Multiple Clusters of Crushed Stone-like Calcifications on the Mammogram Produced by Malignant Processes

Chapter 3
Multiple Clusters of Crushed Stone-like Calcifications on the Mammogram Produced by Malignant Processes

Mammograms showing multiple clusters (or rarely a single cluster) of crushed stone-like calcifications that represent only a portion of the underlying disease can be subdivided by careful correlation of mammographic; large-section histological; and subgross, thick-section histological images into the following two subgroups. Group 2A The in situ process is primarily confined to TDLUs that are separated from each other by normal tissue, although histology may reveal a few involved ducts. In these cases there is reasonable concordance between the mammographic and histological findings. The crushed stone-like calcifications may also be associated with powdery calcifications, seen in close proximity on the mammograms, representing Grade 2 and Grade 1 in situ carcinoma side by side. Group 2B Although the mammographic image may show multiple clusters which appear similar to those in Group 2A, large-section histological examination demonstrates tightly packed cancerous TDLUs and ducts covering a larger area than that indicated by the calcifications detected at mammography. MRI of the breast plays an important role in revealing the true extent and confluent nature of the underlying disease. In some extreme cases very large numbers of clusters of crushed stone-like calcifications are visible on the mammogram, often associated with some casting type calcifications. The larger the number of clusters, the more difficult it is to discern the individual clusters. Correlation with large-section and subgross, 3D histology shows a high density of tightly packed cancerous TDLUs and ducts with little, if any, normal tissue in between. Histological signs of neoductgenesis and lymph vessel invasion are often present and may account for the occasional poor outcome.

Group 2A: Multiple Foci on Histology with Intervening Normal Tissue

Example 3.1

A 62-year-old asymptomatic woman, screening examination.

Ex. 3.1-1 & 2 Details of the left MLO(1) and CC (2) screening mammograms. There are several clusters of microcalcifications in the lower-outer quadrant.

Ex. 3.1-3 Microfocus magnification, left CC projection. There is normal breast tissue separating the clusters of calcifications from each other. The first step in calcification analysis is to determine their distribution. When they are clustered and the individual calcifications are discernible, the probability of malignancy increases with an increasing number of clusters. The second step is to evaluate the shape and density of the individual calcifications. The greater their variation in shape and density, the higher the probability that they are malignant type calcifications.

Ex. 3.1-4 Subgross 3D histology confirms that the malignant type calcifications arise within the TDLUs which are distended by the cancer cells. The terminal ducts do not contain malignant cells. Although the current terminology is “DCIS,” in reality the disease process is confined to the lobules and does not appear in the ducts in this case. A more precise term would be Grade 2 in situ carcinoma confined to several lobules.

Ex. 3.1-5 to 10 Stereoscopic image pairs of subgross, 3D histology showing several TDLUs distended by in situ carcinoma. The individual acini are larger than normal-sized TDLUs.

Ex. 3.1-11 & 12 This stereoscopic image pair demonstrates that the distended TDLU containing the malignant type calcifications measures 4 mm. Stereotactic technique is required for accurate preoperative percutaneous biopsy.

Treatment and outcome: Sector resection and postoperative irradiation. The patient died of acute leukemia 12 years after treatment. During the follow-up period there was no evidence of breast cancer recurrence.

Ex. 3.1-13 & 14 Histological diagnosis: Grade 2 in situ carcinoma with a cribriform pattern, central necrosis, and amorphous calcifications.

Example 3.2

A 55-year-old asymptomatic woman, screening examination. She was called back for further assessment of the calcifications detected on the screening mammograms.

Ex. 3.2-1 Microfocus magnification mammography of the right breast, CC projection. Multiple clusters of crushed stone-like calcifications are seen without an associated tumor mass. The calcifications vary in size and density, and some are triangular, arrowhead-shaped, and mammographically malignant.

Ex. 3.2-2 Subgross,thick-section histology.The TDLUs distended by in situ carcinoma and containing the crushed stone-like calcifications are encircled. Foci of in situ carcinoma not containing calcifications, and thus occult to mammography, are seen within the rectangles.

Ex. 3.2-3 to 8 Progressively enlarged stereoscopic views of this subgross, 3D specimen. These images demonstrate that the multiple clusters of calcifications are restricted to the distended TDLUs, but also show noncalcified malignant foci nearby.

Ex. 3.2-9 to 11 Stereoscopic image pair (9 & 10) and medium-power conventional histological image (11) of a single cancerous TDLU, with the terminal duct also involved.

Final histology: Grade 2 in situ carcinoma over an area measuring 50 mm in diameter. Cancer cells were demonstrated at the resection margin.

Treatment and outcome: Sector resection. Histological examination has found cancer foci on the margin. Mastectomy: no residual tumor, pNX. The patient was symptom-free at the most recent follow-up examination 12 years after operation.

Ex. 3.2-12 to 15 The gap between the mammogram with its lower resolution and conventional histology with its exquisite higher resolution can be bridged by sub-gross, thick-section histology for better mammographic-histological correlation, as illustrated in this step wedge.

Comment

The multiple clusters on the mammogram reflect the multiple cancerous TDLUs. Unlike the contiguous tumor growth characteristic of casting type calcification cases and the subgroup 2B, the multiple cluster crushed stone-like calcification cases described at the beginning of this chapter originate in individual TDLUs that are separated from each other by a few millimeters of intervening normal tissue. Viewing the large thick-section/3D histological slices not only provides excellent correlation with the mammographic findings but also unearths additional, valuable information, such as mammographically occult cancer foci. In this particular example, the distance between two of the calcified TDLUs was 8 mm. These observations suggest that the term “close” surgical margin may be an unreliable description when the finding on the mammogram consists of multiple clusters of crushed stone-like calcifications.

Example 3.3

This 65-year-old woman was called back from mammography screening for assessment of multiple clusters of calcifications in the right breast.

Ex. 3.3-1 to 3 Right breast, MLO projection. Contact (1) and microfocus magnification (2, 3) images. Many clusters of crushed stone-like calcifications are scattered throughout much of the breast.

Ex. 3.3-4 to 6 Right breast CC projection (4). The microfocus magnification images (5 & 6) reveal the diversity of the individual calcifications within the clusters.

Ex. 3.3-7 to 9 Right breast, CC projection, microfocus magnification images at increasing enlargement.

Ex. 3.3-10 to 13 Radiographs of the preoperative vacuum-assisted biopsy specimen.

Ex. 3.3-14 & 15 Histologic image of the vacuum-assisted biopsy specimen (H & E): in situ carcinoma.

Ex. 3.3-16 Radiograph of one of the operative specimen slices.

Ex. 3.3-17 & 18 Subgross, thick-section (3D) histological image pair of this multifocal in situ carcinoma.

Ex. 3.3-19 Magnification of the left half of the specimen radiograph in Ex. 3.3-16.

Ex. 3.3-20 Magnification of the remaining half of the specimen radiograph in Ex. 3.3-16.

Ex. 3.3-21 Large-section histology image shows the extensive multifocal in situ carcinoma involving individual, separate TDLUs.

Ex. 3.3-22 to 26 Histological-mammographic correlation of the multiple clusters of cancerous TDLUs containing the crushed ston-elike calcifications

Ex. 3.3-27 to 29 The histological image shows a single TDLU distended by in situ carcinoma, central necrosis and amorphous calcifications. This corresponds to one of the many clusters of crushed stone-like calcifications on the mammogram.

Ex. 3.3-30 & 31 The in situ carcinoma distending several TDLUs and a duct is demonstrated in comparative subgross, thick-section (3D) (30) and low-power conventional (31) histological sections.

Ex. 3.3-32 & 33 Specimen radiographs of multiple clusters of crushed stone-like, pleomorphic calcifications.

Ex. 3.3-34 & 35 Subgross, thick-section (3D) histological image of one of the TDLUs distended by Grade 2 in situ carcinoma, containing the crushed stone-like calcifications.

Ex. 3.3-36 The Grade 2 in situ carcinoma is associated with the amorphous calcifications. These are seen on the mammogram as crushed stone-like, pleomorphic calcifications.

Ex. 3.3-37 & 38 Subgross, thick-section (3D) image pair of several cancerous TDLUs and ducts.

Ex. 3.3-39 Radiograph of a specimen slice showing the crushed stone-like calcifications (rectangle) and the powdery calcifications (circles). Compare with the corresponding subgross (37 & 38) and conventional (40) histological images.

Ex. 3.3-40 Mammographic–histological correlation (39 & 40) of adjacent TDLUs containing Grade 2 and Grade 1 in situ carcinoma. The Grade 2 in situ process (rectangle) distends the TDLU to a greater extent and contains the crushed stone–like calcifications, while the Grade 1 in situ carcinoma distends the TDLU considerably less and contains the powdery calcifications, if there is any calcification at all associated with it.

Ex. 3.3-41 & 42 Subgross histological image pair of several TDLUs and a subsegmental duct distended by in situ carcinoma.

Ex. 3.3-43 & 44 Specimen radiographs containing crushed stone-like (43) and multiple clusters of powdery (44) calcifications.

Ex. 3.3-45 & 46 Stereotactic image pair showing acini greatly distended by Grade 2 in situ carcinoma and intraluminal amorphous calcifications (oval) and less distended acini containing Grade 1 in situ cancer, interconnected by cancerous ducts.

Ex. 3.3-47 to 48 Subgross, thick-section (3D) and large-section histological images of several adjacent TDLUs. The cystically dilated TDLU (rectangle) contains psammoma body-like calcifications that are shown on the mammogram as powdery and teacup-like microcalcifications. Also the Grade 1 in situ carcinoma (circles) contain powdery calcifications, mammographically indistinguishable from those seen in cystically dilated TDLUs or in sclerosing adenosis.

Ex. 3.3-49 Specimen radiograph demonstrating powdery and teacup-like calcifications in benign fibrocystic change.

Ex. 3.3-50 Low-power histological image of cystically dilated acini lined with apocrine metaplasia. The summation of the psammoma body-like calcifications can be seen on the mammogram as either powdery or teacup-like calcifications.

Example 3.4

A 54-year-old asymptomatic woman, screening examination. Her sister had breast cancer at age 59 years.

Ex. 3.4-1 & 2 Screening mammograms, right breast, MLO (1) and CC (2) projections. There is a single cluster of crushed stone-like calcifications in the lower-inner quadrant.

Ex. 3.4-3 Microfocus magnification: the calcifications are closely spaced, irregularly shaped and vary in size and density These microcalcifications are of a mammographically malignant type.

Ex. 3.4-4 & 5 Specimen radiograph (4) and low-power histological image of the vacuum-assisted biopsy specimen (5). Histology: in situ carcinoma.

Ex. 3.4-6 Higher-power histological image of this Grade 2 in situ carcinoma.

Ex. 3.4-7 Operative specimen radiograph. The remaining calcifications have been removed with good margins.

Ex. 3.4-8 & 9 Histological findings: 15 mm ⊠ 8 mm Grade 2 in situ carcinoma associated with central necrosis and amorphous calcifications. There were no signs of invasion. A post-biopsy scar and an amorphous calcification (displaced) are seen within the oval. Histologically tumor-free margin: 8 mm. The patient declined postoperative radiotherapy.

Four years later, at routine follow-up mammography, two new clusters of crushed stone-like calcifications were detected at the site of operation. The patient was still asymptomatic.

Ex. 3.4-10 & 11 Right breast, microfocus magnification images in the MLO (9) and CC (10) projections. The newly developed clusters of crushed stone-like calcifications resemble the calcifications previously removed from this site. There is no associated tumor mass.

Ex. 3.4-12 Right breast, microfocus magnification image in the lateromedial horizontal projection.

Ex. 3.4-13 Vacuum-assisted biopsy specimen radiograph.

Ex. 3.4-14 & 15 Low- and intermediate-power histological images of the biopsy specimen: in situ carcinoma with necrosis and amorphous calcification.

Ex. 3.4-16 Operative specimen radiograph following preoperative localization using the bracketing technique.

Ex. 3.4-17 Large-section histology. The TDLUs containing the in situ carcinoma are within the rectangle.

Ex. 3.4-18 Operative specimen radiograph using microfocus magnification technique. Due to the increased image resolution, additional calcifications can now be visualized, suggesting the presence of more extensive disease.

Ex. 3.4-19 Sliced specimen radiograph.

Ex. 3.4-20 Paraffin block radiograph showing the multiple clusters of calcifications.

Ex. 3.4-21 Low-power histological image. Numerous acini are filled with malignant cells, but only few of them contain calcifications.

Ex. 3.4-22 An additional focus of calcified and noncalcified in situ carcinoma.

Ex. 3.4-23 Medium-power histological image.

Ex. 3.4-24 to 26 Mammographic-histological correlation of this in situ carcinoma.

Treatment and outcome: Sector resection and postoperative irradiation following the diagnosis of recurrence. The patient had no evidence of disease at the most recent follow-up examination 2 years after her second operation.

Example 3.5

A 57-year-old asymptomatic woman, screening examination.

Ex. 3.5-1 & 2 Right breast, MLO (1) and CC projections (2). The “elbow sign” on the MLO projection and the “tent sign” on the CC projection indicate the presence of a pathological abnormality in the upper-outer quadrant of the breast.

Ex. 3.5-3 Microfocus magnification combined with spot compression reveals a spiculated (stellate) lesion without associated calcifications. Mammographically malignant tumor.

Ex. 3.5-4 Specimen radiograph of the surgically removed tumor.

Follow-up examination 6 years after surgery.

Ex. 3.5-5 & 6 Right and left breasts, detailed views in the MLO projection. Postsurgical scar with calcified oil cysts are seen in the right breast (5). A few clusters of de-novo crushed stone-like calcifications have developed in the lateral portion of the left breast (6).

Ex. 3.5-7 Microfocus magnification of the de-novo calcification clusters: the individual particles are in close proximity to each other, vary in density, size and shape, and are mammographically of the malignant type.

Ex. 3.5-8 Left breast, CC projection, showing the cluster of calcifications.

Ex. 3.5-9 Microfocus magnification demonstrates that there are multiple clusters of calcifications.

Ex. 3.5-10 Microfocus magnification in the lateromedial horizontal projection.

Ex. 3.5-11 to 14 Vacuum-assisted specimen radiographs without (11) and with (12) calcifications. Histological examination reveals in situ carcinoma in the noncalcified sample as well (13, 14).

Ex. 3.5-15 to 17 Vacuum-assisted specimen radiograph without calcifications correlated with histology. The preoperative biopsy establishes the diagnosis of in situ carcinoma.

Ex. 3.5-18 & 19 Radiographs of the operative specimen slices.

Ex. 3.5-20 In this specimen slice there appears to be a spiculated lesion (encircled) adjacent to the malignant type calcifications.

Ex. 3.5-21 The large-section histological image can be correlated with the specimen radiograph. The area containing in situ carcinoma foci and the spiculated lesion has been outlined by the pathologist.

Ex. 3.5-22 The large-section histology image can be compared with the detailed photomicrographs on these two pages (Ex. 3.5-23 to 29).

Ex. 3.5-23 The star-shaped lesion (encircled on Ex. 3.5-22) is a scar caused by the preoperative needle biopsy performed 3 weeks earlier. There are in situ carcinoma foci (ovals) entrapped within the scar. Another in situ focus is outlined by a rectangle.

The photomicrographs on this page are higher-power views of the in situ foci within the rectangle on Ex. 3.5-22.

Ex. 3.5-24 High-power magnification of one of the in situ foci (upper oval on Ex. 3.5-23) with solid cell proliferation, central necrosis, and amorphous calcification.

Ex. 3.5-25 Higher magnification of another focus of in situ carcinoma, seen on Ex. 3.5-23 within the rectangle.

Ex. 3.5-26 to 29 Four enlarged images of the noncalcified in situ carcinoma foci within the rectangle on Ex. 3.5-22. The area with in situ carcinoma measured 40 mm ⊠ 15 mm, considerably larger than the area with crushed stone-like calcifications on the mammogram.

Treatment and outcome: Right breast: sector resection and postoperative irradiation. Left breast (6 years later): mastectomy. The patient had no signs of recurrence 2 years following mastectomy of the left breast.

Example 3.6

A 47-year-old asymptomatic woman, screening examination. She was called back for further assessment of the small cluster of calcifications detected on the screening mammograms.

Ex. 3.6-1 to 3 Right breast, MLO projection and microfocus magnification views of the cluster of calcifications. These crushed stonelike calcifications are closely spaced and vary in size, shape, and density. Some of them resemble broken needle tips. The cluster is composed of mammographically malignant type calcifications.