1. Ductal Carcinoma In Situ Shahla Masood, M.D. Professor of Pathology University of Florida College of Medicine - Jacksonville Chief of Pathology and Laboratory Medicine Shands Jacksonville

2. Ductal Carcinoma In Situ “DCIS is a heterogeneous disease characterized by neoplastic proliferation of ductal epithelial cells with no evidence of stromal invasion”

3. Atypical Ductal Hyperplasia Associated with moderate increase in breast cancer risk Invasive cancer can occur anywhere in either breast

4. Distribution of DCIS in the Breast True multicentricity in DCIS is rare: – Holland and Hendriks/19 mastectomy specimen: in all but one case tumor was confined to a single “segment” of the breast – Faverly et al/60 mastectomy specimen: 90% of poorly differentiated DCIS grew in a continuous manner – Noguchi et al/clonal analysis by PCR: most DCIS is unifocal

6. Distribution of DCIS in the Breast DCIS is a segmental disease Conservation therapy is justified in many patients with DCIS

7. Ductal Carcinoma In Situ The Facts: DCIS accounts for 30–40% of all mammographically-detected breast cancers The most frequent mammographic presentation is microcalcification

8. Ductal Carcinoma In Situ Risk factors for local recurrence Morphologic features Size and extent of the lesion Adequacy of the excision

9. Ductal Carcinoma In Situ Morphologic Features – Traditional Classification Architectural Patterns » Comedo » Cribriform » Micropapillary » Papillary » Solid

10. Ductal Carcinoma In Situ Morphologic features – Contemporary Classification: –Nuclear grade –Presence or absence of necrosis

11. Ductal Carcinoma In Situ Adequacy of excision Margin width is an excellent predictor of local recurrence and the likelihood of residual tumor Mammograpic and pathologic evaluation is critical to determine the adequacy of the excision

12. Ductal Carcinoma In Situ Treatment options Local wide excision with and without radiation therapy Mastectomy

13. Ductal Carcinoma In Situ Size/Extent of the lesion Size is an important factor in selection of therapy: -Single histologic section: the largest diameter of the lesion -Multiple histologic sections: proportions of slides that show the lesion -Accurate assessment requires total and sequestial embedding of the lesion

14. Ductal Carcinoma In Situ Classification System Clinically relevant Reproducible

15. Molecular Biology of DCIS High grade lesions are often associated with unfavorable biological markers Loss of heterozygosity at various chromosomal loci differs according to DCIS pattern and grade There is no justification to perform biomarker studies in DCIS lesions in clinical practice

17. Pathologic Evaluation of Breast Specimens

18. Microscopic examination should include the following : Nuclear Grade: Necrosis: Absence or present comedo, cribriform, papillary, Architectural pattern: comedo, cribriform, papillary, micropapillary and solid. micropapillary and solid. the number of sections containing Size (Extent of DCIS): the number of sections containing DCIS & the largest dimension of DCIS lesion on a glass slide. DCIS & the largest dimension of DCIS lesion on a glass slide. Record closest margin as: > 3-9 mm, > 10 mm or re-excision margin. Margins of resection: Record closest margin as: > 3-9 mm, > 10 mm or re-excision margin. Correlate pathologic findings with specimen Calcifications: Correlate pathologic findings with specimen x-ray and mammographic findings. Ductal Carcinoma In Situ

19. Ductal Carcinoma In Situ Low-grade DCIS Appearance: Monotonous (monomorphic) Size: 1.5 - 2.0 normal RBC or duct epithelial cell nucleus dimensions Features: Usually exhibit diffuse, finely dispersed chromatin, only occasional nucleoli and mitotic figures.

20. Low-grade DCIS

21. Ductal Carcinoma In Situ High-grade DCIS Markedly pleomorphicAppearance: Markedly pleomorphic Nuclei usually >2.5 RBC or duct epithelial cellSize: Nuclei usually >2.5 RBC or duct epithelial cell Usually vesicular and exhibit irregular chromatin distribution and prominent, often multiple nucleoli. Mitoses may be conspicuous.Features: Usually vesicular and exhibit irregular chromatin distribution and prominent, often multiple nucleoli. Mitoses may be conspicuous.

22. Ductal Carcinoma In Situ Intermediate grade DCIS Nuclei that are neither low-grade nor High-grade

25. “Excellent local control can be achieved without radiation therapy when margin widths' of at least 10 mm are obtained, regardless of nuclear grade, the presence or absence of comedonecrosis, or tumor size” The Influence of Margin Width on Local Control of Ductal Carcinoma In Situ of The breast. Sliverstein et al, N Engl J Med 1999; 340:1455-61

26. NSABP-BI 7 (mean follow-up 90 mos) 8-yr Actuarial LR rates All Non-invasive lnvasive Excision 26.8% 13.4% 13.4% Excision + RT 12.1% 8.2% 3.9% % Reduction 55% 39% 71%

27. EORTC - 10853 Median Follow-up 51 Months 1,010 Patients Excision alone 16% Excision + RT 9% % Reduction 44%

28. The Issue To Radiate or Not Radiate?