DOI: 10.1148/rg.27si075505
RadioGraphics 2007;27:S101-S124
© RSNA, 2007
Radiologic Evaluation of Breast Disorders Related to Pregnancy and Lactation1
Josep M. Sabate, MD,
Montse Clotet, MD,
Sofia Torrubia, MD,
Antonio Gomez, MD,
Ruben Guerrero, MD,
Pilar de Las Heras, MD, and
Enrique Lerma, MD
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).
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Abstract
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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
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LEARNING OBJECTIVES
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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.
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Introduction
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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.
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Physiologic Changes during Pregnancy and Lactation
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During pregnancy, the breast undergoes numerous changes in preparation for lactation. These changes occur in response to an increase in circulating hormones—basically estrogen, progesterone, and prolactin—and begin early in the 2nd month of the 1st trimester of pregnancy. This initial period of change occurs under predominantly estrogenic influence and is characterized by (a) marked ductular sprouting with some branching and discrete lobular growth; (b) simultaneous involution of the fibrofatty stroma; and (c) an increase in glandular vascularity, often accompanied by infiltration by mononuclear cells (Fig 1a).
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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 (*).
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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 (*).
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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 (*).
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The 2nd and 3rd trimesters are characterized by marked lobular growth with great cellular proliferation accompanied by a relative stromal decrease. This epithelial proliferation shows dramatic cellular enlargement with pronounced cytologic changes, most marked in the lobular unit, and is caused mainly by progesterone. The current alveolar cells differentiate into a more specialized colostrum-cell epithelium and prolactin initiates protein synthesis, but the colostrum does not yet contain milk because, during pregnancy, progesterone antagonizes the effect and synthesis of prolactin (lactogenesis I) (Fig 1b).
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).
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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.
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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.
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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.
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US constitutes the most appropriate radiologic method for evaluating breast disorders in women during pregnancy and lactation. US has a greater sensitivity (nearly 100%) than mammography in the evaluation of patients with carcinoma (9,10).Over 90% of women with PABC present with breast masses, which are easily evaluated with US. In addition, US easily helps detect whether the palpable area represents a true mass or normal parenchyma. During pregnancy, the breast parenchyma is characterized by enlargement of the nonfatty fibroglandular component with slight diffuse hypoechogenicity (Fig 3). In contrast, during lactation, the parenchyma shows diffuse hyperechogenicity, a prominent ductal system, and increased vascularity (Fig 4) (8–12).
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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.
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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.
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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.
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The routine use of magnetic resonance (MR) imaging in the evaluation and treatment of pregnant patients is not appropriate. The MR imaging assessment of malignant neoplasms during lactation is controversial and difficult because lactational parenchyma, in contrast with normal non-lactational tissue, shows rapid enhancement following the intravenous administration of contrast material, followed by an early plateau of enhancement. In contrast, due to the increased fraction of mobile water in milk, during lactation the breast parenchyma has diffuse high signal intensity on T2-weighted images, a finding that allows more reliable visualization of tumors with this sequence (15,16).
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).
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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).
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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).
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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.
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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.
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Microcalcifications secondary to gestational or secretory hyperplasia must be distinguished clinically from a different entity known as pregnancy-like hyperplasia or pseudolactational hyperplasia, which manifests with the same radiologicpathologic findings in nonpregnant, nonlactating women. Carcinomas arising from preexisting pregnancy-like hyperplastic lesions have been described; to date, however, malignant potentiality has not been described in secretory or lactational hyperplasia (31).
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).
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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.
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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.
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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.
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Galactocele
Galactoceles are the most common benign breast lesions in lactating women, although they more frequently occur after cessation of breast-feeding, when milk is retained and becomes stagnant within the breast (12,35). Galactoceles are cysts composed of cuboidal or flat epithelium containing fluid that resembles milk. They are often accompanied by inflammatory or necrotic debris. Biochemical analysis of the material aspirated from galactoceles shows wide variation in the proportions of proteins, fat, and lactose. The cysts form as a result of duct dilatation and are frequently encompassed by a fibrous wall of varying thickness that can be associated with an inflammatory component. Chronic inflammation and fat necrosis can be seen due to cyst leakage (36). Aspiration is both diagnostic and therapeutic, yielding fluid milk when performed during lactation and more thickened milk fluid when obtained from older lesions after lactation has ended (35,37).
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).
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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.
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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.
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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.
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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.
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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.
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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.
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Infection represents a relatively common and not unexpected complication of galactoceles due to their rich nutrient content. An infected galactocele is usually clinically suspected and is easily confirmed with fine-needle aspiration when mixed purulent and milky material is obtained. Its US features differ in that they are more conspicuous (Fig 11).
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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.
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Gigantomastia
Gigantomastia is a very rare condition that complicates about one of every 100,000 pregnancies. It is characterized by massive enlargement of the breasts, resulting in tissue necrosis, ulceration, infection, and hemorrhage, complications that can be life threatening in certain cases. Although its cause remains unknown, gigantomastia is believed to represent an abnormal response to hormonal stimulation during pregnancy. Both glands grow dramatically, and weights of 4–6 kg per breast have been reported, resulting in dyspnea. The diagnosis of gigantomastia is based on clinical findings, and radiologic studies are not required if no associated disorders are present. Pathologic procedures are not usually required and, if performed, yield findings that resemble those in fibroadenoma (35). Treatment is based on bromocriptine administration, but surgical intervention (reduction mammoplasty or simple mastectomy with posterior reconstruction) is required if the disorder progresses (35,41,42).
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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).
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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.
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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.
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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).
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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).
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Mammography is not usually required in lactational mastitis unless malignancy is suspected. No significant abnormalities are usually found, although in severe mastitis, skin and trabecular thickening from breast edema can be depicted. Abscesses can manifest as suspect, ill-defined masses. US plays an important role in the diagnosis and treatment of mastitis if abscess formation is suspected. Abscesses usually manifest as irregular hypoechoic or anechoic masses, sometimes with fluid-debris levels and posterior acoustic enhancement. The inflammatory noncavitated parenchyma manifests as an ill-defined, hypoechoic surrounding mass. More subacute forms of lactational mastitis may show findings of periductitis (46,47).
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).
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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.
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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.
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Granulomatous mastitis generally manifests as a distinct firm to hard mass that may involve any part of the breast but tends to spare the subareolar regions. Reactive lymphadenopathy may be present in up to 15% of patients. The prognosis is often good, but local recurrence has been reported. Corticotherapy has proved effective. Primary treatment has classically been based on excisional biopsy (48–52,56,57), but close surveillance without surgery has also proved adequate in the management of cases involving spontaneous resolution (58). If Corynebacterium is isolated with microbiologic or pathologic studies, antibiotic therapy based on the administration of penicillin and tetracycline should be effective (54,55).
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).
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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.
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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.
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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.
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Treatment is based on surgical excision, with completely negative margins required to avoid local recurrence. Radiologists should be aware of juvenile papillomatosis because it has been reported to be associated with carcinoma in up to 15% of cases. In addition, strict follow-up of female relatives is mandatory, since carcinomas have been found in nearly 50% of cases (59,61, 62). Therefore, juvenile papillomatosis can be considered a potential risk factor for breast carcinoma in young people.
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Benign Tumors
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Abstract
LEARNING OBJECTIVES
