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Radiologic Evaluation of Breast Disorders Related to Pregnancy and Lactation¹

¹ From the Unit of Breast Imaging, Department of Diagnostic Radiology (J.M.S., M.C., S.T., R.G.), and the Department of Pathology (E.L.), Hospital de la Santa Creu i Sant Pau, Avda Sant Antoni Maria Claret 167, 08025 Barcelona, Spain; and the Departments of Breast Imaging (J.M.S., A.G.) and Breast Pathology (P.L.), CEDIMMA, Barcelona, Spain. Recipient of a Certificate of Merit award for an education exhibit at the 2006 RSNA Annual Meeting. Received February 21, 2007; revision requested April 5 and received May 22; accepted May 30. All authors have no financial relationships to disclose. Address correspondence to J.M.S. (e-mail: Jsabate{at}santpau.es).

	Abstract

Top Abstract LEARNING OBJECTIVES Introduction Physiologic Changes during... Radiologic Evaluation of the... Medicolegal Issues Benign Disorders Closely Related... Inflammatory and Infectious... Benign Tumors Malignant Tumors Conclusions References

 
During pregnancy and lactation, the breast can be affected by a variety of specific and unique disorders, including benign disorders closely related to physiologic changes, inflammatory and infectious diseases, juvenile papillomatosis, and benign and malignant tumors. Patients with pregnancy-associated breast carcinoma tend to have more advanced neoplasms at diagnosis and a poorer prognosis due to delayed diagnosis and a more aggressive biologic pattern. Pregnancy-related Burkitt lymphoma characteristically manifests with bilateral and diffuse involvement of the breasts. Fibroadenoma may manifest with growth, infarction, large cysts, prominent ducts, and secretory hyperplasia during pregnancy and lactation. Galactocele is the breast lesion most commonly found during lactation and manifests as either pseudolipoma, a cystic mass with a fat-fluid level, or pseudohamartoma. Tumors and diseases affecting the breasts during pregnancy and lactation are basically the same as those observed in nonpregnant women but may have a different appearance. The sensitivity of mammography in pregnant and lactating women is decreased due to increased parenchymal density. Instead, ultrasonography is the most appropriate radiologic method for evaluating breast masses in this setting and is particularly useful in the diagnosis and treatment of abscesses. Knowledge of the unique entities that are specifically related to pregnancy and lactation and of their radiologic-pathologic appearances can help the radiologist make the correct diagnosis.

© RSNA, 2007

	LEARNING OBJECTIVES

Top Abstract LEARNING OBJECTIVES Introduction Physiologic Changes during... Radiologic Evaluation of the... Medicolegal Issues Benign Disorders Closely Related... Inflammatory and Infectious... Benign Tumors Malignant Tumors Conclusions References

 
After reading this article and taking the test, the reader will be able to:

• Recognize breast disorders related to pregnancy and lactation and the radiologic-pathologic changes that can occur in these disorders in this setting.
  
• Describe the most common radiologic manifestations of each disorder and the value of different diagnostic procedures.
  
• Discuss the most common and relevant clinical and radiologic manifestations of pregnancy-associated breast carcinoma.
  

	Introduction

Top Abstract LEARNING OBJECTIVES Introduction Physiologic Changes during... Radiologic Evaluation of the... Medicolegal Issues Benign Disorders Closely Related... Inflammatory and Infectious... Benign Tumors Malignant Tumors Conclusions References

 
Pregnancy and lactation represent unique physiologic states that induce notable changes in the mammary glands in response to hormonal stimulation. Tumors or disorders affecting the breasts in pregnant or lactating women are usually the same as those observed in nonpregnant women. However, some breast disorders are unique to pregnancy and lactation. Most breast tumors diagnosed during pregnancy and lactation existed beforehand but manifest during this time due to changes or growth that take place in some of them in this setting. Unfortunately, the assessment of breast disorders related to pregnancy and lactation has received scant attention in the radiology literature.

Although most disorders related to pregnancy and lactation are benign, so-called pregnancy-associated breast carcinoma (PABC) represents up to 3% of all breast malignancies. PABC constitutes a particularly dramatic situation that deserves special consideration because it involves both the mother and the fetus. The diagnosis of breast cancer during pregnancy and lactation is difficult both clinically and radiologically due to the striking hormone-induced changes that occur in breast tissue. This is the critical point in the management of breast cancer during pregnancy and lactation. A delay in diagnosis secondary to these intrinsic difficulties or to a lack of awareness of the possibility of breast cancer in this setting has been postulated as the major factor responsible for the advanced stage and poor prognosis that, unfortunately, are associated with PABC. Therefore, it is crucial that both gynecologists and radiologists be aware of this possible diagnosis. All masses found during pregnancy and lactation should be evaluated carefully, since diagnosis of nonrelevant or physiologic lumps secondary to hormonal stimulation can be established only after meticulous radiologic assessment (1).

In this article, we discuss and illustrate the pathologic changes that cause most radiologic and cytopathologic diagnostic difficulties during pregnancy and lactation. In addition, we assess medicolegal issues related to pregnancy, particularly the use of mammography during pregnancy and the risk it poses to the fetus. We emphasize the value of ultrasonography (US) as the most appropriate and effective method of evaluating breast disorders during pregnancy and lactation. The Table lists these disorders according to their respective causes.

	Physiologic Changes during Pregnancy and Lactation

Top Abstract LEARNING OBJECTIVES Introduction Physiologic Changes during... Radiologic Evaluation of the... Medicolegal Issues Benign Disorders Closely Related... Inflammatory and Infectious... Benign Tumors Malignant Tumors Conclusions References

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  (a, b) Pathologic changes during pregnancy (gestational hyperplasia). (a) Photomicrograph (original magnification, x20; hematoxylin-eosin [H-E] stain) obtained during the 1st trimester of pregnancy shows slight acinar proliferation with minimal secretory change. Involution of the fibrofatty stroma is also noted. (b) Photomicrograph (original magnification, x40; H-E stain) obtained during the 3rd trimester of pregnancy reveals intense lobular proliferation. The cells appear enlarged with increased cytoplasm and enlarged nuclei. Note also the dramatic stromal involution and increased vascularity (arrows). (c) Pathologic changes during lactation (secretory hyperplasia). Photomicrograph (original magnification, x40; H-E stain) shows notable growth and distention of lobules, with cells appearing markedly enlarged with vacuolated cytoplasm. Nuclei are more enlarged, and milk is retained in the ducts (*).

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  (a, b) Pathologic changes during pregnancy (gestational hyperplasia). (a) Photomicrograph (original magnification, x20; hematoxylin-eosin [H-E] stain) obtained during the 1st trimester of pregnancy shows slight acinar proliferation with minimal secretory change. Involution of the fibrofatty stroma is also noted. (b) Photomicrograph (original magnification, x40; H-E stain) obtained during the 3rd trimester of pregnancy reveals intense lobular proliferation. The cells appear enlarged with increased cytoplasm and enlarged nuclei. Note also the dramatic stromal involution and increased vascularity (arrows). (c) Pathologic changes during lactation (secretory hyperplasia). Photomicrograph (original magnification, x40; H-E stain) shows notable growth and distention of lobules, with cells appearing markedly enlarged with vacuolated cytoplasm. Nuclei are more enlarged, and milk is retained in the ducts (*).

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  (a, b) Pathologic changes during pregnancy (gestational hyperplasia). (a) Photomicrograph (original magnification, x20; hematoxylin-eosin [H-E] stain) obtained during the 1st trimester of pregnancy shows slight acinar proliferation with minimal secretory change. Involution of the fibrofatty stroma is also noted. (b) Photomicrograph (original magnification, x40; H-E stain) obtained during the 3rd trimester of pregnancy reveals intense lobular proliferation. The cells appear enlarged with increased cytoplasm and enlarged nuclei. Note also the dramatic stromal involution and increased vascularity (arrows). (c) Pathologic changes during lactation (secretory hyperplasia). Photomicrograph (original magnification, x40; H-E stain) shows notable growth and distention of lobules, with cells appearing markedly enlarged with vacuolated cytoplasm. Nuclei are more enlarged, and milk is retained in the ducts (*).

These changes are more notable during lactation, the secretory state, when the cytoplasm of lobular cells becomes vacuolated and secretion progressively accumulates in distended lobular glands. Nuclei are hyperchromatic and often have small nucleoli. Myoepithelial cells are flattened and attenuated. This process is the result of high levels of prolactin secondary to the rapid withdrawal of progesterone that occurs suddenly after delivery. Prolactin, in conjunction with metabolic hormones such as insulin, corticosteroids, and thyroid and growth hormones, induces the formation and secretion of fat, lactose, and proteins (lactogenesis II), which constitute the basic nutrients of milk. Thus, lactating breasts show marked distention of lobular glands and accumulation of secretion in ducts (Fig 1c). Lactogenesis I and II are hormonally driven. Milk ejection is caused by oxytocin and modulated by complex neuroendocrine interactions. In contrast with lactogenesis I and II, the maintenance of milk production during lactation (lactogenesis III) is due to the autocrine system, a neuroendocrine mechanism that is fundamentally based on the release of oxytocin in the posterior pituitary gland stimulated by breast-feeding (2–6). US has been considered helpful in the assessment of the milk ejection process because it can be used to measure ductal diameter, and this assessment would be a useful clinical test in infants with consistently low milk intake (7).

Involution of the breast occurs over a period of about 3 months after lactation ceases. The post-lactating breast is characterized by marked lobular atrophy (3).

	Radiologic Evaluation of the Breast during Pregnancy and Lactation: State of the Art

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The previously described physiologic changes lead to a diffuse and marked increase in parenchymal density. At mammography, the gland appears very dense, heterogeneously coarse, nodular, and confluent, with a marked decrease in adipose tissue and a prominent ductal pattern (Fig 2). These features, together with the high density usually found in young women, severely decrease the sensitivity of mammography, which normally ranges from 70% to 90%. Many tumors exhibit only secondary and subtle findings such as architectural distortion or asymmetric density; therefore, mammographic diagnosis of breast cancer may be difficult without the support of US (8–13). However, high-density parenchyma is not seen in all patients. Furthermore, some pregnant or lactating patients have unchanged breast density compared with baseline mammographic findings (14). In lactating women, mammography should be performed immediately after breast-feeding, when breast density has decreased.

View larger version (71K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Mammographic changes during lactation. (a) Baseline mammogram obtained before pregnancy shows minimal scattered fibroglandular densities with glandular components lower than 50%, type 2 American College of Radiology (ACR) classification. (b) Mammogram obtained during lactation shows a marked diffuse increase in density.

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Mammographic changes during lactation. (a) Baseline mammogram obtained before pregnancy shows minimal scattered fibroglandular densities with glandular components lower than 50%, type 2 American College of Radiology (ACR) classification. (b) Mammogram obtained during lactation shows a marked diffuse increase in density.

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 3.  US changes during pregnancy. Breast US image obtained during gestation shows diffuse enlargement of the nonfatty glandular component and global hypoechogenicity.

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  US changes during lactation. (a) US image reveals diffuse enlargement of the glandular component with diffuse hyperechogenicity. The latter finding is related to the production of milk, which is rich in fat. (b) US image shows a prominent ductal system, a characteristic feature of lactation due to milk secretion. (c) Color Doppler US image (shown in black and white) reveals increased vascularity (arrow). This finding can also be seen during pregnancy but is more marked during lactation.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  US changes during lactation. (a) US image reveals diffuse enlargement of the glandular component with diffuse hyperechogenicity. The latter finding is related to the production of milk, which is rich in fat. (b) US image shows a prominent ductal system, a characteristic feature of lactation due to milk secretion. (c) Color Doppler US image (shown in black and white) reveals increased vascularity (arrow). This finding can also be seen during pregnancy but is more marked during lactation.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 4c.  US changes during lactation. (a) US image reveals diffuse enlargement of the glandular component with diffuse hyperechogenicity. The latter finding is related to the production of milk, which is rich in fat. (b) US image shows a prominent ductal system, a characteristic feature of lactation due to milk secretion. (c) Color Doppler US image (shown in black and white) reveals increased vascularity (arrow). This finding can also be seen during pregnancy but is more marked during lactation.

In summary, US should be considered as the initial imaging test in symptomatic pregnant or lactating women. In our opinion, although the use of mammography is controversial, this modality is helpful in the assessment of tumors and should be performed if malignancy is suspected because it is particularly effective in the detection of microcalcifications or subtle distorting areas, features that are not commonly depicted with US (1,8–10,13,14,17).

	Medicolegal Issues

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Mammography
The impact of prenatal exposure to ionizing radiation depends on three factors: radiation dose, anatomic distribution of radiation, and stage of fetal development at the time of exposure. It is well known that during the first 2 months of pregnancy (organogenesis), the fetus is the most susceptible to radiation-induced malformations, which include congenital lesions, growth retardation, perinatal death, and the potential to develop postnatal neoplasias. These malformations are believed to occur with exposure to more than 0.05 Gy of radiation (18). Standard two-view mammography of each breast performed with abdominal shielding subjects the fetus to only 0.004 Gy of radiation. Thus, contrary to popular belief, mammography with abdominal shielding can be performed if necessary during pregnancy—basically for the staging of breast cancer—with minimal or no risk to the fetus. Nevertheless, current recommendations are to avoid mammography during the 1st trimester, instead evaluating breast diseases with US (1,18–20).

Cytologic Analysis
As mentioned earlier, several cellular changes normally occur in the epithelium of the breasts of pregnant or lactating women. Most of these changes are so marked that they can lead to a false-positive diagnosis of carcinoma. Therefore, the cytologic diagnosis of breast lesions during pregnancy and lactation should be made with caution. An experienced cytopathologist with specific knowledge of the pregnancy is required to avoid false-positive diagnosis. In this setting, core biopsy represents an effective alternative and is mandatory if malignancy is suspected (21,22).

Core Biopsy
Core biopsy is the standard procedure for assessing breast masses during pregnancy and lactation. It is a safe, cost-effective, and easy method for making a precise diagnosis, thereby avoiding surgical biopsy. However, caution should be exercised in this setting. The risk of bleeding is slightly increased during any intervention performed on the breast of a pregnant or lactating woman due to the increased vascularity associated with pregnancy and lactation. The risk of infection is also increased due to ductal dilatation, milk production, and breast-feeding traumas, as is the risk of milk fistula formation. Obviously, these complications are more prone to develop with core biopsy than with fine-needle aspiration, but they occur infrequently. These risks must be minimized by having the patient discontinue breast-feeding prior to undergoing biopsy, paying close attention to hemostasis, and performing the procedure with strict asepsia (23).

MR Imaging
Current opinion states that MR imaging should be avoided during pregnancy. The ACR recommends the use of MR imaging only in those situations in which the risk-benefit ratio is clear, and specifically states that contrast agents should not be routinely used in pregnant patients (24). In the setting of PABC, in which large tumors are commonly seen at diagnosis, the current indications for complementary MR imaging in breast cancer staging do not seem appropriate; US and mammography are sufficient. To date, however, there is no conclusive evidence that MR imaging produces toxic effects on embryos; many studies have failed to demonstrate teratogenesis or carcinogenesis caused by either electromagnetic fields or endovenous contrast agents (25,26). The European Society of Radiology recently stated that use of gadolinium-based contrast material during pregnancy is probably safe. In fact, the quantity of gadolinium expected to cross the placenta is low, and contrast material is rapidly eliminated by the kidneys (27). Contrast material–enhanced MR imaging can be used during lactation, although given that a small amount of gadolinium is excreted into breast milk, it is prudent not to breast-feed for 24 hours after the examination, having previously actively expressed milk from each breast (26,27).

	Benign Disorders Closely Related to Physiologic Changes

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Gestational and Secretory Hyperplasia
Microcalcifications secondary to gestational hyperplasia (related to pregnancy) or secretory hyperplasia (related to lactation) may be depicted mammographically. Two different mammographic manifestations have been reported. Microcalcifications are most commonly round, with a diffuse or focal distribution. Less commonly, they have an irregular appearance, a linear distribution, and a branching pattern closely resembling malignancy. The two manifestations can coexist: Round punctate calcifications represent hyperplasia in the lobular acini, whereas linear calcifications correspond to ductal hyperplasia (Fig 5) (28–30).

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Microcalcifications secondary to secretory hyperplasia during lactation in a 35-year-old woman. (a) Image from a mammographic study performed for nonrelevant breast pain shows regional foci of suspect microcalcifications (circled), a finding that led to prompt core biopsy. Note the presence of both linear and punctate microcalcifications, the former related to ductal hyperplasia and the latter to lobular growth. (b) Photomicrograph (original magnification, x10; H-E stain) demonstrates the characteristic features of secretory hyperplasia.

View larger version (168K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Microcalcifications secondary to secretory hyperplasia during lactation in a 35-year-old woman. (a) Image from a mammographic study performed for nonrelevant breast pain shows regional foci of suspect microcalcifications (circled), a finding that led to prompt core biopsy. Note the presence of both linear and punctate microcalcifications, the former related to ductal hyperplasia and the latter to lobular growth. (b) Photomicrograph (original magnification, x10; H-E stain) demonstrates the characteristic features of secretory hyperplasia.

Spontaneous Bloody Nipple Discharge
Spontaneous bloody nipple discharge is an uncommon clinical condition during pregnancy and lactation. It usually appears in the 3rd trimester of pregnancy, when the vascularity of the breast is significantly increased and changes in the epithelium are more marked, resulting in bleeding, probably related to minimal, often unnoticed, trauma. Not surprisingly, therefore, occult blood has been demonstrated in up to 20% of women with nonhematic nipple discharge during pregnancy and in 15% of lactating women (32,33). This phenomenon usually ceases with the onset of nursing but in severe cases can continue for awhile during lactation. In lactating women, false bloody secretion due to an injured nipple caused by baby suction must first be excluded.

Cytologic analysis of nipple secretion must be performed with caution, and normal physiologic changes must not be mistaken for neoplasia. Clinical follow-up is advised if no pathologic results are found and physical and US examinations are normal. Nevertheless, if pathologic nipple secretion is suspected, US and galactography should be performed to exclude organic endoductal proliferations such as papillomas or intraductal carcinomas. Galactography is recommended if bloody secretion is limited to one duct because spontaneous secretion usually involves more than one duct. It must be remembered that nipple discharge represents an uncommon manifestation of PABC (Figs 6, 7) (32–34).

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Intraductal carcinoma in a 31-year-old woman who presented with bloody nipple discharge in the 3rd trimester of pregnancy. (a) Mammogram obtained with abdominal shielding reveals extensive suspect foci of linear and pleomorphic microcalcifications (arrows) with a segmental distribution (circled). Galactography was performed because the bloody discharge was limited to one duct. (b) Galactogram shows multiple small, irregular intraductal filling defects (arrows) secondary to neoplastic proliferation involving the same pathologic lobe that was seen at mammography.

View larger version (98K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Intraductal carcinoma in a 31-year-old woman who presented with bloody nipple discharge in the 3rd trimester of pregnancy. (a) Mammogram obtained with abdominal shielding reveals extensive suspect foci of linear and pleomorphic microcalcifications (arrows) with a segmental distribution (circled). Galactography was performed because the bloody discharge was limited to one duct. (b) Galactogram shows multiple small, irregular intraductal filling defects (arrows) secondary to neoplastic proliferation involving the same pathologic lobe that was seen at mammography.

View larger version (83K): [in this window] [in a new window] [Download PPT slide]   Figure 7.  Papilloma in a young lactating woman who presented with bloody nipple discharge. Galactogram reveals a small filling defect (arrow). Surgical biopsy showed that this finding represented a papilloma.

The mammographic appearance of galactocele depends on the amount of fat and proteinaceous material present and the density and viscosity of the fluid.

Pseudolipoma.— Pseudolipoma occurs when the fat content is very high and appears as a completely radiolucent mass.

Cystic Mass with Fat-Fluid Level.— A cystic mass with a fat-fluid level is a diagnostic sign that appears when galactoceles contain variable proportions of fat and water and the milk content is fresh. Because of the low density of the fat content and the low viscosity of fresh milk, the fat rises and the heavier water content remains in the lower portion. Obviously, this sign can be depicted only on the mediolateral mammographic view, obtained with the patient upright and with use of a horizontal beam. Although this sign can be considered pathognomonic for galactocele in the appropriate clinical setting, it can also be seen in other pathologic processes involving adipose tissue, such as fat necrosis.

Pseudohamartoma.— Pseudohamartoma also occurs when galactoceles contain variable proportions of old milk and water. The high viscosity of old milk does not allow the physical separation of fat and water, and the mass shows a mixed content closely resembling the imaging features of hamartoma (37).

At US, galactoceles can be classified as complicated cysts. Again, their appearance depends on the fat and water contents. When galactoceles are composed almost exclusively of milk, they mimic the US appearance of a benign solid tumor, manifesting as well-defined masses with posterior acoustic enhancement and highly echogenic material. Aspiration demonstrates a galactocele, thereby confirming the cystic nature of the mass and its lactic composition. Hyperechogenic-hypoechogenic fat-fluid levels can also be seen if galactoceles are composed of fresh milk. If galactoceles contain variable proportions of old milk and water–proteinaceous fluid, they appear as heterogeneous masses with mixed low and high internal echogenicity (Figs 8–10) (12,38–40).

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Pseudolipoma type galactocele. (a) Mammogram reveals an oval circumscribed mass whose radiolucency indicates a high fat content. Such a mass is mammographically indistinguishable from a true lipoma. (b) US image shows a circumscribed echogenic mass mimicking a solid lesion. Note the intense posterior enhancement (arrows), which suggests a cystic mass with a nonwater content (complicated cyst). In the appropriate clinical setting, galactocele can be suspected and can easily be confirmed with fine-needle aspiration.

View larger version (194K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Pseudolipoma type galactocele. (a) Mammogram reveals an oval circumscribed mass whose radiolucency indicates a high fat content. Such a mass is mammographically indistinguishable from a true lipoma. (b) US image shows a circumscribed echogenic mass mimicking a solid lesion. Note the intense posterior enhancement (arrows), which suggests a cystic mass with a nonwater content (complicated cyst). In the appropriate clinical setting, galactocele can be suspected and can easily be confirmed with fine-needle aspiration.

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Cystic mass with fat-fluid level galactocele. (a) Mammogram reveals an oval circumscribed mass with the characteristic fat-fluid level (arrows). In this type of galactocele, the milk content is fresh and fluid, allowing the fat to rise and the heavier water content to remain in the lower portion of the cyst. (b) US image also demonstrates the fat-fluid level (long arrows), with typical high and low echogenicity. Note that the fatty component has risen and occupies the upper (nondependent) portion of the cyst, whereas the heavier water content remains in the lower (dependent) portion. Note also the clot of fatty milk ("cream") (short arrow) floating in the nondependent portion of the cyst owing to its intermediate density.

View larger version (195K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Cystic mass with fat-fluid level galactocele. (a) Mammogram reveals an oval circumscribed mass with the characteristic fat-fluid level (arrows). In this type of galactocele, the milk content is fresh and fluid, allowing the fat to rise and the heavier water content to remain in the lower portion of the cyst. (b) US image also demonstrates the fat-fluid level (long arrows), with typical high and low echogenicity. Note that the fatty component has risen and occupies the upper (nondependent) portion of the cyst, whereas the heavier water content remains in the lower (dependent) portion. Note also the clot of fatty milk ("cream") (short arrow) floating in the nondependent portion of the cyst owing to its intermediate density.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Pseudohamartoma type galactocele. (a) Mammogram shows an oval circumscribed mass with characteristic heterogeneous density due to the presence of fat radiolucencies in the mass (arrows). (b) US image shows the mass, which consists of a mixture of hypoechogenic and hyperechogenic (*) areas.

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Pseudohamartoma type galactocele. (a) Mammogram shows an oval circumscribed mass with characteristic heterogeneous density due to the presence of fat radiolucencies in the mass (arrows). (b) US image shows the mass, which consists of a mixture of hypoechogenic and hyperechogenic (*) areas.

View larger version (168K): [in this window] [in a new window] [Download PPT slide]   Figure 11.  Infected galactocele in a young lactating woman who presented with a painful, palpable breast mass and discrete clinical signs of inflammation. US image shows a complex cystic mass. Fine-needle aspiration revealed purulent and milky material, thereby confirming the clinically suspected diagnosis (infected galactocele). Note that this US finding can be mistaken for a cavitating carcinoma.

	Inflammatory and Infectious Diseases

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Puerperal Mastitis
Infection is uncommon during pregnancy but occurs relatively often during breast-feeding. The organism that most commonly causes infection is Staphylococcus aureus, followed by Streptococcus. The source is the nursing infant’s nose and throat. The infection is due to disruption of the epithelial interface of the nipple-areola complex with retrograde dissemination of the organisms. Usually, the patient has a history of a cracked nipple or a skin abrasion. Milk stasis is an important risk factor, since stagnated milk is an excellent culture medium (35,43,44).

S aureus infections tend to be more localized and invasive from the onset, so that abscesses tend to occur more frequently, even with prompt antibiotic therapy. Conversely, Streptococcus infections often manifest as diffuse mastitis, with focal abscess formation in advanced stages (Figs 12, 13). These organisms can nearly always be cultured from milk. Antibiotic therapy given at an early stage usually controls the infection and stops abscess formation. The administration of amoxicillin-clavulanate or cloxacillin is almost always effective. The aforementioned infections correspond to the endemic or sporadic type of puerperal mastitis, which in fact accounts for the great majority of cases of mastitis. Conversely, the epidemic type of puerperal mastitis is much less common but can be life threatening and is usually related to virulent methicillin-resistant S aureus (43–45).

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Puerperal mastitis with abscess formation secondary to Streptococcus infection in a 32-year-old lactating woman with a palpable mass. (a) Mammogram shows a large lobular mass with obscured, indistinct margins (arrows) corresponding to the palpable mass. Note the diffuse signs of inflammation involving large portions of the breast. (b) US image reveals a large, complex cystic mass. Purulent material was obtained at fine-needle aspiration. The findings on both images can be mistaken for malignancy.

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Puerperal mastitis with abscess formation secondary to Streptococcus infection in a 32-year-old lactating woman with a palpable mass. (a) Mammogram shows a large lobular mass with obscured, indistinct margins (arrows) corresponding to the palpable mass. Note the diffuse signs of inflammation involving large portions of the breast. (b) US image reveals a large, complex cystic mass. Purulent material was obtained at fine-needle aspiration. The findings on both images can be mistaken for malignancy.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  Puerperal mastitis secondary to S aureus infection. (a) Transverse US image shows a complex heterogeneous mass (arrows), a finding that represents a subareolar abscess. (b) Longitudinal US image shows hypoechoic fluid collections (arrows) surrounding large subareolar ducts (periductitis).

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  Puerperal mastitis secondary to S aureus infection. (a) Transverse US image shows a complex heterogeneous mass (arrows), a finding that represents a subareolar abscess. (b) Longitudinal US image shows hypoechoic fluid collections (arrows) surrounding large subareolar ducts (periductitis).

Abscesses are commonly treated with surgical incision and drainage but can also be treated successfully with needle aspiration or catheter drainage, both under US guidance. Drainage is better performed with US guidance than with clinical excision alone, since US easily depicts the necrotic cavity, helping distinguish it from the surrounding inflammatory parenchyma. Anesthesia is required to minimize pain and to allow the introduction of a large needle, which is required for evacuation of the dense pus. Abscesses should be aspirated to dryness. The cavity should then be irrigated with local anesthetic to minimize pain and afterward with saline solution (46–48). Breast-feeding should be continued because it promotes drainage of the enlarged segment and helps resolve infection. Breast-feeding is generally not harmful to the infant when appropriate antibiotic therapy is given (35,43). Use of a breast pump is also an adequate alternative method of decompressing an infected lactating breast.

Neoplasm should be suspected and rapidly excluded in patients whose condition does not improve with antibiotic therapy. Fine-needle aspiration cytologic analysis or core biopsy is mandatory in this clinical setting.

Granulomatous Mastitis
Granulomatous mastitis is a very rare inflammatory disease of unknown cause that has been closely tied to pregnancy and lactation. It typically affects younger women, usually within 5 years of pregnancy (49–51). Inflammatory factors have been suggested as a possible cause (52,53), but a recent study isolated Corynebacterium in up to 75% of cases (54,55).

The diagnosis of granulomatous mastitis is based on exclusion, since it depends on the demonstration of a particular histologic pattern: a noncaseating, nonvasculitic granulomatous inflammatory reaction centered on lobules, combined with the exclusion of other granulomatous reactions, especially tuberculosis and fungal infections, as well as sarcoidosis, Wegener granulomatosis, and granulomatous reactions found in association with carcinomas (36,52,53).

The mammographic features are variable, ranging from normal results in patients with dense breast tissue to masses with benign or malignant features and focal asymmetric density, which in fact represent the most frequently described abnormality. The US appearance of multiple clustered, often contiguous tubular hypoechoic lesions—sometimes associated with a large, hypoechoic mass—has been considered suggestive of granulomatous mastitis (Fig 14) (51), although unfortunately, this is an uncommon manifestation whose imaging features most often resemble those of carcinoma (49–52,56,57).

View larger version (161K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.  Granulomatous mastitis in a 35-year-old woman after pregnancy. (a) US image reveals a heterogeneous hypoechoic mass with irregular margins and tubular structures (arrows) surrounded by hyperechoic boundaries. (b) Photomicrograph (original magnification, x20, H-E stain) shows lobular lymphocytic inflammatory infiltrate (arrows) with abundant multinucleate histiocytes (arrowheads). Recently, Corynebacterium has been implicated in the pathogenesis of granulomatous mastitis.

View larger version (166K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.  Granulomatous mastitis in a 35-year-old woman after pregnancy. (a) US image reveals a heterogeneous hypoechoic mass with irregular margins and tubular structures (arrows) surrounded by hyperechoic boundaries. (b) Photomicrograph (original magnification, x20, H-E stain) shows lobular lymphocytic inflammatory infiltrate (arrows) with abundant multinucleate histiocytes (arrowheads). Recently, Corynebacterium has been implicated in the pathogenesis of granulomatous mastitis.

Juvenile Papillomatosis of the Breast
An increase in the frequency of occurrence of benign proliferative disorders in pregnant or lactating patients secondary to hormone stimulation has been suggested. Juvenile papillomatosis is a distinctive and rare benign clinical-pathologic entity that characteristically involves young patients (59). Despite its epidemiologic manifestation, however, juvenile papillomatosis has not been described in association with pregnancy and lactation, perhaps due to its low frequency of occurrence. In our yet unpublished series of 18 patients, juvenile papillomatosis was found in five patients (28%) during pregnancy and lactation, all of whom presented with masses that went unrecognized prior to pregnancy. We assume that this association is more than fortuitous. In the appropriate clinical setting, juvenile papillomatosis can be suspected on the basis of its macroscopic appearance. It typically manifests as ill-defined masses composed of multiple cysts separated by firm, fibrous septa but relatively well demarcated from the normal surrounding parenchyma. At microscopy, juvenile papillomatosis is characterized by the presence of cystic and ductal hyperplasia, with papillary hyperplasia often found lining the wall of the surrounding cyst, giving the disease its most characteristic appearance (59).

At US, juvenile papillomatosis typically manifests as ill-defined hypoechoic masses that are clearly demarcated from the surrounding normal parenchyma and filled with multiple cysts of variable size. This appearance is characteristic but is nonspecific because it can be seen in other more common mastopathic and fibrous conditions. Microcalcifications can be seen at US or, more clearly, at mammography. Mammography is usually negative, sometimes demonstrating an asymmetric density. Gross examination after surgical excision is usually required to establish the diagnosis, although in our experience juvenile papillomatosis can be suspected after core biopsy (Fig 15) (60).

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.  Juvenile papillomatosis of the breast in a 33-year-old lactating woman who presented with a painless palpable mass 2 months after pregnancy. The diagnosis was based on the analysis of core biopsy specimens and was subsequently confirmed after surgical excision. (a) US image shows an irregular hypoechoic mass filled with multiple cysts of varying size, findings that are typical in juvenile papillomatosis. (b) Photomicrograph (original magnification, x5; H-E stain) of a core biopsy specimen reveals multiple cysts and varying degrees of ductal hyperplasia. Some of the cysts demonstrate hyperplastic epithelium. (c) Axial contrast-enhanced dynamic subtraction T1-weighted MR image demonstrates areas of clumped enhancement with a segmental distribution. The use of MR imaging is not recommended during lactation, but in some situations (such as this one) it can be helpful for defining disease extent. The patient underwent surgical excision after the cessation of lactation. Adequate surgical margins were obtained to avoid recurrences. Foci of malignancy, which are seen in about 10% of patients with juvenile papillomatosis (59), were excluded.

View larger version (163K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.  Juvenile papillomatosis of the breast in a 33-year-old lactating woman who presented with a painless palpable mass 2 months after pregnancy. The diagnosis was based on the analysis of core biopsy specimens and was subsequently confirmed after surgical excision. (a) US image shows an irregular hypoechoic mass filled with multiple cysts of varying size, findings that are typical in juvenile papillomatosis. (b) Photomicrograph (original magnification, x5; H-E stain) of a core biopsy specimen reveals multiple cysts and varying degrees of ductal hyperplasia. Some of the cysts demonstrate hyperplastic epithelium. (c) Axial contrast-enhanced dynamic subtraction T1-weighted MR image demonstrates areas of clumped enhancement with a segmental distribution. The use of MR imaging is not recommended during lactation, but in some situations (such as this one) it can be helpful for defining disease extent. The patient underwent surgical excision after the cessation of lactation. Adequate surgical margins were obtained to avoid recurrences. Foci of malignancy, which are seen in about 10% of patients with juvenile papillomatosis (59), were excluded.

View larger version (74K): [in this window] [in a new window] [Download PPT slide]   Figure 15c.  Juvenile papillomatosis of the breast in a 33-year-old lactating woman who presented with a painless palpable mass 2 months after pregnancy. The diagnosis was based on the analysis of core biopsy specimens and was subsequently confirmed after surgical excision. (a) US image shows an irregular hypoechoic mass filled with multiple cysts of varying size, findings that are typical in juvenile papillomatosis. (b) Photomicrograph (original magnification, x5; H-E stain) of a core biopsy specimen reveals multiple cysts and varying degrees of ductal hyperplasia. Some of the cysts demonstrate hyperplastic epithelium. (c) Axial contrast-enhanced dynamic subtraction T1-weighted MR image demonstrates areas of clumped enhancement with a segmental distribution. The use of MR imaging is not recommended during lactation, but in some situations (such as this one) it can be helpful for defining disease extent. The patient underwent surgical excision after the cessation of lactation. Adequate surgical margins were obtained to avoid recurrences. Foci of malignancy, which are seen in about 10% of patients with juvenile papillomatosis (59), were excluded.

	Benign Tumors

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Tumors Closely Related to Pregnancy and Lactation
Lactating adenoma is a benign breast lesion that is thought to occur in response to the physiologic changes that characterize pregnancy and lactation. The true nature of the tumor remains controversial. Some authors suggest that lactating adenoma is simply a variant of fibroadenoma, tubular adenoma, or lobular hyperplasia that has undergone certain histologic changes owing to the physiologic state (63–65). At histologic analysis, lactating adenomas are composed of compact aggregates of lobules that exhibit secretory hyperplasia and are separated by delicate connective tissue. At gross examination, they are well circumscribed but noncapsulated. Secretory hyperplasia in the lesion is histologically similar to the physiologic changes found in the surrounding parenchyma (63–65). Lactating adenomas characteristically regress spontaneously after pregnancy and lactation. Like fibroadenomas, lactating adenomas are prone to develop infarction (66). Curiously, the coexistence of lactating adenoma and malignancy has recently been reported (65).

Lactating adenomas usually manifest radiologically as benign masses that are indistinguishable from fibroadenomas. Radiolucent or hyperechogenic areas representing the fat content of the milk secondary to lactational hyperplasia can be seen at mammography and US, respectively, and constitute a particularly useful diagnostic sign (Fig 16). However, a few tumors can show features that can mislead from a diagnosis of malignancy, such as irregular masses, microlobulated margins, posterior acoustic shadowing, pronounced hypoechogenicity, and structural heteroechogenicity. Some of these confusing patterns may be due to infarction, as occurs in fibroadenomas (12,67–69).

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 16a.  Lactating adenoma. (a) Mammogram shows an oval circumscribed mass (arrows) with radiolucent central areas (arrowheads), some of which have a linear appearance. (b) US image demonstrates the heterogeneous echotexture of the tumor, which has central hyperechogenic areas (arrows). Both the radiolucent and the hyperechogenic areas correlate with the fat content of the milk produced by the tumor. Aspiration of milk is consistent with but not definitive for the diagnosis of galactocele; milk can also be obtained in lactating adenoma or in fibroadenoma with secretory changes. (c) Photomicrograph (original magnification, x20; Papanicolaou stain) reveals some aggregate cells (arrows) in the setting of lactational change. (d) Photomicrograph (original magnification, x40; H-E stain) of the core biopsy specimen demonstrates lactating adenoma.

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 16b.  Lactating adenoma. (a) Mammogram shows an oval circumscribed mass (arrows) with radiolucent central areas (arrowheads), some of which have a linear appearance. (b) US image demonstrates the heterogeneous echotexture of the tumor, which has central hyperechogenic areas (arrows). Both the radiolucent and the hyperechogenic areas correlate with the fat content of the milk produced by the tumor. Aspiration of milk is consistent with but not definitive for the diagnosis of galactocele; milk can also be obtained in lactating adenoma or in fibroadenoma with secretory changes. (c) Photomicrograph (original magnification, x20; Papanicolaou stain) reveals some aggregate cells (arrows) in the setting of lactational change. (d) Photomicrograph (original magnification, x40; H-E stain) of the core biopsy specimen demonstrates lactating adenoma.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 16c.  Lactating adenoma. (a) Mammogram shows an oval circumscribed mass (arrows) with radiolucent central areas (arrowheads), some of which have a linear appearance. (b) US image demonstrates the heterogeneous echotexture of the tumor, which has central hyperechogenic areas (arrows). Both the radiolucent and the hyperechogenic areas correlate with the fat content of the milk produced by the tumor. Aspiration of milk is consistent with but not definitive for the diagnosis of galactocele; milk can also be obtained in lactating adenoma or in fibroadenoma with secretory changes. (c) Photomicrograph (original magnification, x20; Papanicolaou stain) reveals some aggregate cells (arrows) in the setting of lactational change. (d) Photomicrograph (original magnification, x40; H-E stain) of the core biopsy specimen demonstrates lactating adenoma.

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 16d.  Lactating adenoma. (a) Mammogram shows an oval circumscribed mass (arrows) with radiolucent central areas (arrowheads), some of which have a linear appearance. (b) US image demonstrates the heterogeneous echotexture of the tumor, which has central hyperechogenic areas (arrows). Both the radiolucent and the hyperechogenic areas correlate with the fat content of the milk produced by the tumor. Aspiration of milk is consistent with but not definitive for the diagnosis of galactocele; milk can also be obtained in lactating adenoma or in fibroadenoma with secretory changes. (c) Photomicrograph (original magnification, x20; Papanicolaou stain) reveals some aggregate cells (arrows) in the setting of lactational change. (d) Photomicrograph (original magnification, x40; H-E stain) of the core biopsy specimen demonstrates lactating adenoma.

View larger version (158K): [in this window] [in a new window] [Download PPT slide]   Figure 17a.  Growing fibroadenoma. (a) US image obtained in a 32-year-old pregnant woman reveals a fibroadenoma with a prominent ductal pattern (arrows). Gestational fibroadenomas may undergo proliferative changes under hormonal stimulation, leading to manifestations resembling those of complex fibroadenomas. (b) Transverse US images obtained in a 28-year-old pregnant woman show a fibroadenoma containing large cysts (arrows). (c) Color Doppler US image obtained in a 38-year-old pregnant woman shows a fibroadenoma with increased vascularity.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 17b.  Growing fibroadenoma. (a) US image obtained in a 32-year-old pregnant woman reveals a fibroadenoma with a prominent ductal pattern (arrows). Gestational fibroadenomas may undergo proliferative changes under hormonal stimulation, leading to manifestations resembling those of complex fibroadenomas. (b) Transverse US images obtained in a 28-year-old pregnant woman show a fibroadenoma containing large cysts (arrows). (c) Color Doppler US image obtained in a 38-year-old pregnant woman shows a fibroadenoma with increased vascularity.

View larger version (226K): [in this window] [in a new window] [Download PPT slide]   Figure 17c.  Growing fibroadenoma. (a) US image obtained in a 32-year-old pregnant woman reveals a fibroadenoma with a prominent ductal pattern (arrows). Gestational fibroadenomas may undergo proliferative changes under hormonal stimulation, leading to manifestations resembling those of complex fibroadenomas. (b) Transverse US images obtained in a 28-year-old pregnant woman show a fibroadenoma containing large cysts (arrows). (c) Color Doppler US image obtained in a 38-year-old pregnant woman shows a fibroadenoma with increased vascularity.

Fibroadenoma with Infarction.— Spontaneous infarction of the breast is a very unusual phenomenon that usually appears in association with pregnancy and lactation. Infarction may develop in lactating nontumoral glandular parenchyma or may involve tumors per se. It is recognized that fibroadenomas and lactating adenomas can develop foci of infarction during pregnancy. This phenomenon is usually detected in the 3rd trimester or after delivery and can be clinically suspected if sudden pain occurs in a previously painless fibroadenoma. Intravascular thrombosis has been detected in some infarcted lesions and has been suggested as a causative factor. The architectural and pathologic appearance of fibroadenoma varies depending on the severity of infarction. It is not surprising, therefore, that the radiologic features of fibroadenomas can change, with more lobulated margins, a heterogeneous echotexture, and acoustic shadowing (Figs 18, 19). If large infarcts occur, the tumor may show suspicious findings requiring histologic analysis. In this setting, the definitive diagnosis can easily be established with core biopsy (36,73–75).

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 18a.  Fibroadenoma with infarction in a nonlactating 35-year-old woman who presented with sudden pain and swelling in the upper portion of the left breast 4 months after delivery. (a) Baseline US image obtained at the time of diagnosis before pregnancy reveals an oval, slightly lobulated mass with circumscribed margins. Note the posterior acoustic enhancement (arrows). (b) US image reveals a round heterogeneous mass with irregular margins representing an infarcted fibroadenoma. Note the posterior acoustic shadowing (arrows). (c) Photomicrograph (original magnification, x10; H-E stain) shows the fibroadenoma with large areas of hyalinization (*) secondary to infarction. The suspicious US findings led to excision of the mass, which proved to be infarcted fibroadenoma.

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 18b.  Fibroadenoma with infarction in a nonlactating 35-year-old woman who presented with sudden pain and swelling in the upper portion of the left breast 4 months after delivery. (a) Baseline US image obtained at the time of diagnosis before pregnancy reveals an oval, slightly lobulated mass with circumscribed margins. Note the posterior acoustic enhancement (arrows). (b) US image reveals a round heterogeneous mass with irregular margins representing an infarcted fibroadenoma. Note the posterior acoustic shadowing (arrows). (c) Photomicrograph (original magnification, x10; H-E stain) shows the fibroadenoma with large areas of hyalinization (*) secondary to infarction. The suspicious US findings led to excision of the mass, which proved to be infarcted fibroadenoma.

View larger version (162K): [in this window] [in a new window] [Download PPT slide]   Figure 18c.  Fibroadenoma with infarction in a nonlactating 35-year-old woman who presented with sudden pain and swelling in the upper portion of the left breast 4 months after delivery. (a) Baseline US image obtained at the time of diagnosis before pregnancy reveals an oval, slightly lobulated mass with circumscribed margins. Note the posterior acoustic enhancement (arrows). (b) US image reveals a round heterogeneous mass with irregular margins representing an infarcted fibroadenoma. Note the posterior acoustic shadowing (arrows). (c) Photomicrograph (original magnification, x10; H-E stain) shows the fibroadenoma with large areas of hyalinization (*) secondary to infarction. The suspicious US findings led to excision of the mass, which proved to be infarcted fibroadenoma.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 19a.  Fibroadenoma with secretory hyperplasia and infarction in a nonlactating 42-year-old woman who presented with a painful, palpable mass 4 months after delivery. (a) Mammogram reveals a round circumscribed mass (dashed circle) with multiple suspect microcalcifications corresponding to the hyperplastic epithelium of secretory change. Within the solid circle is a magnified view of the mass. (b) Color Doppler US image shows a complex mass with a large cystic area (short arrows) corresponding to the infarcted or necrotic region and a solid area with increased vascularity (long arrows). The diagnosis was established with core biopsy and subsequently confirmed at surgical excision.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 19b.  Fibroadenoma with secretory hyperplasia and infarction in a nonlactating 42-year-old woman who presented with a painful, palpable mass 4 months after delivery. (a) Mammogram reveals a round circumscribed mass (dashed circle) with multiple suspect microcalcifications corresponding to the hyperplastic epithelium of secretory change. Within the solid circle is a magnified view of the mass. (b) Color Doppler US image shows a complex mass with a large cystic area (short arrows) corresponding to the infarcted or necrotic region and a solid area with increased vascularity (long arrows). The diagnosis was established with core biopsy and subsequently confirmed at surgical excision.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 20.  Fibroadenoma with lactational change 3 months after delivery in a 33-year-old woman. US image shows a round, heterogeneous circumscribed mass with mixed hypoechoic and hyperechoic areas. The hyperechogenic punctate central areas represent calcifications. Note also the posterior acoustic shadowing.

	Malignant Tumors

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Patients with PABC tend to have larger, more advanced neoplasms at diagnosis and a poorer outcome than do other women of the same age with breast carcinoma. More than 50% of patients present with high-grade tumors (1,35,77). High rates of inflammatory tumors have also been reported. In addition, more than 50% of patients present with lymph node involvement. The high prevalence of hormone-receptor–negative and HER2/neu–positive tumors supports their aggressive biologic growth pattern (1,77). Prognosis is poor, a fact that is thought to be partly explained by a tendency of pregnant patients to present at a more advanced stage than nonpregnant women. However, certain studies have found that pregnancy itself may be an independent predictor of worse prognosis. Worse prognosis likely results from a combination of delayed diagnosis and a more aggressive growth pattern due to the biologic effects of pregnancy. Recurrences are common and usually appear within 2–3 years of diagnosis (1,35,77).

Patients with PABC almost always present with a palpable mass. Swelling, erythema, and diffuse breast enlargement are less common features that suggest locally advanced carcinoma (1,35,77). The radiologic features of PABC do not differ from those of non-PABC. Mammographic sensitivity for PABC is lower in pregnant or lactating patients due to increased glandular density. As previously stated, US constitutes the most appropriate radiologic method for assessing PABC (8–13). US is also useful in assessing axillary nodes and monitoring the response to neoadjuvant chemotherapy (13). Nevertheless, mammography plays a complementary role in the evaluation of these patients and must always be performed if cancer is suspected, since it can demonstrate features such as malignant microcalcifications, multifocality, multicentricity, or bilaterality that may not be suspected at US alone (Figs 21, 22) (8–13).

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 21a.  Inflammatory carcinoma during the 3rd trimester of pregnancy in a 35-year-old woman. (a) Mammogram shows a marked diffuse increase in parenchymal density with skin thickening (long arrows) and thickened trabeculae due to dilated lymphatic vessels (short arrows), the hallmarks of inflammatory carcinoma. (b) US image shows skin thickening (short arrows) and a network of hypoechoic and anechoic tubular structures (long arrows) representing enlarged lymphatic vessels. Note also the diffuse increase in parenchymal echogenicity (*). US can usually help guide biopsy if a mass is seen at US or if results of skin punch biopsy are nondiagnostic.

View larger version (181K): [in this window] [in a new window] [Download PPT slide]   Figure 21b.  Inflammatory carcinoma during the 3rd trimester of pregnancy in a 35-year-old woman. (a) Mammogram shows a marked diffuse increase in parenchymal density with skin thickening (long arrows) and thickened trabeculae due to dilated lymphatic vessels (short arrows), the hallmarks of inflammatory carcinoma. (b) US image shows skin thickening (short arrows) and a network of hypoechoic and anechoic tubular structures (long arrows) representing enlarged lymphatic vessels. Note also the diffuse increase in parenchymal echogenicity (*). US can usually help guide biopsy if a mass is seen at US or if results of skin punch biopsy are nondiagnostic.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 22a.  PABC in a nonlactating 38-year-old woman who presented with a large mass in the right breast 2 months after delivery. (a) Mammogram reveals a large lobular mass with obscured margins (arrows), although the mass is partially circumscribed. Note the suspect axillary node (*). (b) US image shows an irregular heterogeneous hypoechoic mass with indistinct margins (arrows) representing a histologically high-grade invasive ductal carcinoma.

View larger version (166K): [in this window] [in a new window] [Download PPT slide]   Figure 22b.  PABC in a nonlactating 38-year-old woman who presented with a large mass in the right breast 2 months after delivery. (a) Mammogram reveals a large lobular mass with obscured margins (arrows), although the mass is partially circumscribed. Note the suspect axillary node (*). (b) US image shows an irregular heterogeneous hypoechoic mass with indistinct margins (arrows) representing a histologically high-grade invasive ductal carcinoma.

View larger version (157K): [in this window] [in a new window] [Download PPT slide]   Figure 23a.  Medullary carcinoma in an asymptomatic nonlactating 38-year-old BRCA1 mutation carrier. The diagnosis was made with screening US 6 months after delivery. (a) US image reveals an 8-mm round circumscribed mass. The mass was not palpable and could not be visualized at mammography. (b) Photomicrograph (original magnification, x20; H-E stain) shows a medullary carcinoma with the characteristic histologically high-grade appearance. Several studies have found a high prevalence of medullary carcinomas in BRCA1 mutation carriers.

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 23b.  Medullary carcinoma in an asymptomatic nonlactating 38-year-old BRCA1 mutation carrier. The diagnosis was made with screening US 6 months after delivery. (a) US image reveals an 8-mm round circumscribed mass. The mass was not palpable and could not be visualized at mammography. (b) Photomicrograph (original magnification, x20; H-E stain) shows a medullary carcinoma with the characteristic histologically high-grade appearance. Several studies have found a high prevalence of medullary carcinomas in BRCA1 mutation carriers.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 24a.  Microglandular adenosis in a nonlactating 27-year-old BRCA1 mutation carrier who presented with a palpable mass 6 months after delivery. (a) US image obtained directly over the lesion shows a 10-mm lobular mass with irregular margins at the anterior surface of the gland. (b) Photomicrograph (original magnification, x20; H-E stain) of the core biopsy specimen reveals poorly circumscribed nonlobulocentric proliferation of small glands surrounded by adipocytes. Results of mammography were negative. The diagnosis of microglandular adenosis was subsequently confirmed at surgical excision, and foci of malignancy were excluded. The latter finding has been reported in up to 23% of patients in the literature (82).

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 24b.  Microglandular adenosis in a nonlactating 27-year-old BRCA1 mutation carrier who presented with a palpable mass 6 months after delivery. (a) US image obtained directly over the lesion shows a 10-mm lobular mass with irregular margins at the anterior surface of the gland. (b) Photomicrograph (original magnification, x20; H-E stain) of the core biopsy specimen reveals poorly circumscribed nonlobulocentric proliferation of small glands surrounded by adipocytes. Results of mammography were negative. The diagnosis of microglandular adenosis was subsequently confirmed at surgical excision, and foci of malignancy were excluded. The latter finding has been reported in up to 23% of patients in the literature (82).

Burkitt lymphoma of the breast is a specific and very rare clinical manifestation of the disease that usually affects pregnant or postpartum patients with massive enlargement of both breasts. It has classically manifested as the endemic type, affecting young, pregnant African women; however, it can also be seen in Caucasian women in the sporadic form. Burkitt lymphoma of the breast is characterized by rapid spread and a poor prognosis, although spontaneous regression upon cessation of lactation has also been described. Breast involvement is almost always bilateral. At mammography, Burkitt lymphoma of the breast characteristically manifests with a bilateral and diffuse marked increase in parenchymal density, a finding that correlates well with the aggressive and infiltrative nature of the tumor (Fig 25). Massive bilateral involvement of the ovaries is common, and tumors may develop in any of the abdominal organs, especially the liver, spleen, and kidneys. Peripheral lymph node involvement is rare (83–86).

View larger version (62K): [in this window] [in a new window] [Download PPT slide]   Figure 25a.  Pregnancy-related Burkitt lymphoma of the breast in a 29-year-old woman who presented with painful and rapid diffuse enlargement of both breasts 2 months after delivery. (a, b) Mediolateral oblique mammograms reveal a marked diffuse increase in parenchymal density in both breasts. (c) Photomicrograph (original magnification, x100; H-E stain) of the core biopsy specimen demonstrates Burkitt lymphoma.

View larger version (69K): [in this window] [in a new window] [Download PPT slide]   Figure 25b.  Pregnancy-related Burkitt lymphoma of the breast in a 29-year-old woman who presented with painful and rapid diffuse enlargement of both breasts 2 months after delivery. (a, b) Mediolateral oblique mammograms reveal a marked diffuse increase in parenchymal density in both breasts. (c) Photomicrograph (original magnification, x100; H-E stain) of the core biopsy specimen demonstrates Burkitt lymphoma.

View larger version (205K): [in this window] [in a new window] [Download PPT slide]   Figure 25c.  Pregnancy-related Burkitt lymphoma of the breast in a 29-year-old woman who presented with painful and rapid diffuse enlargement of both breasts 2 months after delivery. (a, b) Mediolateral oblique mammograms reveal a marked diffuse increase in parenchymal density in both breasts. (c) Photomicrograph (original magnification, x100; H-E stain) of the core biopsy specimen demonstrates Burkitt lymphoma.

	Conclusions

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Tumors and diseases affecting the breast during pregnancy and lactation are primarily the same as those observed in nonpregnant women. However, the appearance of some features may change during pregnancy and lactation. Knowledge of these different appearances and of certain unique entities that are specifically related to pregnancy and lactation can help the radiologist make the diagnosis. Delayed diagnosis is the major cause of the more advanced stage and the worse prognosis commonly found in pregnant or lactating patients with breast carcinoma.

	Acknowledgments

 
The authors wish to thank our secretaries, Isabel Alvarez and Ester Casado; our radiographer, Elisenda Mestres; and our nurse, Montser-rat Valdearcos, for their expert assistance in daily clinical practice; and Carolyn Newey and Pablo Ayesta for their editorial support.

	Footnotes

 

Abbreviations: ACR = American College of Radiology, H-E = hematoxylin-eosin, PABC = pregnancy-associated breast carcinoma

	References

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