Advanced pathology techniques challenge notions about breast cancer

March 5, 2008

Cutting-edge pathology techniques will demonstrate the true nature of breast cancer during the opening session of a categorical course Friday afternoon. Rare and potentially revolutionary, the new methods look set to challenge radiologists’ understanding of breast cancer and could alter their approach to imaging interpretation.

Cutting-edge pathology techniques will demonstrate the true nature of breast cancer during the opening session of a categorical course Friday afternoon. Rare and potentially revolutionary, the new methods look set to challenge radiologists' understanding of breast cancer and could alter their approach to imaging interpretation.Of thousands of pathology departments in the world, only a handful use "large-format pathology" in the breast. With large-format pathology, bigger continuous pieces of tissue are examined on supersized microscope slides with sophisticated 3D histology techniques.Whether conventional or advanced histology techniques are used, awareness is growing of the importance of cooperation between radiologists and pathologists in breast cancer management. These doctors must work closely together to match up pathology results with 2D and 3D imaging studies, make an assessment about the extent of disease, and provide accurate information for their colleagues in surgery.One course presenter, Dr. Tibor Tot, is a pioneer in large-format pathology, having almost 20 years of experience in the field. He recently published results from 500 consecutive breast carcinoma cases, reporting that only 34% of cases were unifocal, 36% were multifocal, and the others were diffuse or mixed (Cancer 2007;110:2551-2560). In contrast, conventional 2D pathology techniques have indicated the majority of breast cancer cases are unifocal."You see a microscopic tumor and believe there is only one focus, that the breast carcinoma is only a lump -- and that is wrong," said Tot, head of pathology and clinical cytology at the Central Hospital in Falun, Sweden.Information about disease extent has obvious importance for planning surgery. A lump can be excised in a lumpectomy, but breast-conserving surgery may not be appropriate for multifocal disease, given the frequency of post-treatment relapses.Instead, mastectomy may be a better option. Tot said that in his region, mastectomy is more common than in other settings because advanced pathology, which indicates more extensive disease, is routinely used. The large-format pathology findings match well to 3D imaging studies such as MRI, which also helps to show the true extent of disease.Researchers at Italy's University of Bologna, where large-format histology has been used in the breast for about seven years, recently reported that more than 50% of in situ and invasive lobular disease findings in 45 mastectomy cases was multifocal (Human Pathol 2007;38[12]:1736-1743). "Their results, similar to ours, show that multifocality and extensive lesions are very common in breast cancer. If an invasive tumor is multifocal, it has double the potential to give lymph node metastases," Tot said.The Italian researchers also noted that well-differentiated ductal carcinoma in situ grade 1 is often multifocal, while poorly differentiated DCIS grade 3 is more commonly unifocal.Tot speculates that breast disease often involves development of multiple foci in one sick lobe and that partial mastectomy to remove the sick lobe may be a viable option in these cases (Int J Surg Pathol 2007;15[4]369-375). According to this theory, it may be possible to prevent development of cancer in the future by removing a sick lobe before cancer develops.During the same session, Dr. Daniel Faverly will explain the microanatomy of the breast, including the significance of the terminal ductal lobular unit for breast imaging analysis, based on his experience with large-format pathology and conventional pathology techniques.

Faverly, comedical director at the CMP Pathology Laboratory in Brussels, will also review the four main types of calcifications:

  • calcium phosphate sediment (calcium milk)
  • calcium phosphate collagen deposit
  • calcium phosphate secretory psammomatous calcifications
  • calcium oxalate crystals

Some types of calcifications are strictly related to benign lesions, such as calcium oxalate, whereas others have been associated with borderline lesions or carcinoma in situ, he said.

Faverly plans to stress the importance of communication between radiologist and pathologist in both conventional and sophisticated pathology environments."Aspects of the lesion that the radiologist sees on a mammogram, sonography, or MRI should be compared routinely in daily practice with pathology findings. Radiologists can learn a lot more from comparing notes with pathologists than they can in a 30-minute course," Faverly said.After calcifications are detected on mammography, for example, a vacuum-assisted core needle biopsy is often performed. The pathologist should have an x-ray of the core for comparative purposes and must identify the number and distribution of calcifications and estimate lesion size. The radiologist and pathologist should then meet and discuss the results. Thanks to advances in communication technology, comparisons can easily be made across distances if the physicians are practicing at different facilities, he said.In some cases, the pathologist may find something in a specimen that is unexpected or inconsistent with the lesion type and may request additional views on mammography or a different imaging study, such as MRI. The radiomorphological comparisons help determine the true size of the lesion and tailor surgical treatment according to the patient's needs."This is really positive for your patient and also positive for the clinical team," Faverly said.The categorical course, "Breast: from basics to advanced imaging," runs from Friday until Tuesday 11 March.

Correlation between radiology and histology is proving vital for accurate assessment and appropriate management of breast cancer. In this case, vacuum-assisted needle core biopsy was performed following detection of microcalcifications. I: X-rays of cores demonstrate presence of calcifications. II: Sample of same area on 3D histology shows enlarged terminal ductal lobular unit still attached to collecting duct. III: High-magnification view of 2D standard histological section allows diagnosis of ductal carcinoma in situ (grade II according to Van Nuys classification). (Provided by D. Faverly)
   
Click for Power Point Presentation According to sick lobe theory, most breast carcinomas originate in a single sick breast lobe. Removal of the sick lobe in a partial mastectomy may be a good option in these cases. (Provided by T. Tot)

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