College of American Pathologists protocol for the reporting of ductal carcinoma in situ.
Article Type: Report
Subject: Carcinoma, Ductal (Diagnosis)
Carcinoma, Ductal (Care and treatment)
Carcinoma, Ductal (Prognosis)
Authors: Lester, Susan C.
Connolly, James L.
Amin, Mahul B.
Pub Date: 01/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: Jan, 2009 Source Volume: 133 Source Issue: 1
Topic: Event Code: 350 Product standards, safety, & recalls
Organization: Organization: College of American Pathologists
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 230416958
Full Text: Ductal carcinoma in situ (DCIS) was a rare diagnosis before the introduction of screening mammography, but now composes 20% to 30% of all breast cancers. The development of appropriate guidelines for the care of women with DCIS has been challenging and controversial. (1) One obstacle to progress in this area has been variability in how DCIS is reported by pathologists. Although recommendations have been proposed, (2,3) reporting of some features of DCIS has not been consistent. (4,5) Published in this special section is the first College of American Pathologists (CAP) protocol for specimens with DCIS. The protocol provides a detailed guide for consistent reporting and was developed by the CAP Cancer Committee with guidance from a multidisciplinary Breast Cancer Review Panel that provides input to the Committee. Expert opinions are derived from disciplines of surgery, radiation oncology, medical oncology, and pathology. There are 12 required elements in the protocol: 6 for the type of specimen, 5 for diagnostic features, and 1 for appropriate American Joint Committee on Cancer stage designation. A protocol entirely focused on noninvasive carcinoma departs from the traditional role of the CAP Cancer Committee of providing protocols and checklists, but it was felt that consistent reporting of multiple, clinically relevant pathologic parameters in specimens for DCIS was necessary for clinical management of patients with this disease. This protocol is required for DCIS only in cases of complete excision, partial mastectomy, or mastectomy with or without axillary contents.

Nuclear grade, the presence of necrosis, and distance from margins are generally agreed to be the most important determinants of the likelihood of local recurrence and are routinely reported by most pathologists. The extent (size) of DCIS is also important for predicting the risk of local recurrence, the probability of residual cancer in the breast, the likelihood of close or involved margins, and the likelihood of finding, or missing, areas of invasion. (1,6-10) The extent of DCIS refers to the volume of breast tissue with ducts and lobules involved by DCIS. Because the ductal system is a complex 3-dimensional structure that rarely is grossly visible, a simple method to measure extent is not available. Indeed, precise measurement is not possible for several reasons. (11) The breast and its ductal system are highly compressible, as any woman who has undergone mammography can attest. Average breasts measuring 15 cm or more across are typically flattened to a width of 4 to 5 cm, or less, during mammography. Specimen radiography also compresses and distorts specimens. 12 Even in the absence of manual compression, breast specimens usually flatten, with the height of the specimen diminishing from the time the tissue is removed by the surgeon to the time it is measured by the pathologist. (13) In addition, gaps in ductal involvement are present in some cases of DCIS and may lead to underestimation of size. Finally, DCIS is often removed in multiple specimens, frequently as multiple reexcisions for residual disease, making the determination of overall original extent difficult, if not impossible.

Pathologists strive to report findings accurately, and the inability to be precise about the extent of DCIS may be one of the reasons that only 21% of reports had provided this information in 1 study. (4) However, the lack in the reporting of extent has hampered attempts to evaluate its importance in studies. In a European Organisation for Research and Treatment of Cancer study, only 25% of reports gave a size for DCIS. (5) In many cases, the "size" given was measured from a single slide--a method that will underestimate extent for all but the smallest cases.

Because extent of DCIS can range from 0.1 cm to involvement of all 4 quadrants of the breast, an estimation of extent can be important, even if precision cannot always be achieved. The optimal method to determine extent, in particular for specimens for which the diagnosis of DCIS has been established by prior core needle biopsy, is to serially section and completely submit all tissue in an orderly fashion to enable retrospective mapping of the areas involved by DCIS (the serial sequential sampling method, or SSS). However, because extent is a required reporting element, a method was needed that could be applied to all specimens, regardless of the method used for processing the specimen. Two studies were initiated to compare the SSS method with other methods of estimating extent and are published in this special section. (14,15) The common method of assessing size from 1 slide was clearly shown to underestimate extent in most cases and should not be used except for cases in which DCIS is only present in 1 block. (15) The number of blocks with DCIS multiplied by the width of a tissue section was shown to correlate with size, as determined by the SSS method. (14,15) Both studies demonstrated that a multiplier of 0.3 cm underestimates extent. Using 0.4 cm, or a larger multiplier if the width of tissue sections is known, gives a better estimate of size. The correlation is best for DCIS with an extent less than 2 cm and poorer when extent is greater than 4 cm. It is important to consider that these 2 methods are not expected to give identical results. The measurements will be most similar when the DCIS is present in a predominantly linear pattern. The block method will yield larger estimates of extent when the DCIS occupies a larger area in 3 dimensions, because the number of involved blocks is increased by volume as well as by greatest linear dimension. However, the median extent of DCIS reported for patients is 2 to 3 cm and only 10% to 20% of cases are in the category of 4 cm or more. Many women with large areas of DCIS will have residual DCIS on excision and most will probably require mastectomy for widely clear margins. In addition to the SSS and block methods, other means of assessing the extent of DCIS will be applicable for some types of specimens (eg, if opposing margins are involved, the size of the specimen may be used). Ultimately, additional studies will be necessary to determine if a specific method is better for predicting residual disease or local recurrence or if any estimate of extent is sufficient.

We welcome additional commentary on this protocol as pathologists implement it in their practice. Numerous studies are underway to ascertain additional prognostic factors for DCIS.16 We are optimistic that other pathologic features, including molecular markers, will be identified in the future to aid in identifying those women most likely to progress to invasive carcinoma. As with all CAP Cancer Committee protocols, as such information becomes available, it will be incorporated into protocols to keep them continually updated and clinically relevant.

Accepted for publication September 18, 2008.

References

(1.) O'Sullivan MJ, Morrow M. Ductal carcinoma in situ--current management. Surg Clin North Am. 2007;87:333-351, viii.

(2.) Association of Directors of Anatomic and Surgical Pathology. Recommendations for the Reporting of Breast Carcinoma. Updated September 2004,Version 1.1. Available at: http://www.adasp.org/Checklists/Checklists.htm. Accessed September 18, 2008.

(3.) Schwartz GF, Lagios MD, Carter D, et al. Consensus conference on the classification of ductal carcinoma in situ. Cancer. 1997;80:1798-1802.

(4.) Apple SK. Variability in gross and microscopic pathology reporting in excisional biopsies of breast cancer tissue. Breast J. 2006;12:145-149.

(5.) Bijker N, Meijnen P, Peterse JL, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24:3381-3387.

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(8.) Di Saverio S, Catena F, Santini D, et al. 259 patients with DCIS of the breast applying USC/Van Nuys prognostic index: a retrospective review with long term follow up. Breast Cancer Res Treat. 2008;109:404-416.

(9.) MacDonald HR, Silverstein MJ, Mabry H, et al. Local control in ductal carcinoma in situ treated by excision alone: incremental benefit of larger margins. Am J Surg. 2005;190:521-525.

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(11.) Saqi A, Osborne MP, Rosenblatt R, Shin SJ, Hoda SA. Quantifying mammary duct carcinoma in situ: a wild-goose chase? Am J Clin Pathol. 2000; 113(suppl 1):S30-S37.

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(13.) Graham RA, Homer MJ, Katz J, et al. The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer. Am J Surg. 2002;184:89-93.

(14.) Dadmanesh F, Fan X, Dastane A, Amin MB, Bose S. Comparative analysis of size estimation by mapping and counting number of blocks with ductal carcinoma in situ in breast excision specimens. Arch Pathol Lab Med. 2009;133:26-30.

(15.) Grin A, Horne G, Ennis M, O'Malley FP. Measuring extent of ductal carcinoma in situ in breast excision specimens: a comparison of 4 methods. Arch Pathol Lab Med. 2009;133:31-37.

(16.) Gauthier ML, Berman HK, Miller C, et al. Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors. Cancer Cell. 2007;12:479-491.

Susan C. Lester, MD, PhD; James L. Connolly, MD; Mahul B. Amin, MD

From the Department of Pathology, Brigham and Women's Hospital (Dr Lester) and the Department of Pathology, Beth Israel Deaconess Medical Center (Dr Connolly), Boston, Mass; and the Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif (Dr Amin).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Mahul B. Amin, MD, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 8728, Los Angeles, CA 90048 (e-mail: aminm@cshs.org).
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