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Invasive Carcinoma II - Breast
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III. MICROSCOPIC PATHOLOGY
A. Histologic Grade
Microscopic architecture (growth patterns) in the majority of infiltrating carcinomas are variable and often mixed, although a particular pattern may predominate. The architecture reflects the degree of differentiation. Tubules, cribriform glands, irregular glands, papillae and acini (Slide 6) occur in well-differentiated tumors. Cords are common in intermediate grade of tumors (Slide 7). Solid nests and sheets predominate in poorly-differentiated neoplasms (Slides 8 and 9).
- The nuclear grade is determined by:
- 1. Uniformity or irregularity of nuclear size and shape
- 2. Chromatin particle size (finely or coarsely granular) and distribution (even or uneven)
- 3. Nucleoli (size and frequency)
- 4. Mitotic activity.
In general, there is a good correlation between the architecture and the nuclear features. Those well-differentiated tumors have predominantly glands and uniform tumor cells with small nuclei, fine chromatin, inconspicuous nucleoli and low mitotic activity. Whereas poorly differentiated tumors have mostly nests and sheets present with large, irregular nuclei, coarse chromatin, prominent nucleoli and high mitotic activity. Moderately differentiated neoplasms are intermediate between the two groups.
Because of the heterogeneity within the same tumor, it would be advantageous to adopt a uniform, reproducible system that correlates with prognosis. The Bloom/Richardson (Elston Modified) grading method is one such system. It combines the architecture and nuclear scores into a final histologic grade. This System is recommended for all invasive carcinomas (Page et al).
BLOOM/RICHARDSON (ELSTON MOD.) GRADING METHOD Tubular Formation Score Majority of tumor (>75%) 1 Moderate Degree (10-75%) 2 Little or none (<10%) 3 Nuclear Pleomorphism Score Uniform Cells (size is not criterion) 1 Slide 10 Moderate Increase in Variability 2 Slide 11 Marked Variation (Often large nucleoli) 3 Slide 12 Mitotic Counts (per 10 high power fields) Score Low (0-5 mitotic figures) 1 Moderate (6-10 mitotic figures) 2 High (>11 mitotic figures) 3 FINAL GRADE Score Grade I, Well differentiated 3-5 points Grade II, Moderately differentiated 6-7 points Grade III, Poorly differentiated 8-9 points
B. Stromal Changes
These include desmoplastic reaction with proliferation of newly formed fibroblasts in an edematous, myxomatous or highly collagenized matrix. In the background, elastosis also occurs (Slide 13). The number of lymphocytes, plasma cells and histiocytes is variable.
C. Vascular Lymphatic Space Invasion
This feature should be carefully evaluated and reported. Shrinkage artefact due to fixation produces an empty space between the tumor nest and fibrous stroma. This space is often mis-interpreted as vascular lymphatic space (Slide 14). A true vascular lymphatic space clearly lined by clearly recognizible endothelial cells (Slide 15). This invasion is most readily seen in the periphery of the tumor and beyond. Less commonly, the tumor cells invade the blood vessels and perineural spaces.
Studies have demonstrated that the presence of vascular lymphatic space invasion increases tumor recurrence. The study of Rosen et al further reveals that invasion of the lymphatics, capillaries and blood vessels (Slide 16) in tumors up to 2 cm in size with or without lymph node metastases increases death rate, when compared to comparable tumors without such a finding (Rosen PP et al, 1981). Perineural space invasion does not have prognostic significance by itself.
D. Infiltrating Ductal Carcinoma with Extensive Intraductal Component (EIC)
Within the infiltrating ductal carcinoma, the intraductal carcinoma may be extensive or completely absent. It is important to assess the amount of intraductal carcinoma. Extensive intraductal component (EIC) positive tumors include the following conditions.
- 1. Predominantly invasive carcinoma containing DCIS in more than 25% of tumor (Slide 17)
- 2. Predominantly DCIS with focal invasion, and DCIS extends beyond the borders of invasive carcinoma
When treated by conservative surgery and radiotherapy, these EIC positive tumors are more likely to recur than EIC negative tumors. Based on data from Joint Center for Radiation Therapy, 28% of recurrent infiltrating ductal carcinomas are EIC positive. Five-year actuarial local recurrence rate is 6% and 24% for EIC negative and positive tumors, respectively.
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