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Unusual Breast Cancers: Useful Clues to Expanding the Differential Diagnosis¹

¹ From the Department of Radiology, University of Virginia, Box 800170, Charlottesville, VA 22908. Received October 3, 2005; revision requested November 14; revision received December 19; accepted January 23, 2006; final version accepted April 3; final review and update by the author August 25. Address correspondence to the author (e-mail: jah7w{at}virginia.edu).

	ABSTRACT

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

 
Invasive ductal carcinoma and ductal carcinoma in situ account for about 85% of breast cancers. Unusual breast neoplasms may be broadly divided into invasive lobular carcinoma, well-differentiated subtypes of invasive ductal carcinoma, cancers of stromal origin, and metastatic neoplasms. Clues are often present in imaging characteristics, patient demographics, and/or clinical features that may suggest that the finding is not the usual type of breast cancer. Some rare malignancies also provide specific clues to their diagnosis. This review provides an overview of unusual and a few rare malignant breast neoplasms, highlighting particular or specific clinical or imaging findings that will enable residents to expand their differential diagnosis of breast lesions beyond invasive ductal carcinoma.

© RSNA, 2007

	INTRODUCTION

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

 
Invasive ductal carcinoma (IDC) not otherwise specified and ductal carcinoma in situ (DCIS) account for 85% of breast cancers (1). IDC not otherwise specified typically manifests as a spiculated or irregular mass or as a new focal asymmetry, while DCIS typically manifests as a cluster of pleomorphic or fine linear-branching calcifications. The remaining 15% of breast cancers are other types of malignant neoplasm.

Unusual breast cancers may be broadly divided into invasive lobular carcinoma (ILC), well-differentiated subtypes of IDC, cancers of stromal origin, and metastatic neoplasms. Clues are often present in the imaging characteristics, patient demographics, or clinical features that may suggest that the finding is not a typical breast cancer. Some rare malignancies also provide similar clues to the diagnosis.

This review will provide an overview of unusual, as well as a few rare, malignant breast neoplasms, highlighting particular or specific clinical or imaging findings that will enable residents to expand their differential diagnoses of breast lesions beyond IDC.

	INVASIVE LOBULAR CARCINOMA

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

 
ILC accounts for 6%–9% of breast cancers (1,2). While IDC tends to enlarge en masse (like an expanding balloon), ILC spreads as sheets of a single-cell layer along Cooper ligaments and other structures in the breast (Fig 1), somewhat like a spiderweb. Because of this infiltrative growth pattern, ILC is more difficult to detect at clinical examination and mammography than is IDC (3,4). ILC is therefore usually larger at diagnosis than IDC (5) and is often multifocal (2). Lymph node metastasis is less common with ILC than IDC for equal-size lesions, however (5), so the stage at diagnosis for ILC is overall similar to that for IDC despite the larger size at diagnosis (6).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 1a: (a) Left craniocaudal (left) and mediolateral oblique (MLO) (right) mammographic views in 48-year-old woman with a palpable lump at 12-o'clock position (triangular marker) show focal asymmetry (circled area) in the region of the palpable abnormality, with subtle architectural distortion (arrows) on MLO view. (b) Ultrasonographic (US) scan shows a poorly defined area of architectural distortion and several hypoechoic areas (arrowheads) with posterior acoustic shadowing (straight arrows) without a discrete mass. Architectural distortion can be recognized as abrupt termination of normal Cooper ligaments (curved arrows). (c) Histologic section shows ILC with sheets of cells of single-layer thickness (arrows) infiltrating through fibrous stroma, which is stained pink. (Hematoxyllin-eosin stain; original magnification, x200.)

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 1b: (a) Left craniocaudal (left) and mediolateral oblique (MLO) (right) mammographic views in 48-year-old woman with a palpable lump at 12-o'clock position (triangular marker) show focal asymmetry (circled area) in the region of the palpable abnormality, with subtle architectural distortion (arrows) on MLO view. (b) Ultrasonographic (US) scan shows a poorly defined area of architectural distortion and several hypoechoic areas (arrowheads) with posterior acoustic shadowing (straight arrows) without a discrete mass. Architectural distortion can be recognized as abrupt termination of normal Cooper ligaments (curved arrows). (c) Histologic section shows ILC with sheets of cells of single-layer thickness (arrows) infiltrating through fibrous stroma, which is stained pink. (Hematoxyllin-eosin stain; original magnification, x200.)

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 1c: (a) Left craniocaudal (left) and mediolateral oblique (MLO) (right) mammographic views in 48-year-old woman with a palpable lump at 12-o'clock position (triangular marker) show focal asymmetry (circled area) in the region of the palpable abnormality, with subtle architectural distortion (arrows) on MLO view. (b) Ultrasonographic (US) scan shows a poorly defined area of architectural distortion and several hypoechoic areas (arrowheads) with posterior acoustic shadowing (straight arrows) without a discrete mass. Architectural distortion can be recognized as abrupt termination of normal Cooper ligaments (curved arrows). (c) Histologic section shows ILC with sheets of cells of single-layer thickness (arrows) infiltrating through fibrous stroma, which is stained pink. (Hematoxyllin-eosin stain; original magnification, x200.)

Now imagine what a spiderweb in the breast might look like on a mammogram: a lot of straight lines, a little denser in the middle, but little or no central mass. The most frequent manifestation of ILC is indeed architectural distortion with or without a central mass (10) or a focal asymmetry (6) (Fig 1). Calcifications are a very uncommon feature of ILC (6,10). Unlike IDC, ILC is more frequently seen in only one view, most commonly in the craniocaudal view (6), which typically has better compression than the MLO view. Recall the similarity of ILC to a spiderweb; greater compression of the breast in the craniocaudal projection would make the straight lines become more obvious. Mammography often greatly underestimates the size of ILC as seen at histologic examination (5), which makes sense because only the areas most affected with the infiltrative sheets of tumor cells are likely to be evident at imaging.

When ILC is large, the affected breast may appear to be decreasing in size on the mammogram (Fig 2); this has been termed the "shrinking breast" (11). Such shrinkage is probably due to the sheets of tumor cells causing decreased compressibility of the breast so that the breast tissue does not spread out as well during mammographic compression, making the breast appear smaller on the mammogram. Note that the shrinking breast is a mammographic and not a clinical finding of ILC. The physical size of the breast at clinical inspection is not different, though the patient may note thickening or a palpable lump on the affected side.

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 2a: Mammograms in 77-year-old woman who stated that her right breast was becoming firmer. Craniocaudal views of both breasts from (a) previous and (b) current year show an apparent decrease in size of the right breast (arrows). Patient exhibited no physical change in breast size at clinical examination. At mastectomy, all quadrants were involved with ILC.

View larger version (87K): [in this window] [in a new window] [Download PPT slide]   Figure 2b: Mammograms in 77-year-old woman who stated that her right breast was becoming firmer. Craniocaudal views of both breasts from (a) previous and (b) current year show an apparent decrease in size of the right breast (arrows). Patient exhibited no physical change in breast size at clinical examination. At mastectomy, all quadrants were involved with ILC.

Management of a lesion manifesting as architectural distortion without a central mass is controversial, since the differential diagnosis includes radial sclerosing lesion (radial scar). Surgical excision is often recommended rather than core biopsy since 7%–30% of radial sclerosing lesions may be associated with small foci of IDC or DCIS (12). However, 29% of lesions suspected of being radial sclerosing lesions at imaging are actually carcinomas at biopsy (13). Core biopsy prior to excision is therefore often helpful in surgical planning.

At my institution, we discuss with the patient the differential diagnosis of radial sclerosing lesion versus ILC at the time of diagnostic imaging. We advise patients that they will ultimately need surgical excision but that core biopsy may aid surgical planning. The patients are given appointments for needle biopsy and for breast surgery consultation several days after the biopsy. If core biopsy results show invasive carcinoma, appropriate management that includes sentinel node biopsy and wide surgical excision can be planned. If core biopsy results are benign or show a radial sclerosing lesion, surgical excision of a small volume of tissue for diagnostic purposes is performed. Patients are very receptive to this plan as long as they understand that two procedures (core biopsy and surgical excision) are being recommended at the outset. Surgical colleagues at our institution prefer to have core biopsy information prior to proceeding to the operating room.

Other investigators are evaluating if follow-up rather than excisional biopsy is acceptable when core biopsy results show a radial sclerosing lesion in selected patients. A study by Brenner et al (14) found no cancers at excision when radial sclerosing lesion was diagnosed at stereotactic core biopsy by using an 11-gauge vacuum-assisted biopsy device, and no atypia was present at histologic examination. Close-interval follow-up may be a reasonable alternative to excision when radial sclerosing lesions are diagnosed with this method.

Fine-needle aspiration biopsy is not as sensitive for ILC as it is for IDC (15). Core biopsy is the preferred method when ILC is suspected, even when the lesion is palpable (15). It is likely more difficult to obtain adequate cellular material from ILC because of the infiltrative pattern of spread with single-layer sheets of cells. Imagine trying to shear off a piece of a spiderweb with a small needle. It would be far easier to remove small pieces at core biopsy.

ILC is more frequently associated with positive margins at excision (16) and is more frequently treated with mastectomy (5). This is likely due to the large size of ILC at diagnosis and the underestimation of the disease extent at conventional imaging. If breast conservation is desired by the patient, US or magnetic resonance (MR) imaging may be useful for assessing the extent of the disease (4,17). In 39% of women with ILC, MR imaging depicts more extensive disease than is suspected with conventional imaging (17). On MR images, ILC may manifest as an enhancing solitary mass with irregular margins, multiple enhancing lesions, or only enhancing septa (18).

In summary, ILC typically infiltrates with single-layer-thick sheets of cells like a spiderweb rather than en masse. ILC should be considered in the differential diagnosis of lesions that manifest primarily as architectural distortion with or without a central mass when vague hypoechoic areas with posterior acoustic shadowing are seen at US, when the breast appears to have decreased in size on a mammogram (shrinking breast), and when the clinical examination findings are more suspicious than the imaging findings.

	SUBTYPES OF DUCTAL CARCINOMA

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

 
Most breast cancers are of ductal origin, with IDC not otherwise specified being the most common type. "Not otherwise specified" refers to the lack of differentiation of the cancer. Several subtypes of ductal carcinoma, however, exhibit differentiation by producing tubules, mucin, et cetera. These subtypes of ductal carcinoma are named according to the morphologic differentiating feature. Because these cancers are well differentiated, they grow slowly (with the exception of medullary carcinoma) and are often relatively circumscribed at imaging (with the exception of tubular carcinoma). These well-differentiated tumors will nearly always be grade I of III (modified Scharff Bloom Richardson scale) and, therefore, have an excellent prognosis. If the tumor type is mixed with less than 90% of the differentiated subtype, prognosis is determined by the least differentiated portion of the tumor.

Tubular Carcinoma
Tubular carcinoma accounts for about 1% of breast cancers (1,19). It is often found incidentally at screening rather than manifesting with clinical findings (20). The appearance mimics typical IDC not otherwise specified, manifesting as one or more small spiculated masses (Fig 3) (21). The spicules are often longer than the central mass (21). On US scans, the appearance also mimics IDC not otherwise specified, manifesting as a hypoechoic solid mass with ill-defined margins and posterior acoustic shadowing (21).

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 3a: Mammograms in 42-year-old woman with palpable mass in the right breast. (a) Right craniocaudal view shows architectural distortion (circled area). Triangular marker (arrow) on patient's skin marks the palpable abnormality, which corresponds to a simple cyst on US scan (not shown). (b) Craniocaudal spot compression view of right breast shows a small spiculated mass (arrow). Core needle biopsy revealed invasive tubular carcinoma.

View larger version (90K): [in this window] [in a new window] [Download PPT slide]   Figure 3b: Mammograms in 42-year-old woman with palpable mass in the right breast. (a) Right craniocaudal view shows architectural distortion (circled area). Triangular marker (arrow) on patient's skin marks the palpable abnormality, which corresponds to a simple cyst on US scan (not shown). (b) Craniocaudal spot compression view of right breast shows a small spiculated mass (arrow). Core needle biopsy revealed invasive tubular carcinoma.

Tubular carcinoma may occasionally be difficult to differentiate from radial sclerosing lesion (radial scar) at histologic examination. If this is of question, particularly at core biopsy, —smooth muscle actin stain or maspin stain may be used to help identify myoepithelial cells in the basement membrane of normal tissue, but staining will be absent in tubular carcinoma (24). Tubular carcinoma should be considered in the differential diagnosis of one or more adjacent small spiculated masses, especially if the masses are nonpalpable and have long spicules.

Mucinous Carcinoma
Mucinous carcinoma accounts for about 2% of breast cancers (1). Mucin is a dominant feature at histologic examination (Fig 4). From your last experience with an upper respiratory infection, you will recall that mucin is a semisolid substance. If palpable, these cancers tend to manifest as soft masses. Because of the predominance of mucin, this carcinoma typically manifests as a low-density, relatively well-defined or microlobulated oval or lobular mass at mammography (Fig 4) (25). It belongs to the list of "circumscribed" cancers (Fig 5); on spot compression views (obtained with or without magnification), the margins of circumscribed cancers are usually ill defined rather than sharply defined (Fig 4). On US scans, mucinous carcinomas are often heterogeneous in echogenicity and may have mixed solid and cystic components (25). Posterior acoustic enhancement is common; posterior acoustic shadowing is very uncommon (25). On MR images, mucinous carcinomas are one of the few cancers that have very high signal intensity on T2-weighted images (26), again likely due to the watery nature of mucin (Fig 6).

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 4a: Mammograms in 59-year-old woman. (a) Right craniocaudal view shows an oval circumscribed mass (arrow). (b) Right craniocaudal spot compression view shows a low-density mass with ill-defined margins (arrows). Core-needle biopsy revealed mucinous carcinoma. (c) Histologic section shows well-defined margin (curved arrow) with nests of tumor cells (straight arrows) floating in a pool of mucin. (Hematoxyllin-eosin stain; original magnification, x100.)

View larger version (101K): [in this window] [in a new window] [Download PPT slide]   Figure 4b: Mammograms in 59-year-old woman. (a) Right craniocaudal view shows an oval circumscribed mass (arrow). (b) Right craniocaudal spot compression view shows a low-density mass with ill-defined margins (arrows). Core-needle biopsy revealed mucinous carcinoma. (c) Histologic section shows well-defined margin (curved arrow) with nests of tumor cells (straight arrows) floating in a pool of mucin. (Hematoxyllin-eosin stain; original magnification, x100.)

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 4c: Mammograms in 59-year-old woman. (a) Right craniocaudal view shows an oval circumscribed mass (arrow). (b) Right craniocaudal spot compression view shows a low-density mass with ill-defined margins (arrows). Core-needle biopsy revealed mucinous carcinoma. (c) Histologic section shows well-defined margin (curved arrow) with nests of tumor cells (straight arrows) floating in a pool of mucin. (Hematoxyllin-eosin stain; original magnification, x100.)

View larger version (14K): [in this window] [in a new window] [Download PPT slide]   Figure 5: List of circumscribed cancers of the breast. * = Margins are often ill defined on spot compression views.

View larger version (71K): [in this window] [in a new window] [Download PPT slide]   Figure 6a: Images in 53-year-old woman with new focal asymmetry in the right breast. (a) T2-weighted fat-suppressed MR image (repetition time msec/echo time msec, 4320/123) of both breasts shows 1.8-cm lobular very high-signal-intensity mass (arrow) with relatively circumscribed margins in the right breast at the 6-o'clock position. (b) T1-weighted fat-suppressed contrast material–enhanced MR image (30/5) of both breasts shows a mass with mild rim enhancement (arrow). Core-needle biopsy revealed IDC with predominantly mucinous features. Since less than 90% of the tumor had mucinous features, this lesion was not considered a "pure" mucinous carcinoma.

View larger version (70K): [in this window] [in a new window] [Download PPT slide]   Figure 6b: Images in 53-year-old woman with new focal asymmetry in the right breast. (a) T2-weighted fat-suppressed MR image (repetition time msec/echo time msec, 4320/123) of both breasts shows 1.8-cm lobular very high-signal-intensity mass (arrow) with relatively circumscribed margins in the right breast at the 6-o'clock position. (b) T1-weighted fat-suppressed contrast material–enhanced MR image (30/5) of both breasts shows a mass with mild rim enhancement (arrow). Core-needle biopsy revealed IDC with predominantly mucinous features. Since less than 90% of the tumor had mucinous features, this lesion was not considered a "pure" mucinous carcinoma.

Medullary carcinoma typically manifests as a round mass with ill-defined or circumscribed margins at mammography (Fig 7) (27,30). On US scans, the mass is either homogeneously hypoechoic or hypoechoic with mild heterogeneity (30).

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 7: Right MLO mammographic view in 48-year-old woman with a palpable mass (triangular marker) demonstrates a round equal-density (isodense) mass with ill-defined margins (arrow). Core biopsy revealed medullary carcinoma. Linear metallic opacities are wires on the skin that mark scars from prior reduction mammoplasty.

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 8a: (a) Right craniocaudal (left) and MLO (right) mammographic views in 72-year-old woman with palpable mass in the right breast at 10-o'clock position (triangular marker). An oval, circumscribed, high-density mass (arrows) corresponds to the palpable finding. (b) Power Doppler US scan shows the mass is oval with circumscribed margins and contains an intracystic solid mass (straight arrow). Cyst walls are focally thickened in some areas (curved arrow). Blood flow is seen in the intracystic mass, confirming that it does not represent debris or clot. US-guided core needle biopsy was performed, revealing invasive papillary carcinoma. A clip was placed at the time of core biopsy to aid in localization prior to surgical excision.

View larger version (73K): [in this window] [in a new window] [Download PPT slide]   Figure 8b: (a) Right craniocaudal (left) and MLO (right) mammographic views in 72-year-old woman with palpable mass in the right breast at 10-o'clock position (triangular marker). An oval, circumscribed, high-density mass (arrows) corresponds to the palpable finding. (b) Power Doppler US scan shows the mass is oval with circumscribed margins and contains an intracystic solid mass (straight arrow). Cyst walls are focally thickened in some areas (curved arrow). Blood flow is seen in the intracystic mass, confirming that it does not represent debris or clot. US-guided core needle biopsy was performed, revealing invasive papillary carcinoma. A clip was placed at the time of core biopsy to aid in localization prior to surgical excision.

The clinical and imaging findings of papillary carcinoma can be recalled by remembering that benign intraductal papillomas likewise frequently manifest with nipple discharge, are most common in the central breast, and are the most common benign intraductal mass.

	MALIGNANT NEOPLASMS OF STROMAL ORIGIN

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

 
Breast tumors may originate from the supporting tissue of the breast, including fibromuscular tissue, blood vessels, and lymph system. These tumors have varied appearances but clinical history and imaging features often raise suspicion of these rare tumors.

Phyllodes Tumor
Phyllodes tumor accounts for fewer than 1% of breast cancers (33) and typically manifests as a rapidly enlarging palpable mass in middle-aged to older women (33). In general, women who present with a large palpable breast mass and who state that the mass was not present several months ago usually have some degree of psychologic denial of their disease. However, phyllodes tumor exhibits such extremely rapid growth that the large palpable mass actually may develop over a sequence of months.

The mammographic appearance is often telling—a very large, relatively circumscribed, round or oval mass in a middle-aged or older woman (Fig 9). The mass may become extremely large (34). At close inspection, the margins are often ill defined rather than sharply circumscribed. When detected at a screening examination, the appearance may mimic a fibroadenoma (Fig 10) (35). The US appearance is also similar to that of fibroadenoma, though phyllodes tumor more frequently contains cystic spaces than does a benign fibroadenoma (33). The margins of a benign fibroadenoma are sharply defined on US scans, whereas the margins of a phyllodes tumor are typically ill defined.

View larger version (42K): [in this window] [in a new window] [Download PPT slide]   Figure 9: Mammographic views in 76-year-old woman with a palpable mass in the left breast that has developed over the previous 6 months. Bilateral craniocaudal (left) and mediolateral (right) views show an 18-cm, oval, circumscribed, high-density mass occupying most of the breast. Biopsy revealed low-grade phyllodes tumor. In a young woman, a very large mass such as this would be more likely to represent a giant fibroadenoma.

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 10a: Images in 47-year-old woman. (a) Left MLO view from screening mammogram shows an oval, circumscribed, equal-density mass (arrowhead). (b) US scan shows mass is oval and hypoechoic with a horizontal orientation. While the mass resembles fibroadenoma at US, the margins are ill defined (straight arrows) and the mass contains several cleftlike cystic spaces (curved arrow). US-guided core-needle biopsy revealed phyllodes tumor.

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 10b: Images in 47-year-old woman. (a) Left MLO view from screening mammogram shows an oval, circumscribed, equal-density mass (arrowhead). (b) US scan shows mass is oval and hypoechoic with a horizontal orientation. While the mass resembles fibroadenoma at US, the margins are ill defined (straight arrows) and the mass contains several cleftlike cystic spaces (curved arrow). US-guided core-needle biopsy revealed phyllodes tumor.

Phyllodes tumors may be classified as (a) benign, low grade, or high grade or as (b) low grade or high grade, with the latter classification currently gaining favor since all must be surgically excised (36). A phyllodes tumor can be difficult to distinguish from a proliferative fibroadenoma at core-needle biopsy, and excision may be necessary to make the diagnosis (37–39). Wide excision is indicated even for low-grade tumors, since a phyllodes tumor can be locally aggressive (40). The risk of metastatic disease is very uncommon with low-grade phyllodes tumors. The older name for these tumors was cystosarcoma phylloides, which hints at the behavior. Like sarcomas, these lesions metastasize hematogenously, most commonly to the lungs (41). A chest x-ray therefore provides initial staging. Sentinel node biopsy and axillary dissection are not indicated, since these tumors do not spread through the lymphatic system (41). Radiation therapy and chemotherapy are not useful (41).

High-grade phyllodes tumors may contain sarcomatous elements such as chondrosarcoma, osteosarcoma, and leiomyosarcoma (42). The margins of these lesions may become less defined. Metastatic lesions may likewise exhibit sarcomatous elements, even when the primary lesion did not (42). Prognosis is poor for lesions containing sarcomatous elements as they tend to follow the behavior of sarcomas.

Angiosarcoma
Angiosarcoma as a primary breast tumor is rare, accounting for fewer than 1% of breast tumors. Angiosarcoma is more likely to occur in an area treated with radiation, whether occurring in the breast, lung, kidney, or other soft-tissue organ. It typically manifests as an ill-defined highly vascular mass (43). Angiosarcoma may occasionally be difficult to differentiate from pseudoangiomatous stroma hyperplasia, an uncommon lesion in the breast (44), though an immunohistochemical stain for endothelial cells will be negative in pseudoangiomatous stroma hyperplasia. The incidence of angiosarcoma increases beginning 5 years after radiation therapy for treatment of breast cancer (Fig 11) (45). The mass is typically not located in the lumpectomy bed, which would be more concerning for recurrent breast cancer. Metastasis occurs hematogenously, most commonly to the lungs. Prognosis is poor.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 11a: Mammograms of left breast in 54-year-old woman who underwent left lumpectomy and radiation therapy for IDC 10 years earlier. Patient had new onset of redness and swelling in the breast and was referred for imaging because of concern of recurrent inflammatory breast carcinoma. (a) Craniocaudal view obtained 2 years earlier shows a small scar at 7-o'clock position (arrow) (linear metallic opacity marks the scar on the skin). (b) Craniocaudal view now shows a new 1.8-cm mass at 5-o'clock position (curved arrow), distant from the lumpectomy site (straight arrow). Trabecular thickening is present due to diffuse breast edema. Biopsy of the new mass revealed angiosarcoma.

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 11b: Mammograms of left breast in 54-year-old woman who underwent left lumpectomy and radiation therapy for IDC 10 years earlier. Patient had new onset of redness and swelling in the breast and was referred for imaging because of concern of recurrent inflammatory breast carcinoma. (a) Craniocaudal view obtained 2 years earlier shows a small scar at 7-o'clock position (arrow) (linear metallic opacity marks the scar on the skin). (b) Craniocaudal view now shows a new 1.8-cm mass at 5-o'clock position (curved arrow), distant from the lumpectomy site (straight arrow). Trabecular thickening is present due to diffuse breast edema. Biopsy of the new mass revealed angiosarcoma.

View larger version (77K): [in this window] [in a new window] [Download PPT slide]   Figure 12: Mammogram in 45-year-old woman with palpable mass in the left breast developing over several months. Craniocaudal view shows a large densely calcified mass in subareolar region. Excisional biopsy revealed primary osteosarcoma of the breast. (Reprinted, with permission, from reference 46.)

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 13: MLO view of left breast from screening mammogram in 66-year-old woman shows an 8-mm, oval, circumscribed, low-density mass (arrow) in the inferior portion of the breast. Core-needle biopsy revealed adenoid cystic carcinoma. Wide surgical excision was performed without axillary dissection.

	METASTATIC LESIONS

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma is most frequently of concern when bilateral axillary adenopathy is seen on the mammogram. The differential diagnosis of bilateral axillary adenopathy is long, however, and includes reactive lymph node hyperplasia, histoplasmosis, human immunodeficiency virus, and metastatic disease. In our practice, women with bilateral axillary adenopathy seen mammographically but with an otherwise normal mammogram are referred for medical evaluation of the numerous potential causes. These women may be occasionally referred back to us for US-guided biopsy of a lymph node to exclude lymphoma, if no other cause is apparent. Core biopsy rather than fine-needle aspiration biopsy is performed, as lymph node architecture is needed to make a definitive diagnosis of lymphoma. Primary lymphoma of the breast is rare and beyond the scope of this review.

Metastatic Melanoma
Metastatic melanoma may manifest as multiple round or oval circumscribed masses similar to metastatic carcinomas. However, metastatic melanoma should also be considered when there is unilateral adenopathy or enlargement of an intramammary lymph node. Primary breast carcinoma that may be mammographically occult should be suspected first and foremost in the setting of unilateral axillary adenopathy. However, melanoma metastatic to the axillary or intramammary lymph nodes may be seen occasionally, particularly when the primary lesion was on the back or upper abdomen.

Metastatic Carcinoma
Metastatic carcinomas in the breast typically manifest as multiple round or oval circumscribed masses (Fig 14) (50). The margins may appear circumscribed, though often ill defined on spot compression views (obtained with or without magnification) or US scans. At clinical examination, discrete masses are typically palpable, although the breasts may become firmer without discrete palpable lumps. Fine-needle aspiration biopsy is often adequate to confirm the diagnosis of metastatic disease if the patient has a known primary carcinoma.

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 14: Bilateral MLO mammographic views of the breasts in 67-year-old woman with history of lung cancer thought to be in remission. She palpated a lump in left breast and also noted her breasts were becoming firmer. Views show numerous circumscribed masses with a dominant mass in left breast at the 2-o'clock position corresponding to the palpable abnormality (arrow). Fine-needle aspiration biopsy revealed metastatic lung carcinoma.

View larger version (55K): [in this window] [in a new window] [Download PPT slide]   Figure 15a: Images in 53-year-old woman with history of treatment for leukemia and a large firm mass in the right breast. (a) Bilateral mammogram shows global asymmetry, with right breast diffusely denser than the left (curved arrows). Ill-defined focal asymmetries are present in both breasts (white arrows). Note enlarged right axillary lymph node (black arrow). (b) US scan shows multiple ill-defined hypoechoic areas with hyperechoic margins (arrows). Core biopsy revealed leukemic infiltrates.

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 15b: Images in 53-year-old woman with history of treatment for leukemia and a large firm mass in the right breast. (a) Bilateral mammogram shows global asymmetry, with right breast diffusely denser than the left (curved arrows). Ill-defined focal asymmetries are present in both breasts (white arrows). Note enlarged right axillary lymph node (black arrow). (b) US scan shows multiple ill-defined hypoechoic areas with hyperechoic margins (arrows). Core biopsy revealed leukemic infiltrates.

	SUMMARY

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

ILC spreads in sheets of tumor cells of a single layer, similar to a spiderweb. The infiltrative growth of ILC results in palpable thickening at clinical examination, architectural distortion at mammography, and vague shadowing at US. With advanced ILC, the breast may appear to have decreased in size at mammography (the shrinking breast). ILC tends to metastasize to peritoneal surfaces, resulting in ascites, hydronephrosis, and pelvic masses.

The well-differentiated subtypes of IDC have a better prognosis than does IDC not otherwise specified. They are characterized by slow growth (except medullary carcinoma) and a relatively circumscribed appearance at mammography (except for tubular carcinoma, which appears spiculated at mammography but is "tubular" or "cool"). Mucinous carcinoma has low density on a mammogram and high signal intensity on T2-weighted MR images due to high mucin content. Medullary carcinoma mimics poorly differentiated carcinoma at histologic examination but also has a good prognosis.

A very large, relatively circumscribed breast mass is usually a phyllodes tumor if the patient is middle aged or older or a giant fibroadenoma if the patient is young. Smaller phyllodes tumors mimic fibroadenomas but occur in middle-aged and older women.

Angiosarcomas and osteosarcomas occur more frequently after radiation therapy and should be considered with the appearance of a highly vascular mass and large unusual-appearing calcification, respectively.

Metastatic lesions to the breast may manifest as adenopathy, such as non-Hodgkin lymphoma, or multiple relatively circumscribed masses. Infiltrative metastasis, such as rhabdomyosarcoma and leukemia, may mimic ILC.

	ESSENTIALS

TOP ABSTRACT INTRODUCTION INVASIVE LOBULAR CARCINOMA SUBTYPES OF DUCTAL CARCINOMA MALIGNANT NEOPLASMS OF STROMAL... METASTATIC LESIONS SUMMARY ESSENTIALS References

 

• Invasive lobular carcinoma infiltrates the breast in thin sheets of cells similar to a spiderweb, typically resulting in thickening at clinical examination, architectural distortion without a central mass at mammography, and areas of shadowing on a US scan.
  
• The well-differentiated subtypes of invasive ductal carcinoma (IDC) (mucinous, medullary, tubular, and papillary carcinomas) have a better prognosis than IDC not otherwise specified, because the former are characterized by slow growth (except medullary carcinoma) and a relatively circumscribed appearance at mammography (except tubular carcinoma, which appears spiculated at mammography but is "tubular" or "cool").
  
• Phyllodes tumor mimics fibroadenoma in appearance but is typically large in size and occurs in middle-aged and older women.
  

	ACKNOWLEDGMENTS

 
I thank Kristin Atkins, MD, assistant professor of pathology, University of Virginia, for providing the histologic images.

	FOOTNOTES

 

Abbreviations: DCIS = ductal carcinoma in situ • IDC = invasive ductal carcinoma • ILC = invasive lobular carcinoma • MLO = mediolateral oblique

Author stated no financial relationship to disclose.

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