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Calcification

The two main types of breast calcification are calcium phosphate and calcium oxalate (wedellite). Calcium phosphate is the type of calcium most commonly encountered in the breast and is relatively easy to see on routine staining, presenting as bluish crystalline foci. It is seen in both benign and malignant lesions. Calcium oxalate, on the other hand is more difficult to see on routine H+E staining. It is visible as refractile crystals under polarised light, usually within benign cysts or dilated ducts.

One of the targets of the mammographic screening program is pre-invasive breast cancer (DCIS). Microcalcification is seen in breast carcinomas in 30-75% of cases. Approximately 90% of DCIS calcification clusters have more than 10 flecks of calcium. The most common features of calcifications due to DCIS are granular calcifications with irregularity in density, shape, size and cluster. These features are present in >90% of cases of DCIS but they are also commonly found in benign causes of calcification. The more specific features of DCIS include a ductal distribution and rod-like branching shapes. Punctate (round or oval) calcifications are also commonly found in DCIS.

The pattern of calcification varies with the grade of the DCIS. The majority of cases of DCIS detected by mammographic screening in the UK is of high nuclear grade (87%). High grade DCIS with comedonecrosis is associated histologically with relatively large central foci of calcification, associated with central necrotic debris. The mammographic correlate is linear or rod-shaped calcification or calcification with a ductal distribution.

DCIS grows twice as fast in the nipple plane. A triangular distribution, aimed in the general direction of the nipple may also be seen. Occasionally high grade DCIS can be very extensive, involving many duct branches, but still has a characteristic segmental distribution.

Low grade DCIS, which we encountered in the page describing epithelial proliferation, commonly has a cribriform architecture. Histologically, the calcium is present as small punctate foci in the secondary lumina. The mammographic correlate is granular or punctate calcification. Diffusely scattered calcifications are generally benign.

Please remember that microscopy commonly reveals calcification that is not apparent by mammography. It is vital therefore that when assessing core biopsies, you correlate the type of calcification visualised with the microscope, with the target calcium seen on mammography. Often, the radiologist will have x-rayed the cores to confirm that the target calcium has been biopsied. Screening core biopsies should always be reviewed at a multidisciplinary meeting, comprising at least a pathologist and radiologist, to ensure that the biopsy is representative of the mammographic abnormality.

Occasionally, the radiologist will confirm that calcium was present in the core biopsy x-ray but microscopy fails to reveal the calcium. In this case, the following procedure is recommended:

  1. Polarise the sections to exclude the presence of calcium oxalate.
  2. Examine deeper levels.
  3. If no calcium is seen on deeper levels, x-ray the paraffin blocks to ensure that the calcium has not dissolved (this has been documented to occur in formalin after about 3 days suspension).
  4. If calcium is visualised on the block x-ray, examine deeper levels, if necessary to extinction of the block.
  5. Occasionally calcium may be lost during microtomy. There is not alot that can be done in this instance, except to carefully examine the surrounding non-calcified tissue and then discuss the findings at the multi-disciplinary meeting.