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Metallic Punctate Densities in the Breast after Chinese Herbal Treatment: Mammographic Findings¹

¹ From the Departments of Radiology (W.K.M., J.G.I., K.M.Y., M.C.H.) and Surgery (D.Y.N.), Seoul National University Hospital and the Institute of Radiation Medicine, Seoul National University Medical Research Center, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Korea, and the Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (J.M.P.). Received February 19, 1999; revision requested April 5; revision received May 12; accepted June 28. W.K.M. supported by grant 01-99-047 from the Seoul National University Hospital Research Fund. Address reprint requests to W.K.M. (e-mail: moonwk@radcom.snu.ac.kr).

	Abstract

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To describe the mammographic features of metallic punctate densities seen in women who were treated with the herb go-yak for breast abscess and to explain the cause of these findings.

MATERIALS AND METHODS: Mammograms showing metallic punctate densities that appeared to be microcalcifications in 34 women were analyzed retrospectively with attention to the location, shape, distribution, and depth of the lesions. In all patients, go-yak was applied into the open wound after abscess drainage 6–42 years before mammography. In six patients, histopathologic specimens were obtained after needle localization.

RESULTS: Metallic densities were in the subareolar or central breast in 24 (71%) of 34 patients. The shape was predominantly round or punctate in all patients, but rod-shaped or linear lesions were found in seven patients. The distribution and depth of lesions were variable, but they extended to the subcutaneous fat in 29 patients (85%). A high concentration of lead was found in the histopathologic specimens and herb samples.

CONCLUSION: Lead deposits associated with go-yak treatment should be included in the differential diagnosis when the suspected microcalcifications are of unusually high density, are central in location, and extend into the subcutaneous fat in Asian women with a history of breast abscess.

Index terms: Breast, abnormalities, 00.811 • Breast, abscess, 00.212 • Breast, calcification, 00.811 • Breast, diseases, 00.212 • Breast neoplasms, diagnosis, 00.3113 • Breast radiography, 00.112, 00.113, 00.114, 00.115 • Foreign bodies, 00.46 • Lead

	Introduction

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Calcium-like artifacts on mammograms are mostly due to defective film processing or foreign bodies in or on the skin. Particles of dirt on the cassette or the intensifying screen and some powders or ointments on the skin can simulate microcalcifications (1–3), but such artifacts are rarely localized to the breast parenchyma on a second mammogram. Breast foreign bodies related to medical procedures or treatment include sewing needles, calcific suture materials, catheter cuffs, intranodal gold deposits, and fragments of localizing wires or core biopsy needles (4–10). These particles occasionally are small enough to mimic microcalcifications, but careful attention to their high radiographic density and clinical histories would prevent unnecessary biopsy.

A topical Chinese herbal medicine called "go-yak" was widely used before the 1970s as a folk remedy for women with breast inflammation and abscess in Korea (11). In women who had a history of breast abscess, we observed metallic punctate densities mimicking microcalcifications, which, to our knowledge, have not been documented in the literature. The similarities in clinical and therapeutic histories of the patients suggested that these metallic punctate densities might be from go-yak. With increasing use of screening mammography in Asian countries (12), these unusual metallic punctate densities are of interest to avoid unnecessary biopsy.

The purpose of this study was to describe the mammographic features of metallic punctate densities seen in women who were treated with go-yak for breast abscess and to explain the cause of these findings.

	MATERIALS AND METHODS

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A search of our mammography teaching files identified 37 women with a history of go-yak treatment for breast abscess between March 1994 and March 1997. During this period, about 15,500 women underwent mammography in our institutions. After mammographic, clinical, and histopathologic review of cases, three patients were excluded because only benign secretory calcifications were seen in two patients and breast malignancy was associated in one patient. Thirty-four patients (age range, 37–73 years; mean, 59 years) with mammograms showing metallic punctate densities that appeared to be microcalcifications form the study population. They were all Korean.

A history of go-yak treatment for breast abscess was obtained by means of a clinical history questionnaire at the time of mammography and was confirmed by the patient at a second visit (n = 27) or by means of telephone interview (n = 7). All women were treated in similar ways and with the same herb 6–42 years (mean, 27 years) before mammography. Go-yak was repeatedly applied or inserted into the open wound after abscess drainage. The duration of the herbal treatment was 3–13 weeks (mean, 7 weeks). No patient had a history of trauma or an episode that could cause known foreign bodies in the breast (3,4). No patient had a history of extensive breast surgery such as reduction or augmentation mammoplasty, radiation therapy to the breast, or needle biopsy. Two patients had a history of surgical biopsy for benign lesions.

Thirty patients were asymptomatic, and four patients had mild discomfort in the treated breast. At physical examination, one to three cutaneous scars were found in 26 patients. No patient had a palpable breast mass or tattoos on the skin. In six patients, a wire-guided surgical biopsy was performed because the metallic punctate densities were interpreted as indeterminate calcifications. Thirty of 34 patients were followed up, and no evidence of malignancy was seen in any patient during follow-up of 3–47 months (mean, 12 months).

Mammography was performed by using a conventional screen-film technique and dedicated equipment (Senographe 600T; GE Medical Systems, Milwaukee, Wis), single-emulsion film, and dedicated processing equipment. Routine mediolateral oblique and craniocaudal mammograms were available in all patients. Diagnostic mammograms were obtained in 27 patients with the addition of one or two of the following examinations: spot-compression magnifications (n = 15), tangential views (n = 11), and mammograms with radiopaque markers on the scar (n = 13). Specimen radiographs were obtained after biopsy in the six patients in whom biopsy was performed. Follow-up mammograms with intervals of 3–36 months were available in 20 patients. In 19 of those 20 patients, follow-up mammograms were obtained without any surgical interventions.

All mammograms were retrospectively analyzed by two radiologists (W.K.M., J.M.P.) independently, and decisions on the findings were reached by consensus. Particular attention was given to the location, shape, size, number, distribution, and depth of the metallic punctate densities. In addition to the metallic punctate densities, the breast composition, associated calcifications or masses, and findings such as skin thickening, nipple retraction, architectural distortion, and axillary adenopathy were also evaluated. The characterization of the lesions was performed according to the American College of Radiology Breast Imaging Reporting and Data System (13).

For evaluation of lesion density, 34 consecutive mammograms of microcalcifications proved to be malignant were mixed with those of metallic punctate densities, and two radiologists (J.G.I., K.M.Y.) were asked to detect metallic densities by visual inspection. They evaluated the images independently, and the disagreements were resolved by consensus.

With use of a digital densitometer (Densitometer Number 301; X-Rite, Grandville, Mich), the corrected lesion density was calculated as the density of breast parenchyma minus lesion density divided by the density of breast parenchyma. Because the smallest diameter that could be measured with the densitometer was 1 mm and lesion size was sometimes smaller than 1 mm, lesion density was corrected by using the density of the surrounding breast parenchyma.

The Wilcoxon rank sum test was used to assess the statistical significance of differences in the corrected density between metallic densities and malignant microcalcifications. A P value less than .05 was considered to indicate a statistically significant difference.

Specimen radiographs were reviewed to confirm that the metallic punctate densities had been excised. When mammographically detected metallic punctate densities were not found in the histopathologic specimen, further radiographs of the paraffin blocks were obtained. The histopathologic slides were stained with hematoxylin-eosin and safranin O stains, and they were reviewed by an experienced pathologist using conventional microscopy. Particular attention was given to the histopathologic characteristics of metallic densities, the presence of foreign body reactions, and association with true calcifications or atypical cells.

To explain the cause of these metallic punctate densities, the histopathologic specimen and the herb sample were analyzed by means of atomic absorption spectrometry (SpectrAA 800; Varian, Melbourne, Australia). Paraffin blocks containing more than 100 metallic densities on specimen mammograms were selected for this analysis, and surgical specimens from two patients met this criterion. The herb samples (Lee Myung-rae Go-Yak; Myung-rae Pharmacy, Seoul, Korea) probably used for treatment of breast abscess in the patients in our study were collected from a dispensary of Chinese medicine.

The analysis was focused to see if herb samples contained metals such as zinc, iron, aluminum, lead, and mercury that are reported as possible contaminants in ointments or Chinese herbal medicines (4,14). The exact content and mechanism of action of go-yak were not as well described as those of other Chinese herbal medicines.

	RESULTS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Breast composition at mammography was fatty in 21 patients, scattered fibroglandular in eight, and heterogeneously or extremely dense in five patients.

The metallic densities were in the subareolar (n = 11) or central (n = 13) breast in 24 patients (71%) (Fig 1), the upper-outer or upper-inner breast in six patients (18%), the lower-outer or lower-inner breast in three patients (9%), and the axilla in one patient (3%). The shape of the lesions was predominantly round or punctate in all patients, but rod-shaped or linear lesions were found in seven patients. The average size of the lesions was less than 0.5 mm in 30 patients and 0.5–1.0 mm in four patients. The number of lesions was five to 10 in five patients, 10–50 in 15 patients, and more than 50 in 14 patients.

View larger version (83K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. (a) Spot-compression magnification mammogram obtained in a craniocaudal projection in a 36-year-old woman shows clusters of metallic densities in the subcutaneous (arrow) and anterior portions of the breast. Although the size of each particle is variable, the shape is predominantly round or punctate. (b) Mediolateral oblique mammogram with metallic markers at the cutaneous scar shows metallic punctate densities (arrows) in the area corresponding to the incision site for abscess drainage.

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. (a) Spot-compression magnification mammogram obtained in a craniocaudal projection in a 36-year-old woman shows clusters of metallic densities in the subcutaneous (arrow) and anterior portions of the breast. Although the size of each particle is variable, the shape is predominantly round or punctate. (b) Mediolateral oblique mammogram with metallic markers at the cutaneous scar shows metallic punctate densities (arrows) in the area corresponding to the incision site for abscess drainage.

View larger version (165K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. (a) Mediolateral oblique and (b) craniocaudal mammograms obtained in a 60-year-old woman show metallic punctate densities (arrows) that appear to be microcalcifications in the upper-outer quadrant of the breast. These metallic punctate densities were interpreted as indeterminate calcifications owing to their clustering, pleomorphism, and segmental distribution. (c) Radiograph of the specimen shows clustered metallic particles (arrow). The morphology and density of the particles are heterogeneous. (d) Photomicrograph shows three foci of foreign bodies (arrows) surrounded by giant cells (arrowhead) in the stroma of the breast. (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (158K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. (a) Mediolateral oblique and (b) craniocaudal mammograms obtained in a 60-year-old woman show metallic punctate densities (arrows) that appear to be microcalcifications in the upper-outer quadrant of the breast. These metallic punctate densities were interpreted as indeterminate calcifications owing to their clustering, pleomorphism, and segmental distribution. (c) Radiograph of the specimen shows clustered metallic particles (arrow). The morphology and density of the particles are heterogeneous. (d) Photomicrograph shows three foci of foreign bodies (arrows) surrounded by giant cells (arrowhead) in the stroma of the breast. (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. (a) Mediolateral oblique and (b) craniocaudal mammograms obtained in a 60-year-old woman show metallic punctate densities (arrows) that appear to be microcalcifications in the upper-outer quadrant of the breast. These metallic punctate densities were interpreted as indeterminate calcifications owing to their clustering, pleomorphism, and segmental distribution. (c) Radiograph of the specimen shows clustered metallic particles (arrow). The morphology and density of the particles are heterogeneous. (d) Photomicrograph shows three foci of foreign bodies (arrows) surrounded by giant cells (arrowhead) in the stroma of the breast. (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (100K): [in this window] [in a new window] [Download PPT slide]   Figure 2d. (a) Mediolateral oblique and (b) craniocaudal mammograms obtained in a 60-year-old woman show metallic punctate densities (arrows) that appear to be microcalcifications in the upper-outer quadrant of the breast. These metallic punctate densities were interpreted as indeterminate calcifications owing to their clustering, pleomorphism, and segmental distribution. (c) Radiograph of the specimen shows clustered metallic particles (arrow). The morphology and density of the particles are heterogeneous. (d) Photomicrograph shows three foci of foreign bodies (arrows) surrounded by giant cells (arrowhead) in the stroma of the breast. (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (162K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Spot-compression magnification mammogram obtained in a craniocaudal projection in a 58-year-old woman shows clustered metallic punctate densities forming a "calcific" mass (arrow) in the central portion of the breast. Note the focal thickening and retraction of the skin (arrowhead) secondary to the incision for abscess drainage.

On mammograms obtained in tangential views in 11 patients, metallic punctate densities were predominantly in the skin—in the subcutaneous fat in seven patients and in the parenchyma of the breast in four patients. On the mammograms obtained in the 13 patients with radiopaque markers at the cutaneous scar, the metallic punctate densities were seen in the area corresponding to the incision site in all 13 patients (Fig 1).

Skin thickening or nipple retraction and associated architectural distortion were seen in 21 patients (62%) (Fig 3). Fat necrosis or secretory calcifications were seen near the metallic punctate densities in 13 patients (38%). In three patients, a well-defined nodule proved to be a fibroadenoma at core biopsy was seen in one of the other quadrants of the breast. No patient had associated axillary adenopathy. The number and distribution of metallic punctate densities did not change on follow-up mammograms obtained 3–36 months later in all 19 patients in whom follow-up mammograms were obtained without intervention.

At visual inspection, punctate densities were regarded as metallic in 25 (74%) of 34 patients, whereas none of the malignant calcifications was regarded as metallic. Corrected lesion density, calculated as the density of breast parenchyma minus lesion density divided by the density of breast parenchyma, was 0.15–0.89 (mean, 0.59) for the metallic punctate densities and 0.02–0.46 (mean, 0.17) for the malignant microcalcifications. The difference was statistically significant (P < .01).

At specimen mammography, metallic punctate densities were seen in five of six patients. The localizing wire was seen within 5 mm of the lesions in all five patients. In one patient, the biopsy failed, and metallic punctate densities remained in the skin on follow-up mammograms obtained 3 months after surgery.

At histopathologic examination, clustered particles surrounded by a few giant cells were found in the stroma in all five patients (Fig 2d). The metallic particles varied in diameter (range, 0.1–1.2 mm; mean, 0.4 mm ± 0.3 [SD]). They were typically brownish black with hematoxylin-eosin staining. In the remaining breast, only mild fibrocystic change was seen in the otherwise normal breast tissue. True microcalcifications or atypical cells were not found in any patients.

Atomic absorption spectrometric analysis showed positive results only for the presence of lead. In the histopathologic specimen, lead concentration was 2,800 and 4,700 µg/mg in two patients. In the herb sample, lead concentration was 20.1% of the sample mass. The amount of other metals such as zinc, iron, aluminum, and mercury was negligible in both the histopathologic specimen and the herb sample. Blood lead levels were not checked, because no patient had a history or the present signs and symptoms of lead poisoning.

	DISCUSSION

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
In women who had a history of breast abscess, we observed unusual metallic punctate densities that mimicked microcalcifications on mammograms. A causal relationship between the metallic punctate densities and topical herbal treatment for breast abscess was speculated because all of these patients had a similar clinical history and the lesions were always found near the incision site. Histopathologic examination of surgical specimens showed the clustered particles surrounded by a few giant cells in the stroma, and atomic absorption spectrometric analysis revealed high concentrations of lead in both the histopathologic specimens and the herb samples. Metallic punctate densities on mammograms in the patients in our study were probably due to contamination by lead contained in go-yak incorporated into the breast as the herb was repeatedly applied or inserted into the open wound after abscess drainage.

Side effects of herbal medicine are not rare (15,16), and lead or mercury poisoning following ingestion of Chinese or Indian herbal medicine has been reported in Asian and Western countries (17–19). Because of the lack of quality control, any herbal medication can be contaminated with undeclared prescription drugs or unacceptable materials such as methyltestosterone, dexamethasone, prednisone, indomethacin, diazepam, caffeine, ethaverine hydrochloride, gold, zinc, mercury, or lead (14–21), as in our study. Our results show that lead deposits in the breast remain inert for a long time without a change in the number and distribution.

In most cases, the distinction between metallic punctate densities associated with go-yak treatment and malignant microcalcifications was easy for the experienced radiologists because the metallic punctate densities had a typical location, shape, distribution, and density on mammograms. In six cases (18%), however, the metallic punctate densities did not have typical mammographic features, and they were interpreted as indeterminate calcifications, which led to excisional biopsy after wire-guided surgical biopsy. They were deep-seated, linear, or segmental (Fig 2) in distribution, and of a density similar to that of true calcifications. The difference in mammographic features among cases may result from variabilities in herbal treatment and abscess drainage.

For the evaluation of lesion density, we used a densitometric measurement with 1-mm diameter and a correction with use of the density of surrounding breast parenchyma. The measurement, however, might be more accurate if microdensitometers are available.

In conclusion, lead deposits associated with go-yak treatment should be included in the differential diagnosis when suspected calcifications are of unusually high density, are central in location, and extend into the subcutaneous fat in Asian women with a history of breast abscess. These metallic punctate densities on mammograms are probably due to lead contained in go-yak incorporated into the breast.

	Footnotes

 
Author contributions: Guarantor of integrity of entire study, W.K.M.; study concepts and design, W.K.M., J.M.P., D.Y.N.; definition of intellectual content, W.K.M., J.M.P., J.G.I.; literature research, W.K.M., J.M.P., J.G.I.; clinical studies, W.K.M., J.M.P., D.Y.N., J.G.I.; data acquisition, W.K.M., J.M.P.; data analysis, W.K.M., J.M.P., J.G.I., K.M.Y.; statistical analysis, W.K.M., J.M.P.; manuscript preparation, editing, and review, W.K.M., K.M.Y., M.C.H.

	References

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 

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