist. 2012;17:1135–1145.
23. Glazebrook KN, Reynolds C, Smith RL, et al. Adenoid cystic carcinoma of the breast. Am J Roentgenol. 2010;194:1391–1396.
21. Ghabach B, Anderson WF, Curtis RE, et al. Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study. Breast Cancer Res. 2010;12:R54.
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22. Arpino G, Clark GM, Mohsin S, et al. Adenoid cystic carcinoma of the breast: molecular markers, treatment, and clinical outcome. Cancer. 2002; 94:2119–2127.
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Imaging Manifestation of Adenoid Cystic Carcinoma of the Breast Wei Tang, MD,*† Wei Jun Peng, MD,*† Ya Jia Gu, MD,*† Hui Zhu, MD,*† Ting Ting Jiang, MM,*† and Can Li, MM†‡ Objective: This study aimed to describe the imaging features of adenoid cystic carcinoma (ACC) of the breast using multimode imaging. Materials and Methods: The findings from mammography, sonography, magnetic resonance imaging, or digital breast tomosynthesis in 11 patients with histopathologically confirmed ACC of the breast were reviewed. The imaging criteria included location, shape, size, number, margin, calcification, attenuation, echo and/or signal intensity, internal mass enhancement pattern, and dynamic-enhancement characteristics. Results: On mammography (n = 9), ACC demonstrated as an irregular or lobulated mass with indistinct or spiculated margins. Sonographically (n = 11), ACCs appeared as a hypoechoic solid or heterogeneous mass with minimum vascularity on color Doppler examination. With regard to magnetic resonance imaging (n = 9), 2 of the largest masses had an extensive high T2-weighted imaging (T2WI) signal and hypointense internal septations, which demonstrated delayed enhancement. Dynamic enhancement illustrated washout kinetics. The 7 smaller masses appeared isointense on T2WI, and their internal septations were unenhanced. Among them, 5 demonstrated plateau kinetics and 2 demonstrated persistent kinetics. Conclusions: Although ACC is a rare event in the breast, we believe that the following signs may suggest the diagnosis of this entity: a well-defined border, extensive high T2WI signals, and internal septations that demonstrate delayed enhancement in larger lesions. Key Words: adenoid cystic carcinoma, breast, mammography, sonography, magnetic resonance imaging, digital breast tomosynthesis (J Comput Assist Tomogr 2015;39: 523–530)
A
denoid cystic carcinoma (ACC) is most commonly observed as a tumor of the salivary glands, but it also arises in breast tissue.1 Adenoid cystic carcinoma of the breast is a particularly uncommon subtype of breast cancer and constitutes roughly 0.1% of all breast malignancies.2 Although it parallels ACC of the salivary glands with respect to microscopic characteristics, immunologic phenotypes and even the molecular genetic defect, the biological behavior of these 2 entities is different.3,4 Adenoid cystic carcinoma of the breast carries a more favorable prognosis than that of the salivary glands.5 Adenoid cystic carcinoma of the breast is frequently negative for estrogen receptor (ER) and progesterone receptor (PR) proteins, and Her-2 gene amplification (triple-negative).6 Interestingly, unlike the poor prognosis that is associated with other triple-negative breast cancers, ACC has been
reported to have excellent outcomes. The incidence of axillary lymph node involvement and distant metastases is low.7 The imaging characteristics of ACC of the breast have not been well described in the writing due to its uncommonness. However, some nonspecific imaging features of this disease have been described. It can appear as a lobulated or irregular mass with circumscribed, microlobulated, obscured, or spiculated margins on mammography.8,9 It often presents as a hypoechoic solid or heterogeneous mass with sharp or obscured margins on sonography.10,11 As far as we know, the magnetic resonance imaging (MRI) characteristics of ACC of the breast were only published in a few case reports and one article with a small sample size. In this study, we collected 11 cases with pathologically confirmed ACC of the breast to describe the imaging findings of multiple imaging techniques.
MATERIALS AND METHODS Patient Data This study was approved by our institutional review board, and written informed consent was obtained from all patients. The data from 11 patients with histopathologically proven ACC of the breast for 6 years (September 2008 through September 2014) were retrospectively reviewed. The population of our study was composed of 11 patients, including 10 female patients and 1 male patient. The average age of female patients was 54 years (range, 34–64 years); the male patient was 78 years old. Four patients were premenopausal at the time of diagnosis. Mammographic and sonographic images were available in all patients. Moreover, MRI images of 9 patients were accessible. One patient also underwent digital breast tomosynthesis (DBT) examination. The tumors were removed in all cases using the following approaches: modified radical mastectomy (n = 5), simple mastectomy (n = 4), and lumpectomy (n = 2). Six patients underwent an axillary sentinel node biopsy, and 5 patients underwent an axillary lymph node dissection. A subset of cases received adjuvant radiotherapy (n = 2) and chemotherapy (n = 5) after surgery. Endocrine therapy was not given to any of the patients. The details of the surgical approaches and the various therapies are shown in Table 1.
Imaging Techniques From the *Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China; †Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; and ‡Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. Received for publication December 14, 2014; accepted January 29, 2015. Reprints: Wei Jun Peng, MD, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Rd, Xuhui District, Shanghai 200032, China (e‐mail: [email protected]). Contract grant sponsor: This work was supported by the National Natural Science Foundation of China (Grant Nos. 81172073, 30470543, 30670597). The authors declare no conflict of interest. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Mammography and DBT Modalities Eleven patients underwent mammography on 2 units (MAMMOMAT Inspiration; Siemens, Erlangen, Germany [n = 5]; Selenia, Hologic, Boston, MA [n = 6]) where images of mediolateral oblique (MLO) and craniocaudal views were obtained. In addition, 1 patient also underwent DBT (MAMMOMAT Inspiration; Siemens) after mammography. During tomosynthesis imaging, 50 projections were acquired over a 50° angular range (−25° to +25°). These projections were then used to reconstruct tomographic images of the breast with a slice thickness of 1 mm.
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TABLE 1. Data of Clinical Findings
Sex/Age, y
Menopausal Status
1
F/59
Postmenopausal
2 3 4 5
F/59 F/56 F/46 M/78
Postmenopausal Postmenopausal Premenopausal None
6 7 8 9 10
F/50 F/62 F/34 F/50 F/60
Premenopausal Postmenopausal Premenopausal Premenopausal Postmenopausal
11
F/64
Postmenopausal
Patient
Symptoms Palpable mass with pain Palpable mass Palpable mass Palpable mass Palpable mass with pain Palpable mass Palpable mass Palpable mass Without symptoms Palpable mass with pain Palpable mass
Size (cm)
Axillary Management
MRM
1.7
SLNB
No
72
SM Lumpectomy MRM SM
1.2 1.6 5.5 2.0
ALND SLNB ALND SLNB
No No RT and CT CT
45 41 34 32
MRM SM MRM SM Lumpectomy
2.8 2.2 1.0 1.5 1.6
ALND SLNB SLNB ALND SLNB
RT and CT CT No No No
28 24 19 18 15
MRM
2.0
ALND
CT
Surgery
Adjuvant Treatment
Follow-up Time, mo
2
ALND indicates axillary lymph node dissection; CT, chemotherapy; F, female; M, male; MRM, modified radical mastectomy; RT, radiotherapy; SLNB, sentinel lymph node biopsy; SM, simple mastectomy.
Sonography
Image Analysis
All patients were examined via grayscale and color Doppler interrogation to characterize the lesions. The ultrasound machine used was the IU 22 (Philips, Bothell, WA), which is equipped with a 5- to 12-MHz linear array probe. The focus depth was located near the area of interest. The subsequent settings were used: mechanical index, 0.4–0.8; dynamic range, 50–80; and frame rate, 10–20.
The images acquired during mammography, DBT, sonography, and MRI were reviewed until an agreement was reached by 2 experienced mammoradiologists who did not know the pathological diagnosis. All images that were obtained via mammography, DBT, sonography, and MRI were analyzed according to the Breast Imaging Reporting And Data System (BI-RADS 2013, American College of Radiology), which included the following imaging criteria of the lesions: (1) location; (2) shape (eg, round, oval, lobulated, or irregular); (3) size; (4) number; (5) margin (eg, smooth, obscure, irregular, or spiculated); (6) calcification (ie, distribution and appearance); (7) attenuation, echo, and signal intensity; (8) internal enhancement pattern of the mass (eg, homogenous, heterogeneous, rim enhancement, dark internal septations, enhancing internal septations, and central enhancement); and (9) dynamic-enhancement characteristics (eg, persistent curve, plateau curve, and washout curve).
Magnetic Resonance Imaging Nine patients underwent a contrast-enhanced bilateral breast MRI examination in a prone position on different units before surgery. Five examinations were performed with a 3.0-T unit (Signa HDxt; GE Healthcare, Milwaukee, WI), and 4 examinations were performed with a 1.5-T unit (Signa Excite; GE Healthcare), which used a dedicated breast coil (LIBERTY 9000 8-Channel Breast Coil for 1.5-T unit, HD 8-Channel Volume Imaging For Breast Assessment [Vibrant] Breast Array for 3.0-T unit). The unenhanced MRI scan consisted of a localizer sequence, an axial STIR sequence and a T1 fast spin echo (FSE) sequence. The following scan parameters were used: repetition time (TR)/echo time (TE) of 800–900 milliseconds/8.7–10.2 milliseconds for T1weighted imaging (T1WI), TR/TE of 3500–4000 milliseconds/ 80–100 milliseconds for STIR, 2 to 4 excitations, a matrix of 256 256, field of view of 26 26 cm, section thickness of 3 mm, and an intersection gap of 0.6 mm. Gadopentetate dimeglumine (Magnevist; Bayer Schering Pharma, Berlin, Germany) was administered intravenously at a flow rate of 2 mL/s (total dose, 0.2 mmol/kg of body weight) with a highpressure syringe (Dptistar Elite; Liebel-Flarsheim, Cincinnati, OH) and was followed by a 20-mL saline flush. A series of six 1-minute postaxial T1 fat-suppressed enhanced images were acquired with a Vibrant sequence. In addition, delayed highresolution sagittal T1 fat-suppressed enhanced images were also obtained using a sagittal Vibrant sequence. The scan parameters were as follows: TR/TE of 6.2–8.6 milliseconds/3.1–4.0 milliseconds, 1 excitation, matrix of 256 256, field of view of 32 32 cm, section thickness of 2 mm, and intersection gap of 0 mm. Threedimensional Maximum Intensity Projection reconstructions were performed when necessary.
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Pathological Technology All of the pathological specimens were reviewed retrospectively by a pathologist with expertise in breast tumors. All specimens were fixed in 15% buffered formalin and embedded in paraffin. Five-micrometer-thick sections were stained with hematoxylin and eosin after cutting from all tissue samples. Immunohistochemical stains for ACC of the breast were performed in all cases, including stains for ER, PR, Her-2 protein, Ki67, C-kit protein (CD117), cytokeratin (CK) 5/6, CK14, calponin, epithelial membrane antigen, and P63. The pathologist and the 2 radiologists found a correlation between the imaging findings and the pathological findings.
RESULTS Clinical Information Ten patients firstly sought medical help for a palpable mass, and 3 of them presented with accompanying focal pain. One patient was asymptomatic, and the diagnosis of ACC was an incidental finding during a routine health examination. All lesions were solitary and their locations varied: in 5 cases, 3 cases, 2 cases, © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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and 1 case, the lesion was located in the subareolar area, the lower outer quadrant, the upper inner quadrant, and the upper outer quadrant, respectively (Table 2). The median tumor size was 2.1 cm (range, 1.0–5.5 cm) in our series. All patients in our study firstly demonstrated as localized disease and without axillary lymph node metastases. All patients of our study are on follow-up, the time ranged from two months to six years (mean, 30 months). They all underwent diagnostic mammography and sonography every six months, one patient also underwent MRI. All patients had an excellent outcomes, and so far, none of the patients has appeared as a local recurrence or died from complications of her/his disease.
Imaging Characteristics In our study, the sonographic characteristics of ACC of the breast were a hypoechoic solid or heterogeneous mass with a poorly defined border. Echogenic halo and posterior acoustic shadowing were not seen in any of the cases (Figs. 1B, 2B, 3D, and 4B). The margins of masses were not well circumscribed but, rather, were angular (n = 2), indistinct (n = 3), or microlobulated (n = 6). All patients underwent the color Doppler interrogation, and all masses demonstrated minimal vascularity (Figs. 1B, 2B, and 4B). Mammograms were available for all patients, and masses were identified in 9 cases (Figs. 1A, 2A, and 3A). The mass appeared as a lobular or irregular shape with microlobulated, indistinct, or spiculated margins. The male patient presented with an asymmetric dense lesion in the subareolar area (Fig. 4A). One patient with dense breast tissue presented with a palpable mass, but no lesion was identified on mammography. No calcification was found in any case. On the basis of the mammographic
Adenoid Cystic Carcinoma of the Breast
findings, these 10 abnormal cases were considered as BI-RADS category 4 or 5. In addition to conventional mammography, 1 of 11 patients underwent DBT (Fig. 3B). On MRI, 9 masses appeared with a lobulated (n = 3), oval (n = 4), or irregular (n = 2) shape with smooth margins (n = 7) or spiculated (n = 2) margins. Compared with normal glandular tissue, all lesions appeared homogeneously isointense on T1WI (Figs. 1C and 2D). After the injections of contrast agent, the enhancement of all masses was rapid and heterogeneous (n = 4; Fig. 1E) or rapid and homogenous (n = 5; Figs. 2E and 3C). On T2-weighted imaging (T2WI), the larger masses had relatively characteristic findings: 2 of the largest masses (diameter, 5.5 and 2.3 cm) in our series had extensive high T2WI signals and hypointense internal septations (Fig. 1D). These 2 masses demonstrated washout kinetics (Fig. 1G). Significantly, the aforementioned internal septations that were present in the larger masses were enhanced during the delayed phase (Fig. 1F). With regard to the 7 smaller masses, they appeared isointense on T2WI and their internal septations were not enhanced (Figs. 2C, E, and F and 3C). Five cases demonstrated plateau enhancement kinetics (Fig. 2G), and 2 cases demonstrated persistent kinetics. Axillary lymphadenopathy was not observed in any patient who underwent MRI.
Pathological Findings In this study, 11 cases of ACC of the breast were diagnosed. The microscopic manifestation of all specimens revealed the characteristic appearances of ACC in the breast: the epithelial (luminal) and myoepithelial (basaloid) proliferating cells surrounded by pseudocystic spaces were observed in a tumor. Meanwhile, 3 cytoarchitectural patterns were observed such as cribriform,
TABLE 2. Data of Imaging Findings Mammography
Sonography
Patient Location Attenuation Calcification
MRI
Echo
Shape
Margin
Lobulated
Smooth
1
SA
HI
None
Hypoecho
2
UOQ
HI
None
Hypoecho
3
LOQ
Negative
None
Hypoecho
4
LOQ
HI
None
Hypoecho
5 6
SA UIQ
AD HI
None None
Hypoecho Hypoecho
7 8
SA SA
HI HI
None None
Hypoecho Hypoecho
9
UIQ
HI
None
Hypoecho
10
LOQ
HI
None
Hypoecho
11
SA
HI
None
Hypoecho
Signal Intensity
Isointensity on T1WI and T2WI Irregular Smooth Isointensity on T1WI and T2WI Lobulated Smooth Isointensity on T1WI and T2WI Oval Smooth Isointensity on T1WI Hyperintensity on T2WI None None None Irregular Spiculated Isointensity on T1WI Hyperintensity on T2WI None None None Lobulated Smooth Isointensity on T1WI and T2WI Oval Smooth Isointensity on T1WI and T2WI Lobulated Spiculated Isointensity on T1WI and T2WI Oval Smooth Isointensity on T1WI and T2WI
Internal Enhancement
Curve
Rapid and heterogeneous Rapid and homogeneous Rapid and homogeneous Rapid and heterogeneous
Persistent
None Rapid and heterogeneous
None Persistent
None Rapid and homogeneous Rapid and homogeneous Rapid and homogeneous Rapid and heterogeneous
None Plateau
Plateau Plateau Washout
Plateau Plateau Washout
AD indicates asymmetric dense; HI, hyperintense; LOQ, lower outer quadrant; SA, subareolar area; UIQ, upper inner quadrant; UOQ, upper outer quadrant.
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FIGURE 1. A 46-year-old woman with ACC of the right breast. A, An MLO image from a diagnostic mammography shows an irregular mass with a circumscribed margin (arrows) in the subareolar area. B, A sonogram shows an irregular, ill-defined, hypoechoic mass with minimal vascularity on color Doppler interrogation. C, Axial, FSE, T1-weighted MR image of the right breast shows an irregular mass with homogeneous isointensity. D, Axial, STIR, T2-weighted MR image shows an irregular mass with extensive high signal intensity (short arrow) and hypointense internal septations (long arrow). E and F, Axial contrastenhanced MR image with fat saturation illustrates rapid heterogeneous tumor enhancement and enhancement of internal septations in the delayed phase (arrows). G, The mass demonstrated kinetics with a washout pattern. H, 100 magnification of the breast mass shows the cribriform growth pattern, neural invasion, and fibrous septum (arrow). H&E stain. I, 100 magnification of the positive immunohistochemical results for CK14. H&E, hematoxylin and eosin; MR, magnetic resonance. Figure 1 can be viewed online in color at www.jcat.org.
beam-tubular, and solid (Figs. 1H, 2H, 3E, and 4C). CD117 expression showed a significant diffuse membranous pattern in cases of ACC; all cases were positive for CD117 in our study (Figs. 2I and 3F). In addition, CK5/6, CK14 (Figs. 1I and 4D), epithelial membrane antigen, P63, and calponin were focally expressed in patients with ACC. Moreover, staining for ER, PR, and Her-2 protein was performed in all cases. Five cases were negative for the above, but in 2 cases, nuclear positivity for PR was
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observed in scattered neoplastic cells; weak positivity was noted in the cell membrane for Her-2 protein in 3 cases, and only 1 case showed weak staining for these 3.
DISCUSSION Adenoid cystic carcinoma most frequently occurs in the salivary glands, but it also occurs in the breast, lacrimal glands, © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Adenoid Cystic Carcinoma of the Breast
FIGURE 2. A 60-year-old woman with ACC of the right breast. A, An MLO image with an irregular mass and a circumscribed margin (arrows) in the lower outer quadrant. B, A sonogram demonstrates an irregular, well-defined, hypoechoic mass with minimal vascularity on color Doppler interrogation. C, Axial, STIR, T2-weighted MR image of the right breast shows an irregular mass with hypointense internal septations (arrow). D, Axial, FSE, T1-weighted MR image illustrates an irregular mass with homogeneous isointensity. E, Axial contrastenhanced MR image shows rapid homogeneous tumor enhancement and nonenhancement of internal septations in the delayed phase. F, Sagittal contrastenhanced MR image with fat saturation shows nonenhancement of internal septations in the delayed phase. G, This mass demonstrated plateau kinetics. H, 200 magnification of small tumor cells of ACC of the breast that form a solid or tubular growth pattern. H&E stain. I, 200 magnification of positive immunohistochemical results for CD117. H&E, hematoxylin and eosin; MR, magnetic resonance. Figure 2 can be viewed online in color at www.jcat.org.
auditory canal, digestive tract, skin, prostate, and Bartholin glands.12 Adenoid cystic carcinoma of the breast is a particularly rare subtype of malignant breast tumors and accounts for less than 0.1% of all breast carcinomas.2 Although it occurs mainly in women, male patients have been also reported.13,14 In our series, a 78-year-old male patient was diagnosed as having this disease. Although this disease can occur in any age, more cases are diagnosed in women who are 50 or 60 old.15 Consistent with the current
literature, the median age of the 10 female patients in this study was 54 years (range, 34–64 years). Clinically, the mainly symptom is a palpable mass in the breast. Breast pain and nipple retraction are also observed in some patients.16 In our series, 10 patients had a palpable mass, and 3 of them presented with focal pain. Nipple retraction was not observed in any patient. The tumor has been reported to occur mostly in the subareolar area,17 which was consistent with our
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FIGURE 3. A 34-year-old woman with ACC of the right breast. A, An MLO image shows a lobulated mass with spiculated margins (arrow) in the upper inner quadrant. B. An MLO DBT image demonstrates the clearer margin of the mass (arrow). C, Axial contrastenhanced MR image shows rapid homogeneous tumor enhancement and nonenhancement of internal septations in the delayed phase (arrow). D, A sonogram shows a lobulated, ill-defined, hypoechoic mass. E, 200 magnification of islands of cells with a characteristic cribriform pattern and a fibrous desmoplastic background. H&E stain. F, 200 magnification of positive immunohistochemical results for CD117. H&E, hematoxylin and eosin; MR, magnetic resonance. Figure 3 can be viewed online in color at www.jcat.org.
study (5 of 11 cases had tumors in this location). The biological behavior of ACC in the breast and salivary glands is quite different. Perineural invasion is not found in ACC of the breast, but most often observed in ACC of the salivary glands. The prognosis of patients with ACC in the breast and salivary glands is quite
different: the 5-year survival rates ranged from 90% to 100% and 45% to 64%, respectively.18 Histologically, ACC is a tumor composed of luminal and myoepithelial cellular proliferation which surrounded by pseudocystic spaces. Several cytoarchitectural forms have been observed (tubular, cribriform, and solid), and a
FIGURE 4. A 78-year-old man with ACC of left breast. A, An MLO image shows asymmetric density in subareolar area. B. A sonogram shows irregular, ill-defined, hypoechoic mass with minimal vascularity on color Doppler interrogation. C, 100 magnification of the classic cribriform growth pattern of ACC invading the breast parenchyma. H&E stain. D, 100 magnification of positive immunohistochemical results for CK14. H&E, hematoxylin and eosin. Figure 4 can be viewed online in color at www.jcat.org.
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mixture of them is commonly observed.19 Immunohistochemical studies have shown that ACC of the breast has a characteristic phenotype that is negative for ER, PR, and Her-2 proteins and positive for c-KIT protein.20In our series, 5 lesions were triple negative, 3 lesions were weakly positive for PR, 2 lesions were weakly positive for Her-2 protein, and 1 lesion was weakly positive for all of them. Unlike the poor prognosis that is associated with other triple-negative breast cancers, ACC has been reported to have an excellent survival rate despite its malignant nature.21 Distant metastases and involvement of the axillary nodes are very rare, which is in accordance with our study. Arpino et al22 found that a minority of patients had distant metastases and deaths (7.6% and 3.3%, respectively). In our study, all patients have favorable outcome, and so far, every patient is alive without any complication. The ACC of the breast has been described as a hypoechoic and heterogeneous mass with unsharp margins, which is consistent with our study.10,11,23 All of the tumors in our series demonstrated color Doppler interrogation with minimal peripheral color flow. It has been described as a benign-appearing smooth, lobulated, or an irregular mass on mammography,8–10,23 which is also consistent with what was observed in our study. One patient in our series had a tangible mass, but no lesion was observed on mammography; this might have been caused by the highly dense breast tissue that covered the mass. To our knowledge, the manifestation of ACC of the breast is controversial on MRI. Some scholars24,25 have described it as a round, oval, or irregular lesion with rapid enhancement (no washout) that extends from the margin to the center over time.8 Unlike the former, Glazebrook et al23found that on MRI, the masses appeared as irregular shapes with spiculated margins. Unenhanced scans showed that 2 of the largest masses demonstrated extensive hyperintensity on T2WI and that the 2 smaller masses demonstrated isointensity on T2WI. In addition, enhanced scans showed suspicious malignant enhancement. Compared with the findings of Glazebrook et al, only one sign was consistent with ours: the larger mass with extensive T2WI hyperintensity and the smaller mass with T2WI isointensity. In contrast to the findings of Glazebrook et al, most of our cases presented with benignappearing lesions (4 of 9 had oval shapes, and 7 of 9 had smooth margins). Moreover, we found that all masses had internal septations with low signal on T2WI and that the internal septations in the larger masses were enhanced in the delayed phase. We speculated that the internal septations observed on T2WI may correspond to the stroma embedded within the tumor islands (Fig 1I). Imaging findings may help to distinguish ACC of the breast from infiltrating ductal carcinoma (IDC) and fibroadenoma of the breast. Most cases of ACC of the breast have well-defined margins, whereas most cases of IDC have spiculated or irregular margins. On T2WI, the larger lesions of ACC of the breast demonstrated an extensive high signal, whereas IDC and fibroadenoma appeared as hypointense or isointense in most cases. Some fibroadenoma may overlap ACC, especially in small lesions, they both have benign imaging manifestations. However, the larger lesions of ACC usually have obvious heterogeneous high T2WI signals whereas the signals of fibroadenoma are homogeneous in most cases. Furthermore, some fibroadenomas have non-enhancing internal septations, while the internal septations of ACC have been described as delay-enhanced, especially in the larger lesions. Overall, ACC is a rare type of breast cancer, We described some relative useful imaging manifestations to help to make the diagnosis. However, in some really overlapped lesions, the core biopsy is needed.25 Our study had several limitations. A predominant limitation was the small sample size owing to the scarcity of the tumors that
Adenoid Cystic Carcinoma of the Breast
formed the basis of the imaging review. This resulted in a lack of statistical significance. Another limitation was a lack of consistent imaging parameters due to the length and the depth of time when the cases were collected. In addition, some of the imaging findings were nonspecific. Nevertheless, we consider that some valuable manifestations emerged on MRI: most lesions of ACC in the breast are well defined; on T2WI, the larger ACCs of the breast might show extensive high signal and hypointense internal septations, which could enhance in the delayed phase. REFERENCES 1. Sarnaik AA, Meade T, King J, et al. Adenoid cystic carcinoma of the breast: a review of a single institution's experience. Breast J. 2010;16:208–210. 2. Kulkarni N, Pezzi CM, Greif JM, et al. Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base. Ann Surg Oncol. 2013;20:2236–2241. 3. Vranic S, Bender R, Palazzo J, et al. A review of adenoid cystic carcinoma of the breast with emphasis on its molecular and genetic characteristics. Hum Pathol. 2013;44:301–309. 4. Persson M, Andren Y, Mark J, et al. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A. 2009;106:18740–18744. 5. Soon SR, Yong WS, Ho GH, et al. Adenoid cystic breast carcinoma: a salivary gland-type tumour with excellent prognosis and implications for management. Pathology. 2008;40:413–415. 6. Boujelbene N, Khabir A, Boujelbene N, et al. Clinical review—breast adenoid cystic carcinoma. Breast. 2012;21:124–127. 7. Kim M, Lee DW, Im J, et al. Adenoid cystic carcinoma of the breast: a case series of six patients and literature review. Cancer Res Treat. 2014; 46:93–97. 8. Okamoto Y, Sumiyama Y, Arima Y, et al. A case of adenoid cystic carcinoma (ACC) of the breast and review of the utility of preoperative imaging diagnose. Breast Cancer. 2001;8:84–89. 9. Santamaria G, Velasco M, Zanon G, et al. Adenoid cystic carcinoma of the breast: mammographic appearance and pathologic correlation. Am J Roentgenol. 1998;171:1679–1683. 10. Sperber F, Blank A, Metser U. Adenoid cystic carcinoma of the breast: mammographic, sonographic, and pathological correlation. Breast J. 2002;8:53–54. 11. Dinkel HP, Clees M, Gassel AM. Role of sonography in detecting recurrence in adenoid cystic carcinoma of the breast. Am J Roentgenol. 1999;173:497–498. 12. Xue Y, Liu X, Poplack S, Memoli VA. Adenoid cystic carcinoma of the breast in reduction mammoplasty. Breast J. 2012;18:611–613. 13. Kshirsagar AY, Wader JV, Langade YB, et al. Adenoid cystic carcinoma of the male breast. Int Surg. 2006;91:234–236. 14. Yoo SJ, Lee DS, Oh HS, et al. Male breast adenoid cystic carcinoma. Case Rep Oncol. 2013;6:514–519. 15. Bhosale SJ, Kshirsagar AY, Patil RK, et al. Adenoid cystic carcinoma of female breast: a case report. Int J Surg Case Rep. 2013;4:480–482. 16. Silva I, Tome V, Oliveira J. Adenoid cystic carcinoma of the breast with cerebral metastisation: a clinical novelty. BMJ Case Rep. 2011. doi: 10.1136/bcr.08.2011.4692. 17. Torrao MM, da Costa JM, Ferreira E, et al. Adenoid cystic carcinoma of the breast. Breast J. 2007;13:206. 18. Marchio C, Weigelt B, Reis-Filho JS. Adenoid cystic carcinomas of the breast and salivary glands (or ‘The strange case of Dr Jekyll and Mr Hyde’ of exocrine gland carcinomas). J Clin Pathol. 2010;63:220–228. 19. Defaud-Henon F, Tunon-de-Lara C, Fournier M, et al. Adenoid cystic carcinoma of the breast: clinical, histological and immunohistochemical characterization. Ann Pathol. 2010;30:7–16.
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20. Cadoo KA, McArdle O, O'Shea AM, et al. Management of unusual histological types of breast cancer. Oncologist. 2012;17:1135–1145.
23. Glazebrook KN, Reynolds C, Smith RL, et al. Adenoid cystic carcinoma of the breast. Am J Roentgenol. 2010;194:1391–1396.
21. Ghabach B, Anderson WF, Curtis RE, et al. Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study. Breast Cancer Res. 2010;12:R54.
24. Tsuboi N, Ogawa Y, Inomata T, et al. Dynamic MR appearance of adenoid cystic carcinoma of the breast in a 67-year-old female. Radiat Med. 1998;16:225–228.
22. Arpino G, Clark GM, Mohsin S, et al. Adenoid cystic carcinoma of the breast: molecular markers, treatment, and clinical outcome. Cancer. 2002; 94:2119–2127.
25. Kasagawa T, Suzuki M, Doki T, et al. Two cases of adenoid cystic carcinoma: preoperative cytological findings were useful in determining treatment strategy. Breast Cancer. 2006;13:112–116.
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© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
