Certain subtypes of breast cancer can be particularly challenging to detect on routine mammography. This can have implications for staging and surgical outcomes.¹ Although the use of supplemental imaging tools, such as ultrasound and MRI, help to improve cancer detection and delineation of the extent of disease,² cancers such as invasive lobular carcinoma (ILC) and ductal carcinoma in situ (DCIS) continue to be problematic. Other generally readily detected carcinomas, such as medullary, papillary, and mucinous (colloid), may be difficult to recognize as malignant because of their propensity for relatively benign-appearing morphologic features.

Although ILC represents only about 10% of all breast tumors,³ it is known to be one of the most common reasons for a false-negative mammogram.⁴ The infiltrating growth pattern of single-file strands of malignant cells, often with minimal fibrotic reaction, is one of the reasons that ILC can be difficult to detect (Figure 1). In addition, if an ILC does produce a mammographically detectable finding, it may not form a mass and may be of relatively low or equal density to normal fibroglandular tissue.³ Even large lesions may still be occult on mammography.⁵ Mammographic sensitivity for ILC ranges between 57% and 89%.^4–8 In addition, ILC has a higher propensity for multifocal and bilateral involvement. Its extent is often underestimated by mammography.⁹,¹⁰ Understaging can significantly affect surgical outcomes and patient treatment. MRI has been shown to be useful in better defining the extent of disease in patients with ILC.¹⁰,¹¹

FIGURE 1 A and B (close up): H&E stains of an invasive lobular carcinoma demonstrating the classic single-file pattern of malignant cells extending into normal parenchyma (arrows).

The increasing use of screening mammography has led to an increase in the detection of DCIS, usually presenting as clustered microcalcifications. However, establishing the extent of disease can be problematic because DCIS is commonly multifocal and is often noncalcified. A recent study suggested that MRI may be more useful in detecting DCIS than previously thought.¹²

Mucinous carcinoma, also termed colloid carcinoma, is relatively uncommon.¹³ Because it often presents as a circumscribed mass, it may potentially be misinterpreted as a benign lesion, such as a fibroadenoma. However, close inspection usually reveals features that should distinguish mucinous carcinoma from benign entities, such as marginal irregularity or heterogeneous echotexture on ultrasound. In a similar manner, medullary carcinoma can present as a well-circumscribed mass. Medullary carcinomas account for about 3% to 5% of breast cancers and have a prognosis that is generally better than more common types of invasive breast cancer.

Another problematic breast cancer is papillary carcinoma, which can also present as a wellcircumscribed mass on mammography. Ultrasound usually reveals an intraductal or intracystic mass. However, because papillary carcinoma cannot generally be differentiated on the basis of imaging from the more common benign papilloma, biopsy is required for all complex breast masses.

Some carcinomas may have features on ultrasound that could be confused with benign entities. Purely hyperechoic lesions on ultrasound, such as a lipoma, are invariably benign. However, some invasive carcinomas may have a hyperechoic halo that may simulate a benign lesion. On close inspection, a hypoechoic “nidus” or central region is generally present to distinguish carcinomas from completely hyperechoic benign lesions. Some carcinomas, particularly high-grade cancers and metastatic lymph nodes, may be extremely hypoechoic on ultrasound and could be mistaken for anechoic cysts. In addition to proper gain settings and margin analysis, color Doppler helps in distinguishing solid masses from cysts (Figure 2).

FIGURE 2 A, Ultrasound of an extremely hypoechoic right breast axillary tail lesion (arrow). B, Color Doppler evaluation demonstrates internal vascularity within the lesion, indicating it is solid and thereby excluding a cyst (arrow). Biopsy proved this to be a metastatic lymph node.

Coexisting medical conditions, such as infection, trauma, and lactational changes, may hinder the detection and diagnosis of breast cancer. In addition, inflammatory breast cancer can be difficult to distinguish from benign infection process (mastitis). Careful correlation of the clinical history and physical examination findings should be made with the imaging findings. In some cases, distinguishing between benign and malignant may not be possible solely based on imaging features.

A 50-year-old woman was found on screening mammography to have suspicious pleomorphic microcalcifications in the 12-o’clock position of the right breast (Figure 1). Biopsy was performed with stereotactic technique, confirming intermediate-grade ductal carcinoma in situ (DCIS) (Figure 2). There was a family history of breast cancer, most notably in a sister at age 31.

FIGURE 1 Mediolateral (A) and cranial-caudal (CC) (B) magnification views of the 12-o’clock position of the right breast show highly suspicious, clustered, pleomorphic microcalcifications. Many of the calcifications are linear, casting forms.

FIGURE 2 Specimen radiograph from the stereotactic biopsy confirms that the calcifications were successfully sampled and provides an unobstructed second look at the morphology of the microcalcifications. They vary in size and shape, and several of the linear forms vary in density.

Breast MRI was obtained to evaluate for occult invasive components and extent of disease. Ultrasound had not shown an associated mass. The breast MRI showed clumped, small masses of intense enhancement with washout at the expected level of the residual known DCIS (Figures 3 and 4). There was a second, separate site of concerning, clumped enhancement in the same breast, with plateauing enhancement, thought suspicious for possible additional, noncalcified DCIS. MRI-guided biopsy was performed, and pathology showed two tiny foci of high-grade DCIS, the largest 1 mm in size. A clip was placed to mark the MRI-guided biopsy site, and postbiopsy mammography confirmed it to be removed in location from the remaining microcalcifications (Figure 5).

FIGURE 3 Axial enhanced, subtracted images from above to below. A, Rim enhancement outlines the clip placed during stereotactic biopsy. Presumably, the large-gauge (8-gauge) biopsy incited a reaction, which surrounds the collagen plug type clip. B, Just below the level of the clip, adjacent small enhancing masses are seen, which appear to correspond to the location of the residual microcalcifications. C, At a lower level, there is a regional grouping of small foci of enhancement that enhance more than other regions of the breast.

FIGURE 4 Sagittal, enhanced, subtracted breast MR images, from medial to lateral. A, An oblong void in the 12-o’clock position is outlined by a thin enhancing rim and corresponds to the clip placed at stereotactic biopsy. Enhancement at the inferior aspect of the clip corresponds in location to the known residual DCIS (microcalcifications remaining in the breast after stereotactic biopsy). B, An adjacent section, lateral to the clip, shows clumped additional enhancement and corresponds to the known residual DCIS. C, A more lateral section shows more posterior clumped enhancement, not directly contiguous with the known, calcified DCIS. D, Analysis [region of interest (1) and kinetic curve (2)] of the enhancement curve of the known residual DCIS shows washout, indicating angiogenesis. E, A plateauing pattern of less intense enhancement is seen at the level of the suspected noncalcified DCIS [region of interest (1) and kinetic curve (2)].

FIGURE 5 Lateral (A) and CC (B) digital mammograms obtained after MRI-guided biopsy of the suspected noncalcified DCIS show the clip to be in the posterior upper outer quadrant. The clip placed at the time of stereotactic biopsy is more anterior, at 12 o’clock (arrows), and projects at least 4 cm away.

These evaluations showed the patient had proven multicentric DCIS, including noncalcified DCIS. She was recommended to have a mastectomy but was strongly desirous of breast conservation. Accordingly, lumpectomies were performed after a triple-needle localization, in which the remaining microcalcifications at 12 o’clock were bracketed with two needles (Figure 6), and the clip at 9 to 10 o’clock from the MRI-guided biopsy was separately localized (Figure 7). The specimen at 12 o’clock contained both of the bracketing localization wires and the remaining pleomorphic microcalcifications. These were noted to approach a margin, from which additional tissue was obtained. The initial specimen from the 9- to 10-o’clock localization showed the hook wire, but not the MRI-placed clip. The surgeon was advised of this, additional tissue was obtained and radiographed, and the clip was found in the second specimen (Figure 8).

FIGURE 6 Needle localization of the calcified residual DCIS at 12 o’clock was accomplished by placement of two bracketing wires. The specimen radiograph shows the two hook wires, as well as the remaining microcalcifications, which approach a margin. The beaded appearance of an irregular linear casting calcification is well demonstrated here. The clip (collagen plug–type) is seen on one edge of the specimen as well.

FIGURE 7 The initial specimen from the localization of the MRI-placed clip showed the hook wire, but not the clip.

FIGURE 8 An additional specimen obtained after the surgeon was informed of the above shows the MRI-placed clip.

The pathology of the 12-o’clock specimen showed a 2.7-cm region of high-grade DCIS, with extension into lobules and with close lateral, inferior, and deep margins. The specimen from 9 o’clock showed atypical ductal hyperplasia (ADH), with no residual DCIS and biopsy site changes.

Mastectomy was again recommended for this patient, who desired re-excision and breast conservation. The 12-o’clock lumpectomy site was re-excised. The re-excised lateral margin showed three microscopic foci of high-grade DCIS (largest, 0.5 cm), two of which were closer than 2 mm to the new lateral margin. The new inferior margin was clear, and this specimen showed a single microscopic focus of DCIS. The additional deep margin excision showed three foci of invasive ductal carcinoma (IDC) (largest, 0.4 cm), with multifocal high-grade DCIS involving greater than 50% of the lesion (extensive intraductal component), DCIS focally at the new deep margin, and multiple foci of DCIS and IDC closer than 2 mm to the new deep margin.

Mastectomy was again recommended for this patient, who strongly desired re-excision and breast conservation. Re-excision of the lateral, inferior, and deep margins was performed. The specimens showed a single duct with high-grade DCIS and an additional focus of ADH in the lateral margin specimen, but the new margins were clear.

A 51-year-old woman underwent breast imaging evaluation for a clear right nipple discharge. Two years before, she was diagnosed with right breast intracystic papillary neoplasm, estrogen receptor positive (Figure 1), and treated with lumpectomy only. On physical examination, a serous fluid discharge could be readily elicited by palpation of the right lateral breast, in the region of her surgical scar. No clear imaging correlate could be identified on diagnostic mammography or breast ultrasound, with scarring noted on ultrasound at the lumpectomy site (Figure 2). Breast MRI was obtained and showed an unusual focus of branched, linear right retroareolar enhancement, with washout (Figures 3 and 4). A second focus of abnormal mass enhancement measuring 8 mm was identified, at the 9-o’clock right breast posterolateral level, with washout (Figure 5). MRI-guided biopsy was performed of the retroareolar branched enhancement, identifying intracystic papillary carcinoma, considered in situ, with no invasion identified. The second site was too posterior to reach with a grid MRI-localizing device. A second breast ultrasound was performed to find a correlate for the posterior MRI abnormality (Figure 6). A 6-mm hypoechoic nodule was identified on ultrasound at 10 o’clock, thought to be the probable correlate for the MRI finding. This had not been noted on a prior right breast ultrasound, obtained before the MRI. Ultrasound-guided core needle biopsy identified low-grade, cribriform ductal carcinoma in situ (DCIS), similar in histology to the patient’s prior specimens.

FIGURE 1 Ultrasound of the patient’s original lesion, in the right breast at 9 o’clock, shows a complex, solid, and partially cystic mass. The cystic component yielded bloody fluid and contains a mural nodule. Vacuum-assisted core biopsy of the solid component identified intracystic papillary carcinoma (IPC), considered in situ and not invasive.

FIGURE 2 Ultrasound of the right lumpectomy site shows a complex branching linear scar, extending close to the skin surface.

FIGURE 3 A V-shaped branched linear focus of enhancement, which could be ductular, is seen in the retroareolar right breast on enhanced, subtracted axial MRI. Biopsy with MRI guidance obtained IPC.

FIGURE 4 Analysis of the kinetic data with the aid of DynaCAD software. A, Kinetic information is color coded and overlain on breast MRI. A region of interest has been placed in the focus of branched enhancement. B, Graph of the enhancement (change in signal intensity versus time) shows a washout pattern: rapid early upstroke and subsequent decline.

FIGURE 5 Enhanced, subtracted axial breast MRI shows a second indeterminate finding in the right lateral breast at 9 o’clock: an 8-mm mass with washout. A lymph node was considered in the differential. It could not be reached for performance of MRI-guided biopsy in the same procedure.

FIGURE 6 Targeted, second-look ultrasound of the right lateral breast identifies a 6-mm indeterminate, solid-appearing nodule with adjacent vascularity. Biopsy identified low-grade, cribriform DCIS, similar in histology to the patient’s prior specimens.

With two proven sites of right breast intracystic papillary carcinoma (IPC)/DCIS, the patient was treated with modified radical mastectomy. She elected to undergo prophylactic mastectomy on the left at the same time, with immediate reconstruction with tissue expanders. On the right, one sentinel and one additional lymph node were negative. The right mastectomy specimen showed focal residual intracystic papillary carcinoma and focal low-grade micropapillary DCIS at the subareolar level. The left prophylactic mastectomy specimen was negative.

An additional example of this less common histology is illustrated in Figure 7.

FIGURE 7 Another case of low-grade IPC, without invasion, in an 83-year-old woman who developed a new retroareolar mass, initially noted on mammography. Ultrasound of the mass shows it to be solid and vascular, with small cyst-like spaces within it and microlobulated borders. There is enhanced through-transmission.

A 46-year-old woman, with a known left breast sarcoma history, underwent preoperative bilateral MRI. The MRI demonstrated a previously unknown mass in the contralateral breast (Figures 1, 2, 3, and 4). Ultrasound identified a solid corresponding mass in the lower outer right breast (Figure 5). Ultrasound-guided core needle biopsy diagnosed an invasive mucinous carcinoma. The patient was treated with bilateral lumpectomies and radiation therapy.

FIGURE 1 Five-minute postcontrast subtracted axial MRI demonstrates an enhancing 1.6-cm mass in the lower outer right breast (arrow). The mass has partially circumscribed and partially irregular margins. In addition, the internal enhancement pattern is heterogeneous, with rim enhancement.

FIGURE 2 Fat-saturated T2-weighted spin-echo image of the right breast. The mass in the lower outer right breast demonstrates high T2 signal.

FIGURE 3 MRI with CAD kinetic color overlay. The mass in the lower outer right breast is seen to have a uniform kinetic pattern as demonstrated by the blue color overlay. The blue color indicates a type I (progressive) or benign enhancement pattern.

FIGURE 4 Quantitative analysis demonstrates the enhancement kinetics of the mass. There is rapid uptake and progressive enhancement pattern.

FIGURE 5 Ultrasound image of the lower outer right breast demonstrates a hypoechoic solid mass (arrow) corresponding to the mass seen on MRI. The mass has a mildly heterogeneous internal echotexture and microlobularity of anterior margins. There is increased acoustic through-transmission.

TEACHING POINTS

This case is an example of a mucinous carcinoma, also termed colloid carcinoma, which consists of tumor cells floating within pools of mucin. On imaging, mucinous carcinomas potentially can be misinterpreted as benign. Features suggestive of benignity illustrated by this lesion include relatively well circumscribed margins, high T2 signal on MRI, and posterior acoustic through-transmission on ultrasound. However, detailed examination helps to prevent confusing this lesion for a fibroadenoma. Close inspection of both the MRI and the ultrasound shows that the margins of the mass are not as well circumscribed as expected for a fibroadenoma. In addition, unlike classic fibroadenomas, the internal architecture of this mucinous carcinoma is heterogeneous on both the MRI and ultrasound. Mammographically, mucinous carcinomas often present as wellcircumscribed, relatively low-density masses, which may delay their diagnosis. Pure mucinous carcinoma is an uncommon form of breast malignancy, accounting for 1% to 2% of all breast cancers. They tend to occur in older patients. In contrast to mixed mucinous carcinomas, pure mucinous carcinomas have a favorable prognosis, are often low-grade tumors, and rarely metastasize.

Not every colloid carcinoma is as innocent in appearance as this example. Another case of an invasive mucinous carcinoma, in a 72-year-old woman with a palpable right breast mass, also shows bright signal on T2-weighted MRI, but other features of malignancy are notable (Figures 6, 7, 8, and 9).

FIGURE 6 Five-minute postcontrast subtracted axial MRI demonstrates a rim-enhancing, 1.7-cm mass in the central right breast (arrow). The mass demonstrates irregular margins.

FIGURE 7 Delayed postcontrast image. The mass in the central right breast displays heterogeneous rim enhancement and enhancing septa, with areas of contrast washout.

FIGURE 8 MR T2-weighted spin-echo image of the right breast. The mass demonstrates high T2 signal intensity.

FIGURE 9 Ultrasound image of the central right breast demonstrates a hypoechoic solid mass corresponding to the mass seen on MRI. The mass has irregular and angular margins.