【孕期及哺乳期乳腺影像】

Radiologic Evaluation of Breast Disorders Related to Pregnancy and Lactation1 1. Josep M. Sabate, MD, 2. Montse Clotet, MD, 3. Sofia Torrubia, MD, 4. Antonio Gomez, MD, 5. Ruben Guerrero, MD, 6. Pilar de Las Heras, MD and 7. Enrique Lerma, MD + Author Affiliations 1. 1From 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. 1. Address correspondence to J.M.S. (e-mail: Jsabate@santpau.es).   Next Section Abstract 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 · ACR = American College of Radiology · H-E = hematoxylin-eosin · PABC = pregnancy-associated breast carcinoma Previous SectionNext Section LEARNING OBJECTIVES 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. Previous SectionNext Section Introduction 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. View this table: · In this window · In a new window Breast Disorders Related to Pregnancy and Lactation Previous SectionNext Section Physiologic Changes during Pregnancy and Lactation 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). View larger version: · In this page · In a new window · Download as PowerPoint Slide Figure 1a.  (a, b) Pathologic changes during pregnancy (gestational hyperplasia). (a) Photomicrograph (original magnification, ×20; 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, ×40; 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, ×40; 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: · In this page · In a new window · Download as PowerPoint Slide Figure 1b.  (a, b) Pathologic changes during pregnancy (gestational hyperplasia). (a) Photomicrograph (original magnification, ×20; 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, ×40; 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, ×40; 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: · In this page · In a new window · Download as PowerPoint Slide Figure 1c.  (a, b) Pathologic changes during pregnancy (gestational hyperplasia). (a) Photomicrograph (original magnification, ×20; 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, ×40; 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, ×40; 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 (*). 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). Previous SectionNext Section Radiologic Evaluation of the Breast during Pregnancy and Lactation: State of the Art 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: · In this page · In a new window · Download as PowerPoint 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: · In this page · In a new window · Download as PowerPoint 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. 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). View larger version: · In this page · In a new window · Download as PowerPoint 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: · In this page · In a new window · Download as PowerPoint 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: · In this page · In a new window · Download as PowerPoint 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: · In this page · In a new window · Download as PowerPoint 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. 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). Previous SectionNext Section Medicolegal Issues 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 fistu