(Radiology. 2000;217:247-250.)
© RSNA, 2000
New Bilateral Microcalcifications at Mammography in a Postlactational Woman: Case Report1
Daniel T. Stucker, MD,
Debra M. Ikeda, MD,
Anne-Renee Hartman, MD,
Tracy I. George, MD,
Kent W. Nowels, MD,
Sandra L. Birdwell, MD,
Don Goffinet, MD and
Robert W. Carlson, MD
1 From the Departments of Radiology (D.T.S., D.M.I.), Medical Oncology (A.R.H., R.W.C.), Pathology (T.I.G., K.W.N.), and Radiation Oncology (S.L.B., D.G.), Stanford University Hospital, 300 Pasteur Dr, Stanford, CA 94305. Received September 24, 1999; revision requested December 15; revision received February 17, 2000; accepted March 7. Address correspondence to D.M.I.
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ABSTRACT
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A 33-year-old woman with a strong family history of breast cancer who was referred for mammography 5 weeks after completing lactation was found to have new diffuse bilateral microcalcifications in the breast ducts. Contrast material–enhanced magnetic resonance imaging of the breast showed bilateral patchy areas of abnormal enhancement. Large-core needle biopsy showed diffuse calcifications within expanded benign ducts in a background of lactational change, without evidence of malignancy. To the authors’ knowledge, these calcifications have not been previously reported and are possibly related to milk stasis or apoptosis associated with lactation.
Index terms: Breast, biopsy, 00.1261 • Breast, calcification, 00.54, 00.811 • Breast, lactation, 00.8119 • Breast, MR, 00.121411, 00.121417, 00.12143 • Breast, US, 00.12981 • Breast radiography, 00.11, 00.113
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INTRODUCTION
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Breast cancer is the most frequently diagnosed cancer during pregnancy, often detected as a palpable mass, pleomorphic calcifications, or a spiculated mass at mammography (1,2). We present a case of a recently lactating woman with a strong family history of breast cancer whose new, bilateral, regional microcalcifications at mammography resulted in a diagnostic dilemma but were benign at biopsy.
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Case Report
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The patient was a 33-year-old woman whose mother and maternal grandmother both had unilateral breast cancer at 39 and 46 years of age, respectively. Because of her family history, a baseline mammogram was obtained at age 30 years; it showed dense breast tissue, no features of malignancy, and no calcifications. One year later, she had an uncomplicated pregnancy and subsequently breast fed her child for 1 year. After the 1st month of breast feeding, she noted a thickening in the upper outer quadrant of her left breast. Physical examination by her referring physician revealed multiple, palpable, bilateral breast nodules all measuring less than 1 centimeter. Breast ultrasonography (US) demonstrated numerous, bilateral, simple, fluid-filled cavities, representing cysts and dilated ducts, without discrete solid masses. One week later, she developed bilateral obstructed milk ducts, which recurred in various ductal patterns approximately once per week during the next 11 months; each recurrence was resolved with the use of hot compresses and continuation of breast feeding. A single episode of acute mastitis in the upper outer quadrant of the left breast was successfully treated with dicloxacillin sodium. After completion of breast feeding, a physical examination revealed no palpable masses, skin changes, nipple retraction, or suggestive adenopathy. A mammogram was obtained 5 weeks after completion of lactation and prior to an attempt at a second pregnancy.
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Imaging and Histopathologic Findings
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Mammograms showed new bilateral diffuse, scattered, and occasionally clustered microcalcifications in regional distributions in both breasts, with a predominance in the left lower inner quadrant. There were no associated masses, breast edema, architectural distortion, or lymphadenopathy. Magnification views showed innumerable round and punctate calcifications that were mostly scattered and showed round calcifications in occasional linear and linear branching patterns within the most concentrated areas of calcifications in the left breast and a linear form in the right breast, which suggested the calcifications might be within the breast ducts (Fig 1). Bilateral real-time US performed with a 7.5-MHz linear-array transducer showed no discrete cystic or solid masses. To determine if the calcifications were in the ducts, magnification specimen radiographs of the patient’s milk were obtained and showed multiple round and punctate microcalcifications similar to those depicted on the mammogram (Fig 2).
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Figure 1a. (a). Paired, cropped craniocaudal magnification mammograms of both breasts show innumerable new microcalcifications (arrows) regionally distributed in both inner and outer quadrants. (b) Cropped lateral-medial magnification mammogram of the lower left breast shows innumerable round, punctate calcifications representative of those in both breasts, with a few in a linear branching pattern (arrows). (c) Cropped lateral-medial magnification mammogram of the lower right breast and (d) photographically magnified craniocaudal mammogram of the medial right breast show new calcifications with one linear form (arrow).
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Figure 1b. (a). Paired, cropped craniocaudal magnification mammograms of both breasts show innumerable new microcalcifications (arrows) regionally distributed in both inner and outer quadrants. (b) Cropped lateral-medial magnification mammogram of the lower left breast shows innumerable round, punctate calcifications representative of those in both breasts, with a few in a linear branching pattern (arrows). (c) Cropped lateral-medial magnification mammogram of the lower right breast and (d) photographically magnified craniocaudal mammogram of the medial right breast show new calcifications with one linear form (arrow).
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Figure 1c. (a). Paired, cropped craniocaudal magnification mammograms of both breasts show innumerable new microcalcifications (arrows) regionally distributed in both inner and outer quadrants. (b) Cropped lateral-medial magnification mammogram of the lower left breast shows innumerable round, punctate calcifications representative of those in both breasts, with a few in a linear branching pattern (arrows). (c) Cropped lateral-medial magnification mammogram of the lower right breast and (d) photographically magnified craniocaudal mammogram of the medial right breast show new calcifications with one linear form (arrow).
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Figure 1d. (a). Paired, cropped craniocaudal magnification mammograms of both breasts show innumerable new microcalcifications (arrows) regionally distributed in both inner and outer quadrants. (b) Cropped lateral-medial magnification mammogram of the lower left breast shows innumerable round, punctate calcifications representative of those in both breasts, with a few in a linear branching pattern (arrows). (c) Cropped lateral-medial magnification mammogram of the lower right breast and (d) photographically magnified craniocaudal mammogram of the medial right breast show new calcifications with one linear form (arrow).
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Physical examination of the breast revealed normal findings and no focal masses in the regions of the calcifications or elsewhere. Hypercalcemia and hyperparathyroidism were excluded on the basis of normal levels of serum calcium and parathyroid hormone. The bilateral nature of the round calcifications suggested a benign cause, and the presence of calcifications in the patient’s breast milk confirmed that some of the calcifications were in the breast ducts and were possibly related to her recent cessation of breast feeding. However, the ductal distribution pattern of the calcifications, despite their bilateral nature, and their new development also suggested the possibility of ductal carcinoma in situ, although the development of extensive bilateral ductal carcinoma in situ to the extent seen in this patient would be rare.
Contrast material-enhanced magnetic resonance (MR) imaging was performed to determine if there were any signs of invasive breast cancer. The MR imaging parameters included performance of a 2-minute dynamic spiral sequence during a bolus injection of 1 millimole per kilogram of gadolinium-based contrast medium (Magnevist; Berlex, Wayne, NJ) per kilogram of body weight to identify regions of contrast medium washout and to generate time–signal-intensity curves by using a previously reported method (3).
The spiral dynamic sequence consisted of eight spiral interleaves, such that 12 sections could be obtained through the breast within 7.68 seconds at a resolution of 7-10 mm, depending on the breast size (960/6.8 [repetition time msec/echo time msec]; field of view, 20cm; matrix, 188 x 188; flip angle, 90°; one signal acquired).
Initially and again at 8–12 minutes after the injection, a high-spatial-resolution three-dimensional spectral spatial magnetization transfer pulse sequence with 1.5-mm-thick sections was performed (4). MR images were obtained with a three-dimensional gradient-recalled-echo pulse sequence with water-selective spectral-spatial excitation for fat nulling and an on-resonance 1-2-1 binomial magnetization transfer pulse for suppression of fibroglandular tissue (56/9; fat-nulled 3D volume-excitation gradient-echo sequence; flip angle, 80°; 60-section volume with 1.5–2.0-mm-thick partitions; matrix, 512 x 192; field of view, 20 cm)
High-spatial-resolution MR images showed patchy heterogeneous abnormal enhancement throughout both breasts, most prominent in the lower inner and upper outer quadrants of the left breast (Fig 3). Similar, but less prominent enhancement was noted in the right breast, particularly in the lower inner and lower outer quadrants.
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Figure 3a. Sagittal contrast-enhanced three-dimensional spectral spatial magnetization transfer MR images of the (a) left and (b) right breasts show patchy regions of heterogeneous contrast enhancement (arrows) that correspond to regions of calcification on the mammograms.
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Figure 3b. Sagittal contrast-enhanced three-dimensional spectral spatial magnetization transfer MR images of the (a) left and (b) right breasts show patchy regions of heterogeneous contrast enhancement (arrows) that correspond to regions of calcification on the mammograms.
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Postprocessing of the time–signal-intensity curves obtained with the images showed slow initial enhancement and continued progressive enhancement over time in all abnormally enhanced regions; these curves were more characteristic of a benign cause than of a cancerous one (3,5).
Because of the possibility of ductal carcinoma in situ, percutaneous stereotactic vacuum-assisted multidirectional 11-gauge large-core needle biopsy was performed 10 days after mammography. Biopsies were performed in the left upper outer quadrant, left lower inner quadrant, right lower inner quadrant and right lower outer quadrant; regions corresponded to those with the greatest concentration of calcifications on the mammograms and the most enhanced regions on MR images. Calcifications were identified on the core biopsy specimen radiographs in all biopsied areas.
Histopathologic findings revealed that the calcifications were large, globular, smoothly contoured and coarse in appearance. Eosinophilic and granular secretory material was present in ducts and was admixed with the microcalcifications. These findings were compatible with lactational change, with breast epithelium showing an increased number of acini per lobule and lined by epithelium containing abundant vacuolated cytoplasm and round nuclei with enlarged round nucleoli. The intralobular stroma was infiltrated by numerous lymphocytes, plasma cells, and scattered macrophages. There was no evidence of atypical hyperplasia, in situ carcinoma, or invasive carcinoma. The findings were interpreted as a lactational change with extensive calcifications associated with benign ducts and chronic periductal mastitis (Fig 4).
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Figure 4. Representative photomicrograph of a percutaneous core biopsy specimen shows calcifications (straight arrows) without malignant features within a benign-appearing, expanded duct. Dilated ducts contain microcalcifications, degenerating cells, and granular secretory material (curved arrow); are lined with ductal epithelium showing lactational change; and are adjacent to intralobular stroma with chronic inflammatory cells. (Hematoxylin-eosin stain; original magnification, x20.)
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Discussion
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To our knowledge, this is the first report of a mammogram showing new bilateral breast calcifications associated with recent pregnancy and cessation of lactation. Round bilateral calcifications distributed throughout both breasts usually suggest benign entities (6,7), but their new bilateral development, as seen in our postlactational patient, is exceedingly unusual. Although it is possible that the calcifications were not new but conceivably developed at any time during the 3-year period between mammograms, the clinical history, histopathologic results, and calcifications in our patient’s milk suggest that the calcifications were probably related to lactation.
Calcifications may reflect a product of a living cell or a degenerative process (8) and can be present in malignancy, particularly ductal carcinoma in situ (9–11). But, in general, calcifications are not a common mammographic feature of the lactational or postlactational breast. The pathogenesis of the calcifications in this patient were unclear but may relate to apoptosis. Pituitary apoptosis is reported with termination of lactation (12), and apoptosis occurs with breast involution (13). Milk accumulation or stasis in the ducts may also induce programmed cell death (14,15). The admixture of secretory material with calcifications in benign ducts in this patient supports the hypothesis that the calcifications were due to inspissated secretions undergoing calcific change. Whether the calcifications were also related to apoptosis is unknown.
Usually, benign-appearing diffuse bilateral calcifications are due to a benign cause such as fibrocystic change or sclerosing adenosis (6). The appearance of numerous, extensive, primarily benign-appearing findings in both breasts are commonly benign. In our patient, the development of calcifications between mammograms and their occasional ductal distribution were of concern despite their bilateral nature and despite the benign time-signal-intensity curves obtained with MR images, given her family history of breast cancer in premenopausal relatives. Ductal carcinoma in situ associated with comedonecrosis can produce extensive pleomorphic or granular calcific deposits in ductal branches (9,16). Bilateral cancers are rare, occurring in 175 (4.3%) of 4,087 breast cancer cases in one series (17). Synchronous cancers occur in 15.2%–39.5% of patients with bilateral cancer (18–20), with a higher prevalence of synchronous cancers detected in more recent series (44% and 52%) probably due to advances in screen-film mammography (17,21). In our patient, the calcifications were neither pleomorphic nor granular (suggesting that bilateral cancer was less likely), but a biopsy was prompted by their new development and her family history of breast cancer.
Although breast cancer in pregnant women may appear as pleomorphic microcalcifications (2), to our knowledge the appearance of bilateral regional microcalcifications in a recently lactating woman has not previously been reported. The usual mammographic finding in a pregnant or lactating woman is that of generalized density due to glandular proliferation (2), although some authors dispute this (22). Dense mammographic changes may persist for months after the cessation of breast feeding and subsequently return to a less dense pattern. Breast cancer can be depicted at mammography in young women or in pregnant or lactating women as pleomorphic calcifications or spiculated masses (2,23); thus, mammograms should be obtained in pregnant or lactating women suspected of having breast lumps to prevent a missed cancer diagnosis (2).
Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or within 1 year thereafter (1). It is the most frequently diagnosed cancer during pregnancy and lactation, with an incidence of one in 3,000 to one in 10,000 patients. However, since this incidence of breast cancer is no greater than that of other women of childbearing age, the association between pregnancy and breast cancer may therefore be more coincidental than causal (1). Our patient was first suspected of having cancer after a mammogram was obtained after pregnancy, which was an unusual circumstance for a young woman. There is a paucity of imaging literature on asymptomatic lactating women, since it is unusual for these women, who are usually young, to undergo mammography. However, mammographic examination may become more common in older lactating women with the advent of in vitro fertilization and other methods to overcome infertility. These technologies have extended women’s childbearing years into ages in which breast cancer is more common (24,25) and in which mammographic examination would be advocated (26). Radiologists should be aware that the mammographic and MR imaging findings in our recently lactating patient may represent benign disease. However, until other cases are reported and have documented follow-up, a biopsy may still be appropriate.
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FOOTNOTES
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Author contributions: Guarantor of integrity of entire study, D.T.S., D.M.I.; study concepts and design, D.T.S., D.M.I.; definition of intellectual; content, all authors; literature research, all authors; clinical studies, all authors; data acquisition and analysis, all authors; manuscript preparation, editing, and review, all authors.
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ABSTRACT
INTRODUCTION
