(Radiographics. 1999;19:S11-S26.)
© RSNA, 1999
Unusual Breast Lesions: Radiologic-Pathologic Correlation1
Jay M. Feder, MD,
Ellen Shaw de Paredes, MD,
Jacquelyn P. Hogge, MD and
Jennifer J. Wilken, MD
1 From the Departments of Radiology (J.M.F., E.S.D., J.P.H.) and Pathology (J.J.W.), Medical College of Virginia, Virginia Commonwealth University, 1200 E Marshall St, Richmond, VA 23298. Recipient of a Certificate of Merit award for a scientific exhibit at the 1998 RSNA scientific assembly. Received March 29, 1999; revision requested April 20 and received May 17; accepted May 17. Address reprint requests to E.S.D.
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Abstract
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Unusual lesions of the breast can present a diagnostic challenge. These lesions include systemic diseases, benign tumors, and primary and metastatic malignancies. Lymphadenopathy is the most common mammographic finding associated with collagen vascular disease. Wegener granulomatosis may manifest as an irregular, high-density mass simulating breast cancer. Diabetic fibrous mastopathy manifests at mammography as very dense breast tissue and at ultrasonography (US) as an irregular, hypoechoic mass with striking posterior acoustic shadowing simulating malignancy. Fibromatosis simulates malignancy at mammography as an irregularly shaped, uncalcified, high-density mass and at US as an irregular, hypoechoic mass with posterior acoustic shadowing. At US, granular cell tumor may manifest as a solid, poorly marginated mass with marked posterior acoustic shadowing or may appear more benign. At mammography, hamartomas are typically well-circumscribed, round to oval masses with a thin, radiopaque pseudocapsule; at US, they manifest as a sharply defined, heterogeneous oval mass or as normal glandular tissue. Phyllodes tumor manifests at mammography as a large, well-circumscribed oval or lobulated mass; at US, it usually manifests as an inhomogeneous, solid-appearing mass. At mammography, primary breast lymphoma manifests as a relatively circumscribed mass or a solitary, indistinctly marginated, uncalcified mass. Metastatic lesions may manifest mammographically as single or multiple masses or as diffuse skin thickening; at US, they tend to have circumscribed margins with low-level internal echoes. Radiologists should be familiar with the characteristic mammographic appearances of these lesions and should consider benign and systemic causes in the differential diagnosis when malignant-appearing findings are encountered.
Index Terms: Breast, diseases, 00.60, 00.622 • Breast neoplasms, 00.31, 00.3112, 00.314, 00.3192, 00.32, 00.329, 00.34 • Breast neoplasms, diagnosis, 00.11, 00.1298 • Breast neoplasms, metastases, 00.33 • Hamartoma, 00.314 • Lymphoma, 00.34 • Wegener granulomatosis, 00.622
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INTRODUCTION
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It is important for radiologists to be familiar with the mammographic appearance of a variety of unusual breast lesions. These lesions include systemic diseases (eg, collagen vascular disease, vasculitis, hyperparathyroidism, steatocystoma multiplex), rare benign tumors (eg, fibromatosis [extraabdominal desmoid tumor], granular cell tumor, hamartoma [fibroadenolipoma], phyllodes tumor [cystosarcoma phyllodes]), uncommon primary malignant tumors (eg, lymphoma, sarcoma and carcinosarcoma, adenoid cystic carcinoma), and metastatic lesions (Table). In this article, we discuss and illustrate the mammographic appearance of a variety of rare breast lesions and provide radiologic-pathologic correlation when available.
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SYSTEMIC DISEASES
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Systemic diseases infrequently involve the breast, but mammographic findings may be striking. Many disorders have a characteristic appearance at mammography that is diagnostic for the disease, whereas others may mimic cancer.
Collagen Vascular Disease
A number of mammographic findings have been associated with collagen vascular disease. The most common finding is lymphadenopathy, which is usually bilateral. Lymphadenopathy is associated with several of the collagen vascular disorders, including rheumatoid arthritis (Fig 1) (1,2), systemic lupus erythematosus, scleroderma, and psoriatic arthritis. Other causes of lymphadenopathy that should be considered include granulomatous diseases (eg, tuberculosis sarcoidosis) (Fig 2) (3), acquired immunodeficiency syndrome, mononucleosis, leukemia, and lymphoma. Faint metallic deposits may be identified in axillary lymph nodes in rheumatoid arthritis patients who have undergone long-term treatment with gold salt injections and may mimic the calcifications seen in metastatic axillary lymph nodes (4) (Fig 3).
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Figure 2a. Sarcoidosis in a 38-year-old woman who presented to the emergency department with abdominal pain. Abdominal ultrasonography (US) and computed tomography showed diffuse intraabdominal lymphadenopathy. (a) Right mediolateral oblique mammogram reveals enlarged axillary lymph nodes (arrow). (b) Axillary US image shows a lymph node (arrow) as a hypoechoic, circumscribed mass with a hyperechoic center that represents the fatty hilum of the node. Findings at bilateral axillary US confirmed lymphadenopathy. (c) Photomicrograph (original magnification, x400; Diff-Quik stain) of aspirate obtained at US-guided fine-needle biopsy demonstrates collections of epithelioid histiocytes with abundant cytoplasm and footprint-shaped nuclei (arrow) that together form noncaseating granulomas. This finding is consistent with sarcoidosis. Follow-up chest radiography demonstrated stage III sarcoidosis changes.
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Figure 2b. Sarcoidosis in a 38-year-old woman who presented to the emergency department with abdominal pain. Abdominal ultrasonography (US) and computed tomography showed diffuse intraabdominal lymphadenopathy. (a) Right mediolateral oblique mammogram reveals enlarged axillary lymph nodes (arrow). (b) Axillary US image shows a lymph node (arrow) as a hypoechoic, circumscribed mass with a hyperechoic center that represents the fatty hilum of the node. Findings at bilateral axillary US confirmed lymphadenopathy. (c) Photomicrograph (original magnification, x400; Diff-Quik stain) of aspirate obtained at US-guided fine-needle biopsy demonstrates collections of epithelioid histiocytes with abundant cytoplasm and footprint-shaped nuclei (arrow) that together form noncaseating granulomas. This finding is consistent with sarcoidosis. Follow-up chest radiography demonstrated stage III sarcoidosis changes.
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Figure 2c. Sarcoidosis in a 38-year-old woman who presented to the emergency department with abdominal pain. Abdominal ultrasonography (US) and computed tomography showed diffuse intraabdominal lymphadenopathy. (a) Right mediolateral oblique mammogram reveals enlarged axillary lymph nodes (arrow). (b) Axillary US image shows a lymph node (arrow) as a hypoechoic, circumscribed mass with a hyperechoic center that represents the fatty hilum of the node. Findings at bilateral axillary US confirmed lymphadenopathy. (c) Photomicrograph (original magnification, x400; Diff-Quik stain) of aspirate obtained at US-guided fine-needle biopsy demonstrates collections of epithelioid histiocytes with abundant cytoplasm and footprint-shaped nuclei (arrow) that together form noncaseating granulomas. This finding is consistent with sarcoidosis. Follow-up chest radiography demonstrated stage III sarcoidosis changes.
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Figure 3. Rheumatoid arthritis in a postmenopausal woman who received gold salt injections. Right mediolateral oblique screening mammogram shows metallic deposits in the axillary lymph nodes (arrows).
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Dermatomyositis is an autoimmune collagen vascular disease of unknown cause that is characterized by chronic inflammation and degeneration of striated muscle and skin. It most frequently affects middle-aged women in the 5th and 6th decades of life. The diagnosis is made on the basis of clinical symptoms (weakness of the proximal muscle groups, especially of the extremities), elevated levels of serum muscle enzyme (creatine phosphokinase and aldolase), and findings at muscle biopsy. At mammography, dermatomyositis may manifest as extensive bizarre, dystrophic subcutaneous calcifications (5) (Fig 4). Breast cancer has been reported to be associated with dermatomyositis (6), although ovarian cancer is much more commonly associated with this disease. Patients with dermatomyositis are usually treated with a long-term course of corticosteroids, but methotrexate, azathioprine, and intravenously administered immune globulin have been used in patients who are resistant to or intolerant of corticosteroids. Patients with an associated neoplasm generally have a poor prognosis.
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Figure 4. Dermatomyositis in a 38-year-old woman with a history of scleroderma and dermatomyositis. Left mediolateral oblique mammogram demonstrates bizarre, confluent dystrophic subcutaneous calcifications that obscure most of the breast parenchyma (arrow). No palpable mass was found at clinical examination. BB indicates the location of a mole on the skin.
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Vasculitis
Wegener granulomatosis is a rare, systemic autoimmune disorder that is characterized pathologically by a necrotizing granulomatous vasculitis. It primarily involves the lungs, upper respiratory tract, and kidneys. Wegener granulomatosis usually begins in middle age and has a slight male predilection. The diagnosis is made with biopsy of involved tissues, and high serologic titers for the presence of antineutrophil cytoplasmic antibody are specific. Affected patients usually respond to treatment with cyclophosphamide. Corticosteroids are usually of limited efficacy. Wegener granulomatosis may rarely be seen at mammography as an irregularly shaped, high-density mass simulating breast cancer (7,8) (Fig 5).
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Figure 5. Wegener granulomatosis in a postmenopausal woman with a palpable breast mass. Mammogram shows an irregularly shaped, high-density mass (arrow) simulating breast cancer. Wegener granulomatosis was confirmed at subsequent excisional biopsy.
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Diabetic fibrous mastopathy was first described in 1984 by Soler and Khardori (9). It is a benign lesion found in patients with type 1 diabetes mellitus and manifests about 20 years after the onset of diabetes. Fibrous mastopathy usually manifests as a very firm or hard, nontender breast mass in young women (10,11). At mammography, very dense breast tissue is seen, occasionally with an irregular focal mass or an area of asymmetry (12) (Fig 6a). At US, an irregular hypoechoic mass with striking posterior acoustic shadowing may be seen simulating a malignancy (Fig 6b). At pathologic analysis, there are increased numbers of fibroblasts in a primarily collagenous stroma (Fig 6c). Predominantly B-cell lymphocytes are found in and around the walls of small blood vessels, indicating that the pathologic process is a form of vasculitis.
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Figure 6a. Diabetic fibrous mastopathy in a 35-year-old woman with long-standing type 1 diabetes mellitus who presented with a palpable mass in the right breast. (a) Bilateral craniocaudal mammogram shows mirror-image focal areas of dense parenchyma in both breasts (arrowheads). BB indicates the palpable mass in the right breast; the lesion in the left breast was nonpalpable. (b) US image of the palpable mass demonstrates an irregular, hypoechoic mass with very dense posterior acoustic shadowing (arrows). (c) Photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows dense stromal fibrosis obliterating breast lobules and ducts (arrows).
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Figure 6b. Diabetic fibrous mastopathy in a 35-year-old woman with long-standing type 1 diabetes mellitus who presented with a palpable mass in the right breast. (a) Bilateral craniocaudal mammogram shows mirror-image focal areas of dense parenchyma in both breasts (arrowheads). BB indicates the palpable mass in the right breast; the lesion in the left breast was nonpalpable. (b) US image of the palpable mass demonstrates an irregular, hypoechoic mass with very dense posterior acoustic shadowing (arrows). (c) Photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows dense stromal fibrosis obliterating breast lobules and ducts (arrows).
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Figure 6c. Diabetic fibrous mastopathy in a 35-year-old woman with long-standing type 1 diabetes mellitus who presented with a palpable mass in the right breast. (a) Bilateral craniocaudal mammogram shows mirror-image focal areas of dense parenchyma in both breasts (arrowheads). BB indicates the palpable mass in the right breast; the lesion in the left breast was nonpalpable. (b) US image of the palpable mass demonstrates an irregular, hypoechoic mass with very dense posterior acoustic shadowing (arrows). (c) Photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows dense stromal fibrosis obliterating breast lobules and ducts (arrows).
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Hyperparathyroidism
Patients with hyperparathyroidism, especially those with secondary hyperparathyroidism due to chronic renal failure, may develop extensive diffuse vascular calcifications in the breast (13). Diffuse coarse, subcutaneous breast calcifications can also be seen, particularly in patients undergoing dialysis (14) (Fig 7).
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Figure 7a. Secondary hyperparathyroidism due to chronic renal failure in a 57-year-old woman with end-stage renal disease secondary to hypertension. The patient was undergoing hemodialysis after having undergone peritoneal dialysis for the past 6 years. (a) Craniocaudal mammogram of the left breast demonstrates early vascular calcification. (b) Craniocaudal mammogram of the left breast obtained 1 year later demonstrates dramatic progressive development of diffuse coarse soft-tissue (large arrows) and vascular (small arrows) calcifications. These findings are characteristic of secondary hyperparathyroidism.
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Figure 7b. Secondary hyperparathyroidism due to chronic renal failure in a 57-year-old woman with end-stage renal disease secondary to hypertension. The patient was undergoing hemodialysis after having undergone peritoneal dialysis for the past 6 years. (a) Craniocaudal mammogram of the left breast demonstrates early vascular calcification. (b) Craniocaudal mammogram of the left breast obtained 1 year later demonstrates dramatic progressive development of diffuse coarse soft-tissue (large arrows) and vascular (small arrows) calcifications. These findings are characteristic of secondary hyperparathyroidism.
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Steatocystoma Multiplex
Steatocystoma multiplex is an uncommon benign cutaneous disorder with autosomal dominant inheritance. The disease manifests as numerous palpable intradermal oil cysts ranging from 2 mm to 2 cm in diameter. These cysts occur primarily on the trunk, proximal extremities, and external genitalia. The condition occurs more frequently in adolescent boys or young men and is progressive (although usually asymptomatic) in nature. Steatocystoma multiplex manifests radiographically as extensive oil cysts in the subcutaneous area (15) (Fig 8).
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Figure 8a. Steatocystoma multiplex in a 63-year-old woman with palpable subcutaneous nodules in the cleavage area of the breasts and in the arms. (a) Mammogram of the cleavage area shows multiple oil cysts with peripheral calcifications in the subcutaneous areas of both breasts (arrows). (b) Mammogram (magnification view) demonstrates an oil cyst (arrow) in the subcutaneous area of the right breast. (c) Radiograph of the forearm obtained with soft-tissue technique shows a similar oil cyst (arrow).
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Figure 8b. Steatocystoma multiplex in a 63-year-old woman with palpable subcutaneous nodules in the cleavage area of the breasts and in the arms. (a) Mammogram of the cleavage area shows multiple oil cysts with peripheral calcifications in the subcutaneous areas of both breasts (arrows). (b) Mammogram (magnification view) demonstrates an oil cyst (arrow) in the subcutaneous area of the right breast. (c) Radiograph of the forearm obtained with soft-tissue technique shows a similar oil cyst (arrow).
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Figure 8c. Steatocystoma multiplex in a 63-year-old woman with palpable subcutaneous nodules in the cleavage area of the breasts and in the arms. (a) Mammogram of the cleavage area shows multiple oil cysts with peripheral calcifications in the subcutaneous areas of both breasts (arrows). (b) Mammogram (magnification view) demonstrates an oil cyst (arrow) in the subcutaneous area of the right breast. (c) Radiograph of the forearm obtained with soft-tissue technique shows a similar oil cyst (arrow).
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UNCOMMON BENIGN TUMORS
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Fibromatosis (Extraabdominal Desmoid Tumor)
Fibromatosis is a benign, localized, infiltrating mass composed of fibroblasts and collagen that is typically found in the abdominal wall and on rare occasions in the breast. The lesion usually manifests as a single palpable, very firm, non-tender mass that is sometimes fixed to the pectoral fascia. Skin retraction may also be present, a finding that suggests breast cancer (16). Although the lesion tends to recur locally if it is not widely excised, it does not metastasize (17). At mammography, the lesion appears as an irregularly shaped, high-density spiculated or indistinct mass without associated calcifications and is indistinguishable from breast cancer (18–20) (Fig 9a). At US, fibromatosis manifests as an irregular, hypoechoic mass with posterior acoustic shadowing and simulates malignancy. Pathologic analysis demonstrates mature fibroblasts arranged in interlacing bundles without nuclear atypia or increased mitotic activity (Fig 9b).
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Figure 9a. Fibromatosis in a 26-year-old woman who presented with a palpable mass in the right breast with concomitant nipple retraction. (a) Right mediolateral oblique mammogram demonstrates a spiculated high-density mass overlying the pectoral muscle in the posterior aspect of the breast simulating cancer (arrow). BB indicates mole. Subsequent excisional biopsy with wide margins revealed an extraabdominal desmoid tumor (fibromatosis). (b) Photomicrograph (original magnification, x100; H-E stain) shows fascicles of bland fibroblasts (arrows) entrapping benign breast lobules (arrowheads) and fat.
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Figure 9b. Fibromatosis in a 26-year-old woman who presented with a palpable mass in the right breast with concomitant nipple retraction. (a) Right mediolateral oblique mammogram demonstrates a spiculated high-density mass overlying the pectoral muscle in the posterior aspect of the breast simulating cancer (arrow). BB indicates mole. Subsequent excisional biopsy with wide margins revealed an extraabdominal desmoid tumor (fibromatosis). (b) Photomicrograph (original magnification, x100; H-E stain) shows fascicles of bland fibroblasts (arrows) entrapping benign breast lobules (arrowheads) and fat.
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Granular Cell Tumor
Granular cell tumor was first described as a separate clinicopathologic entity in 1926 by Abrikossoff (21) and was originally given the name granular cell myoblastoma. Although the lesion was originally thought to arise from muscle, it is now thought to derive from Schwann cells (22). Approximately 8% of granular cell tumors occur within the breast. The lesion usually manifests as a painless, firm, usually mobile mass in the upper aspect of the breast. Occasionally, the mass is fixed to the pectoral fascia, chest wall, or skin with resulting dimpling, retraction, or edema and simulates breast cancer (23). Granular cell tumor is usually benign and is cured with wide local excision. Recurrent granular cell tumor has been documented in patients who have undergone inadequate excision (24). Rare instances of malignant granular cell tumors with metastases have been documented (25,26). A variety of mammographic manifestations have been described, ranging from a round, circumscribed mass with well-defined borders to an indistinct mass (Fig 10a) to a spiculated mass that is indistinguishable from cancer (Fig 10b). Microcalcifications are usually not present (27). At US, granular cell tumor may manifest as a solid, poorly marginated mass with marked posterior acoustic shadowing (28); alternatively, it may have a more benign appearance (ie, more circumscribed with posterior acoustic enhancement) (Fig 11). At pathologic analysis, granular cell tumor manifests as a pattern of closely packed nests of cells with abundant cytoplasm containing numerous fine eosinophilic granules. A tendency to form syncytial cords and sheets that infiltrate the surrounding tissue is often noted; this finding imitates the infiltrative pattern of breast cancer (29) (Fig 12).
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Figure 10a. Granular cell tumor in a 47-year-old asymptomatic woman who presented for routine screening mammography. (a) Right mediolateral oblique mammogram shows a high-density mass with indistinct margins in the posterior aspect of the breast (arrow). Subsequent excisional biopsy with preoperative needle localization revealed the mass to be a granular cell tumor. (b) Specimen radiograph obtained following excisional biopsy shows an irregularly shaped, high-density spiculated mass with indistinct margins closely resembling cancer.
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Figure 10b. Granular cell tumor in a 47-year-old asymptomatic woman who presented for routine screening mammography. (a) Right mediolateral oblique mammogram shows a high-density mass with indistinct margins in the posterior aspect of the breast (arrow). Subsequent excisional biopsy with preoperative needle localization revealed the mass to be a granular cell tumor. (b) Specimen radiograph obtained following excisional biopsy shows an irregularly shaped, high-density spiculated mass with indistinct margins closely resembling cancer.
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Figures 11, 12. (11) Granular cell tumor in a 46-year-old woman who presented with a palpable mass that had first been noticed 6 weeks earlier. US image demonstrates a lobulated, hypoechoic solid mass (arrow). Subsequent excisional biopsy revealed a granular cell tumor. (12) Granular cell tumor. Photomicrograph (original magnification, x200; H-E stain) demonstrates nests of polyhedral cells with abundant eosinophilic granular cytoplasm and bland, centrally located nuclei.
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Figures 11, 12. (11) Granular cell tumor in a 46-year-old woman who presented with a palpable mass that had first been noticed 6 weeks earlier. US image demonstrates a lobulated, hypoechoic solid mass (arrow). Subsequent excisional biopsy revealed a granular cell tumor. (12) Granular cell tumor. Photomicrograph (original magnification, x200; H-E stain) demonstrates nests of polyhedral cells with abundant eosinophilic granular cytoplasm and bland, centrally located nuclei.
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Hamartoma (Fibroadenolipoma)
Hamartoma of the breast was first described in 1971 by Arrigoni et al (30) as a benign proliferation of fibrous, glandular, and fatty tissue surrounded by a thin capsule of connective tissue (30). The majority of these lesions occur in women over 35 years of age. At clinical examination, hamartomas are usually occult, but they may manifest as a large, mobile, soft to firm mass. At mammography, they are typically well-circumscribed, round to oval masses containing both fat and soft-tissue density with a thin, radiopaque pseudocapsule that becomes visible around a portion of the mass when fat is present on both sides (Fig 13). Occasionally, hamartomas may manifest mammographically as a predominantly soft-tissue density, a finding that complicates the diagnosis. Hamartomas displace or overlap normal tissue around their margins. Coarse dystrophic or punctate calcifications are rarely seen (31,32). When the lesion is asymptomatic and demonstrates a typical mammographic appearance, the patient can be followed up mammographically without the need for US or intervention. At US, a sharply defined, heterogeneous oval mass is seen, or the lesion may manifest as normal glandular tissue (33). At pathologic analysis, varying amounts of fatty, fibrous, and glandular tissue are identified. A true fibrous capsule is not present, and it is the compressed adjacent tissues that produce the pseudocapsule seen at mammography (Fig 14).
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Figures 13, 14. Hamartoma. (13) On a left craniocaudal mammogram, hamartoma has a classic benign appearance as a well-circumscribed, fat-containing mass with mixed density and a thin, radiopaque pseudocapsule (arrows). (14) Photomicrograph (original magnification, x100; H-E stain) shows a well-encapsulated lesion composed of varying amounts of normal benign breast elements. Increased numbers of benign lobules with fibrocystic changes, cystically dilated glands, and apocrine metaplasia are also seen (arrowheads).
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Figures 13, 14. Hamartoma. (13) On a left craniocaudal mammogram, hamartoma has a classic benign appearance as a well-circumscribed, fat-containing mass with mixed density and a thin, radiopaque pseudocapsule (arrows). (14) Photomicrograph (original magnification, x100; H-E stain) shows a well-encapsulated lesion composed of varying amounts of normal benign breast elements. Increased numbers of benign lobules with fibrocystic changes, cystically dilated glands, and apocrine metaplasia are also seen (arrowheads).
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Phyllodes Tumor (Cystosarcoma Phyllodes)
Phyllodes tumor was first described in 1838 by Johannes Muller (34) and was termed cystosarcoma phyllodes because of its leaflike pattern of growth. Phyllodes tumor most commonly manifests as a rapidly growing mass in women 30–50 years of age and can be quite large at initial presentation (35). At mammography, phyllodes tumor manifests as a large, well-circumscribed oval or lobulated mass that may have a radiolucent halo (36) (Fig 15). Coarse, plaquelike calcifications are rarely seen. At US, an inhomogeneous, solid-appearing mass is the most common manifestation. However, a solid mass containing cystic spaces and demonstrating posterior acoustic enhancement strongly suggests the diagnosis of phyllodes tumor (Fig 16). At histologic analysis, the tumor resembles a giant fibroadenoma with both epithelial and stromal components. The stroma is fibrous but is more cellular than that of a fibroadenoma. Phyllodes tumor can be confused with a hypercellular fibroadenoma at core biopsy; consequently, this procedure is not recommended if phyllodes tumor is thought to be the most likely diagnosis and excisional biopsy should be performed. Benign phyllodes tumors typically have smooth, noninfiltrative borders, and the stromal cells show minimal nuclear atypia and low mitotic activity (Fig 17). Up to 25% of phyllodes tumors contain areas of malignant degeneration and have infiltrative borders (Fig 18). Both benign and malignant phyllodes tumors have a tendency to recur if not widely excised (37) (Fig 19). Approximately 10% of all phyllodes tumors act as true sarcomas with metastases via hematogenous spread.
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Figures 15, 16. (15) Phyllodes tumor in a 46-year-old woman with a newly developed, rapidly enlarging mass. Right mediolateral mammogram shows a large, oval, well-defined isodense mass (large arrow) with a radiolucent halo (small arrows). A high-grade phyllodes tumor with extension to the pectoral muscle was seen at excisional biopsy. At pathologic analysis, the margins of the surgical specimen were positive for tumor. (16) Phyllodes tumor. US image shows an inhomogeneous solid mass with cystic spaces and posterior acoustic enhancement (arrows).
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Figures 15, 16. (15) Phyllodes tumor in a 46-year-old woman with a newly developed, rapidly enlarging mass. Right mediolateral mammogram shows a large, oval, well-defined isodense mass (large arrow) with a radiolucent halo (small arrows). A high-grade phyllodes tumor with extension to the pectoral muscle was seen at excisional biopsy. At pathologic analysis, the margins of the surgical specimen were positive for tumor. (16) Phyllodes tumor. US image shows an inhomogeneous solid mass with cystic spaces and posterior acoustic enhancement (arrows).
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Figure 17. Benign phyllodes tumor. Photomicrograph (original magnification, x100; H-E stain) shows a well-encapsulated tumor composed of leaflike processes lined by bland epithelium (arrows). The somewhat hypercellular stroma demonstrates no atypia and low mitotic activity.
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Figure 18a. Malignant phyllodes tumor. (a) Photomicrograph (original magnification, x100; H-E stain) demonstrates more cellular stroma with condensation of the stroma around the glands (arrows) compared with the benign phyllodes tumor (cf Fig 17). The amorphous pink areas in the clefts represent proteinaceous material that has taken up the eosinophilic stain. (b) Higher-power photomicrograph (original magnification, x400; H-E stain) demonstrates significant nuclear atypia and increased mitoses (arrows) compared with the benign phyllodes tumor.
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Figure 18b. Malignant phyllodes tumor. (a) Photomicrograph (original magnification, x100; H-E stain) demonstrates more cellular stroma with condensation of the stroma around the glands (arrows) compared with the benign phyllodes tumor (cf Fig 17). The amorphous pink areas in the clefts represent proteinaceous material that has taken up the eosinophilic stain. (b) Higher-power photomicrograph (original magnification, x400; H-E stain) demonstrates significant nuclear atypia and increased mitoses (arrows) compared with the benign phyllodes tumor.
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UNCOMMON MALIGNANT TUMORS
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Lymphoma
Lymphoma rarely occurs as a primary tumor of the breast and represents only 0.1%–0.5% of all breast malignancies (38,39). B- cell lymphoma occurs more frequently than T-cell lymphoma. Primary breast lymphoma may manifest clinically as a palpable mass with or without skin changes (eg, retraction, erythema, peau d'orange) that simulate inflammatory breast cancer. At mammography, primary lymphoma of the breast manifests as a relatively circumscribed mass or a solitary, indistinctly marginated, uncalcified mass; in cases of dense breast parenchyma, it may not be visualized as a discrete mass at all (40) (Fig 20). Chemotherapy and radiation therapy are used to treat primary lymphoma. Their use is dependent on the stage and histologic subtype of the disease. Radical surgery is not indicated.
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Figure 20a. Primary lymphoma in a 40-year-old woman who presented for routine screening mammography. (a) Left mediolateral oblique mammogram shows a partially well-circumscribed, oval, palpable, high-density mass (arrow). Several small tumor nodules are seen posteriorly (arrowheads). Excisional biopsy revealed a primary large cell non-Hodgkin lymphoma. The patient underwent radiation therapy and chemotherapy and experienced interval resolution of the small posterior nodules. (b) Photomicrograph (original magnification, x400; H-E stain) demonstrates large cell non-Hodgkin lymphoma of the breast. The lesion is characterized by sheets of cells with large, convoluted nuclei containing prominent nucleoli and scant cytoplasm. (c) Follow-up mammogram obtained 3 years later shows a new bilobed mass posteriorly (arrow). BB indicates mole. A new, small cleaved cell-type non-Hodgkin lymphoma was identified at excisional biopsy. (d) Photomicrograph (original magnification, x400; H-E stain) shows nodular aggregates of small cleaved lymphocytes. Results of immunologic studies were consistent with small cleaved cell-type non-Hodgkin lymphoma.
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Figure 20b. Primary lymphoma in a 40-year-old woman who presented for routine screening mammography. (a) Left mediolateral oblique mammogram shows a partially well-circumscribed, oval, palpable, high-density mass (arrow). Several small tumor nodules are seen posteriorly (arrowheads). Excisional biopsy revealed a primary large cell non-Hodgkin lymphoma. The patient underwent radiation therapy and chemotherapy and experienced interval resolution of the small posterior nodules. (b) Photomicrograph (original magnification, x400; H-E stain) demonstrates large cell non-Hodgkin lymphoma of the breast. The lesion is characterized by sheets of cells with large, convoluted nuclei containing prominent nucleoli and scant cytoplasm. (c) Follow-up mammogram obtained 3 years later shows a new bilobed mass posteriorly (arrow). BB indicates mole. A new, small cleaved cell-type non-Hodgkin lymphoma was identified at excisional biopsy. (d) Photomicrograph (original magnification, x400; H-E stain) shows nodular aggregates of small cleaved lymphocytes. Results of immunologic studies were consistent with small cleaved cell-type non-Hodgkin lymphoma.
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Figure 20c. Primary lymphoma in a 40-year-old woman who presented for routine screening mammography. (a) Left mediolateral oblique mammogram shows a partially well-circumscribed, oval, palpable, high-density mass (arrow). Several small tumor nodules are seen posteriorly (arrowheads). Excisional biopsy revealed a primary large cell non-Hodgkin lymphoma. The patient underwent radiation therapy and chemotherapy and experienced interval resolution of the small posterior nodules. (b) Photomicrograph (original magnification, x400; H-E stain) demonstrates large cell non-Hodgkin lymphoma of the breast. The lesion is characterized by sheets of cells with large, convoluted nuclei containing prominent nucleoli and scant cytoplasm. (c) Follow-up mammogram obtained 3 years later shows a new bilobed mass posteriorly (arrow). BB indicates mole. A new, small cleaved cell-type non-Hodgkin lymphoma was identified at excisional biopsy. (d) Photomicrograph (original magnification, x400; H-E stain) shows nodular aggregates of small cleaved lymphocytes. Results of immunologic studies were consistent with small cleaved cell-type non-Hodgkin lymphoma.
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Figure 20d. Primary lymphoma in a 40-year-old woman who presented for routine screening mammography. (a) Left mediolateral oblique mammogram shows a partially well-circumscribed, oval, palpable, high-density mass (arrow). Several small tumor nodules are seen posteriorly (arrowheads). Excisional biopsy revealed a primary large cell non-Hodgkin lymphoma. The patient underwent radiation therapy and chemotherapy and experienced interval resolution of the small posterior nodules. (b) Photomicrograph (original magnification, x400; H-E stain) demonstrates large cell non-Hodgkin lymphoma of the breast. The lesion is characterized by sheets of cells with large, convoluted nuclei containing prominent nucleoli and scant cytoplasm. (c) Follow-up mammogram obtained 3 years later shows a new bilobed mass posteriorly (arrow). BB indicates mole. A new, small cleaved cell-type non-Hodgkin lymphoma was identified at excisional biopsy. (d) Photomicrograph (original magnification, x400; H-E stain) shows nodular aggregates of small cleaved lymphocytes. Results of immunologic studies were consistent with small cleaved cell-type non-Hodgkin lymphoma.
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Sarcoma and Carcinosarcoma
Sarcomas are malignancies of mesenchymal tissues that rarely occur as primary breast malignancies and represent about 0.7% of all breast cancers. After angiosarcoma, the most common histologic types of breast sarcomas are malignant fibrous histiocytoma, liposarcoma, and fibrosarcoma. Sarcomas are often highly malignant tumors that enlarge rapidly and metastasize hematogenously (41,42). They most commonly manifest as a painless, mobile mass. The only mammographic finding that is diagnostic for breast sarcoma is osteoid matrix, which indicates osteogenic sarcoma (43) (Fig 21).
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Figures 21, 22. (21) Carcino-osteosarcoma in a postmenopausal woman who presented with a palpable mass in the right breast. Spot magnification mammogram shows amorphous mineralization of osteoid matrix (arrow). Excisional biopsy revealed a carcino-osteosarcoma. (22) Carcinosarcoma in a 65-year-old asymptomatic woman. (a) Left mediolateral oblique screening mammogram reveals an ill-defined mass with calcifications (arrow). Pathologic analysis of a specimen obtained with stereotactic core needle biopsy demonstrated a carcinosarcoma. (b) Photomicrograph (original magnification, x100; H-E stain) shows the tumor to be characterized by malignant epithelial elements (ductal carcinoma in situ with comedonecrosis [arrows], intermixed with malignant stroma—in this case, osteosarcoma [arrowheads] and undifferentiated sarcoma [bottom]).
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Carcinosarcomas are the rarest primary malignancies of the breast (<0.1% of cases). These lesions are malignant tumors containing both carcinomatous and sarcomatous elements that are derived separately from epithelial and mesenchymal tissues (44,45) (Fig 22).
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Figures 21, 22. (21) Carcino-osteosarcoma in a postmenopausal woman who presented with a palpable mass in the right breast. Spot magnification mammogram shows amorphous mineralization of osteoid matrix (arrow). Excisional biopsy revealed a carcino-osteosarcoma. (22) Carcinosarcoma in a 65-year-old asymptomatic woman. (a) Left mediolateral oblique screening mammogram reveals an ill-defined mass with calcifications (arrow). Pathologic analysis of a specimen obtained with stereotactic core needle biopsy demonstrated a carcinosarcoma. (b) Photomicrograph (original magnification, x100; H-E stain) shows the tumor to be characterized by malignant epithelial elements (ductal carcinoma in situ with comedonecrosis [arrows], intermixed with malignant stroma—in this case, osteosarcoma [arrowheads] and undifferentiated sarcoma [bottom]).
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Figures 21, 22. (21) Carcino-osteosarcoma in a postmenopausal woman who presented with a palpable mass in the right breast. Spot magnification mammogram shows amorphous mineralization of osteoid matrix (arrow). Excisional biopsy revealed a carcino-osteosarcoma. (22) Carcinosarcoma in a 65-year-old asymptomatic woman. (a) Left mediolateral oblique screening mammogram reveals an ill-defined mass with calcifications (arrow). Pathologic analysis of a specimen obtained with stereotactic core needle biopsy demonstrated a carcinosarcoma. (b) Photomicrograph (original magnification, x100; H-E stain) shows the tumor to be characterized by malignant epithelial elements (ductal carcinoma in situ with comedonecrosis [arrows], intermixed with malignant stroma—in this case, osteosarcoma [arrowheads] and undifferentiated sarcoma [bottom]).
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Adenoid Cystic Carcinoma
Adenoid cystic carcinoma of the breast was first described in 1946 by Foote and Stewart (46). The tumor demonstrates a strikingly characteristic microscopic pattern similar to that of adenoid cystic carcinoma of the salivary glands and accounts for 0.1%–0.4% of all breast cancers. Adenoid cystic carcinoma of the breast displays slowly progressive growth and rarely metastasizes to the axillary lymph nodes and therefore has a favorable prognosis (47,48). At mammography, the lesion may be relatively well defined (49) (Fig 23a); at pathologic analysis, it is characterized by the presence of mucin within pseudocysts found in the tumor (Fig 23b).
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Figure 23a. Adenoid cystic carcinoma. (a) Left craniocaudal mammogram demonstrates a lobulated, isodense mass with relatively well-defined margins in the lateral portion of the breast (arrow) corresponding to a palpable, mobile nodule that was found at clinical examination. Adenoid cystic carcinoma was diagnosed at excisional biopsy. (b) Photomicrograph (original magnification, x100; H-E stain) shows tubular and cribriform collections of basaloid cells infiltrating the breast tissue. The cystic spaces in the cribriform areas contain either hyaline basement membrane-like material (straight arrow) or pale, basophilic mucoid material (curved arrow).
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Figure 23b. Adenoid cystic carcinoma. (a) Left craniocaudal mammogram demonstrates a lobulated, isodense mass with relatively well-defined margins in the lateral portion of the breast (arrow) corresponding to a palpable, mobile nodule that was found at clinical examination. Adenoid cystic carcinoma was diagnosed at excisional biopsy. (b) Photomicrograph (original magnification, x100; H-E stain) shows tubular and cribriform collections of basaloid cells infiltrating the breast tissue. The cystic spaces in the cribriform areas contain either hyaline basement membrane-like material (straight arrow) or pale, basophilic mucoid material (curved arrow).
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Metastases to the Breast
Breast metastases from nonmammary primary tumors are uncommon, representing 0.5%–2.0% of all breast malignancies. At palpation, metastases feel similar in size to their appearance at mammography; in contrast, primary breast cancers tend to feel larger than their mammographic appearance. In addition, metastases do not tend to cause retraction of the skin or nipple. At mammography, metastatic lesions may manifest as single or multiple masses or as diffuse skin thickening (edema pattern) (Fig 24). Metastases usually appear as round masses with circumscribed or ill-defined borders. Irregular shape, spiculations, and microcalcifications may be seen but are rare (Figs 25, 26). Metastatic lesions are much more likely to be multiple or bilateral than primary cancers. Metastases are often found in the subcutaneous fat, whereas primary breast cancers develop in the glandular tissue. At US, metastatic masses tend to have circumscribed margins with low-level internal echoes and, occasionally, posterior acoustic enhancement. The most common extramammary cancers that metastasize to the breast are melanoma, non-Hodgkin lymphoma, sarcoma, and carcinoma of the lung, stomach, ovaries, and renal cells (Figs 25, 26). In men, prostate cancer that metastasizes to the breast is the most common manifestation (50–52).
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Figures 24-26. (24) Metastatic fallopian tube carcinoma in a 45-year-old woman who presented with peau d'orange skin changes in the left breast. Left mediolateral oblique mammogram shows diffuse skin thickening (arrowheads). Incisional biopsy revealed metastatic fallopian tube carcinoma. (25) Metastatic lymphoma in an 85-year-old woman with known lymphoma who presented for routine screening mammography. Left mediolateral oblique mammogram shows an irregularly shaped, isodense mass (arrow). Metastatic lymphoma was found at excisional biopsy. (26) Metastatic papillary carcinoma from an unknown primary site in a 65-year-old woman. Right mediolateral oblique mammogram demonstrates a large, high-density mass in the axilla. Peripheral psammomatous calcifications are also present (arrows). Biopsy revealed nonmammary papillary cancer with no identifiable primary site.
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Figures 24-26. (24) Metastatic fallopian tube carcinoma in a 45-year-old woman who presented with peau d'orange skin changes in the left breast. Left mediolateral oblique mammogram shows diffuse skin thickening (arrowheads). Incisional biopsy revealed metastatic fallopian tube carcinoma. (25) Metastatic lymphoma in an 85-year-old woman with known lymphoma who presented for routine screening mammography. Left mediolateral oblique mammogram shows an irregularly shaped, isodense mass (arrow). Metastatic lymphoma was found at excisional biopsy. (26) Metastatic papillary carcinoma from an unknown primary site in a 65-year-old woman. Right mediolateral oblique mammogram demonstrates a large, high-density mass in the axilla. Peripheral psammomatous calcifications are also present (arrows). Biopsy revealed nonmammary papillary cancer with no identifiable primary site.
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Figures 24-26. (24) Metastatic fallopian tube carcinoma in a 45-year-old woman who presented with peau d'orange skin changes in the left breast. Left mediolateral oblique mammogram shows diffuse skin thickening (arrowheads). Incisional biopsy revealed metastatic fallopian tube carcinoma. (25) Metastatic lymphoma in an 85-year-old woman with known lymphoma who presented for routine screening mammography. Left mediolateral oblique mammogram shows an irregularly shaped, isodense mass (arrow). Metastatic lymphoma was found at excisional biopsy. (26) Metastatic papillary carcinoma from an unknown primary site in a 65-year-old woman. Right mediolateral oblique mammogram demonstrates a large, high-density mass in the axilla. Peripheral psammomatous calcifications are also present (arrows). Biopsy revealed nonmammary papillary cancer with no identifiable primary site.
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CONCLUSIONS
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A wide spectrum of unusual benign and malignant lesions may be encountered at mammography. Therefore, it is important that radiologists be familiar with lesions that have a characteristic mammographic appearance and do not require further imaging. Radiologists should also consider benign and systemic causes in the differential diagnosis when malignant-appearing findings are encountered.
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Footnotes
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Abbreviation: H-E = hematoxylin-eosin
CME FEATURE This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician's Recognition Award. To obtain credit, see the questionnaire on pp S259-S266.
LEARNING OBJECTIVES After reading this article and taking the test, the reader will:
• Be able to develop a differential diagnosis for unusual benign conditions that may mimic cancer at mammography.
• Recognize the major distinguishing characteristics of unusual benign tumors that may be seen at mammography.
• Be able to develop a differential diagnosis for conditions that may produce bilateral axillary lymphadenopathy seen at mammography.
• Recognize the imaging features of metastatic breast cancers as opposed to primary and nonprimary cancers that arise within the breast.
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References
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Bruwer A, Nelson GW, Spark RP. Punctate intranodal gold deposits simulating microcalcifications on mammograms. Radiology 1987; 163:87-88.[Abstract/Free Full Text]
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Gyves-Ray KM, Adler DD. Dermatomyositis: an unusual cause of breast calcifications. Breast Dis 1989; 2:195-201.
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Bonnetblanc JM, Bernard P, Fayol J. Dermatomyositis and malignancy: a multicenter cooperative study. Dermatologica 1990; 180:212-216.[Medline]
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Deininger HK. Wegener's granulomatosis of the breast. Radiology 1985; 154:59-60.[Abstract/Free Full Text]
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Abstract
INTRODUCTION
