ductal carcinoma in situ shahla masood, m.d. professor of pathology university of florida college of...

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

Ductal Carcinoma In Situ

“DCIS is a heterogeneous disease characterized by neoplastic proliferation of ductal epithelial cells with no evidence of stromal invasion”

Atypical Ductal Hyperplasia

• Associated with moderate increase in breast cancer

risk

• Invasive cancer can occur anywhere in either breast

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

Distribution of DCIS in the Breast

• DCIS is a segmental disease

• Conservation therapy is justified in many patients with DCIS

Ductal Carcinoma In SituThe Facts:

• DCIS accounts for 30–40% of all mammographically-detected breast cancers

• The most frequent mammographic presentation is microcalcification

Ductal Carcinoma In Situ

Risk factors for local recurrence

• Morphologic features

• Size and extent of the lesion

• Adequacy of the excision

Ductal Carcinoma In Situ

• Morphologic Features– Traditional Classification

• Architectural Patterns» Comedo» Cribriform» Micropapillary» Papillary» Solid

Ductal Carcinoma In Situ

• Morphologic features

– Contemporary Classification:– Nuclear grade– Presence or absence of

necrosis

Ductal Carcinoma In SituAdequacy 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

Ductal Carcinoma In Situ

Treatment options• Local wide excision with and

without radiation therapy

• Mastectomy

Ductal Carcinoma In SituSize/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

Ductal Carcinoma In Situ

Classification System

• Clinically relevant

• Reproducible

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

Pathologic Evaluation of

Breast Specimens

Microscopic examination should include the following:

• Nuclear Grade:

• Necrosis: Absence or present

• Architectural pattern: comedo, cribriform, papillary, comedo, cribriform, papillary, micropapillary and solid.micropapillary and solid.

• Size (Extent of DCIS): the number of sections containing the number of sections containing

DCIS & the largest dimension of DCIS lesion on a glass DCIS & the largest dimension of DCIS lesion on a glass slide.slide.

• Margins of resection: Record closest margin as: Record closest margin as: >> 3-9 mm, 3-9 mm,

>> 10 mm or re-excision margin. 10 mm or re-excision margin.

• Calcifications: Correlate pathologic findings with specimenCorrelate pathologic findings with specimenx-ray and mammographic findings. x-ray and mammographic findings.

Ductal Carcinoma In Situ

Ductal Carcinoma In Situ

Low-grade DCISLow-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.

Low-grade

DCIS

Ductal Carcinoma In Situ High-grade DCIS

• Appearance: Markedly pleomorphicMarkedly pleomorphic

• Size: Nuclei usually >2.5 RBC or duct Nuclei usually >2.5 RBC or duct

epithelial cell epithelial cell

• Features: Usually vesicular and exhibit Usually vesicular and exhibit

irregular chromatin distribution and irregular chromatin distribution and

prominent, often multiple nucleoli. prominent, often multiple nucleoli.

Mitoses may be conspicuousMitoses may be conspicuous..

Ductal Carcinoma In Situ

Intermediate grade DCIS

Nuclei that are neither low-grade nor High-grade

““Excellent local control can be Excellent local control can be achieved without radiation achieved without radiation

therapy when margin widths' of therapy when margin widths' of at least 10 mm are obtained, at least 10 mm are obtained,

regardless of nuclear grade, the regardless of nuclear grade, the presence or absence of presence or absence of

comedonecrosis, or tumor size”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

NSABP-BI 7

(mean follow-up 90 mos)

8-yr Actuarial LR rates8-yr Actuarial LR rates

AllAll Non-invasiveNon-invasive lnvasivelnvasive

Excision Excision 26.8% 13.4% 13.4% 26.8% 13.4% 13.4%

Excision + RT Excision + RT 12.1% 8.2% 3.9% % 12.1% 8.2% 3.9% %

Reduction Reduction 55% 39% 71% 55% 39% 71%

EORTC - 10853

Median Follow-up 51 Months

1,010 Patients 1,010 Patients

Excision alone 16% Excision alone 16%

Excision + RT 9% Excision + RT 9%

% Reduction 44% % Reduction 44%

The Issue

To Radiate or Not Radiate?