1. Appropriate Sampling of Lumpectomy Specimens
Carol L. Schiller, M.D.
Midwest Diagnostic Pathology, Advocate Condell Medical Center
July 20, 2010

2. Why Do Breast People Want to Put Through So Many Darn Sections?
Carol L. Schiller, M.D.
Midwest Diagnostic Pathology, Advocate Condell Medical Center
July 20, 2010

3. Appropriate Sampling of Lumpectomy Specimens
Carol L. Schiller, M.D.
Midwest Diagnostic Pathology, Advocate Condell Medical Center
July 20, 2010

4. Objectives
Outline available recommendations (though notably limited), expectations of “breast community” for optimal processing of lumpectomy (less than total mastectomy) specimens
Sampling: How much? Why?
Discuss at least a rough standard framework / protocol amongst sites
Provide adequate and appropriate information for patient management decisions
Foster optimal resident teaching
Try to explain why breast people want to put through so many sections

5. Some things should be easy to agree on (right?)
Know history
Orient
Weigh
Measure in three dimensions
Ink
Slice
Describe
Sample (ahhh, here comes the conflict)

6. Before You Cut… Know history Palpable mass Mammographic findings
Distortion
Calcifications
Size/extent/additional imaging modalities (MRI)
Prior biopsy findings (date, multiple)
If biopsy more than three months ago, is this post-neoadjuvant?

7. Before You Cut… Orientation Specimen imaging
Per CAP: “Mammography or ultrasound should be used to document the presence of the targeted lesion in the excised tissue”
“The specimen radiograph (if performed) and the results of the radiologic evaluation should be available to the pathologist.”
Unoriented needle loc’s: Can’t assume orientation based on needle or grid
Surgeon orientation must include two perpendicular references to be of value
If surgeon attempted to orient but it doesn’t make sense to you, call immediately

8. Before You Cut… Weigh Measure in three dimensions Ink
If specimen is oriented, measurements should be oriented
Ink
Area indicated on mammography grid
Inking may roughly help direct sampling (only indicates the tissue slices, not the blocks likely to contain mammographic area of interest)
Make sure doesn’t interfere with clear delineation of the six sides of the specimen

9. Before You Cut… Ink: Six colors vs. four colors
Advantage of six: Same every time, avoids confusion
Four: Variable, changes with orientation/direction of slicing
If six, best to have a standard
Superior = blue (sky)
Inferior = green (grass)
Lateral = yellow (l’s)
Medial = red (med rhymes with red)
Deep = black (dirt is deeper than grass)
Anterior/Superficial = orange (it’s what’s left)

10. Get Cutting Slice and lay out sequentially Describe Sample
Mass, measurements
Biopsy site(s), presence/shape of clip(s)/clip housing material, tissue slice from which clip recovered
Percentage of fatty vs. fibroglandular (“white”) breast tissue
Measurment of gross distance to at least closest margins
Sample

11. Sampling Published guidelines very limited
Commercial grossing manuals
Individual grossing protocols/Anecdotal practices from larger breast centers, cancer centers
Guidelines from professional organizations (pathology, multidisciplinary)
Differ based on targeted lesion
Palpable mass
Image detected mass/distortion
Image detected calcifications

12. Image Detected Lesions (Ca++)
Lester, Susan C (Manual of Surgical Pathology, 2nd ed):
Entirely submit if can fit in 20 blocks or less; If entire specimen not submitted, include statement estimating %age of specimen submitted
High suspicion or prior dx of DCIS or ADH on core:
Completely submit all tissue containing mammographic calcifications and adjacent tissue
All fibrous tissue (if feasible)
At least two perpendicular sections of each of 6 margins

13. Image Detected Lesions (Ca++)
Lester (cont.)
Low suspicion lesion:
Completely submit all tissue containing calcifications
Adjacent tissue on either side
2 perpendicular sections of each 6 margins
Keep remaining slices in order/maintain orientation; If blocks of calcifications have ADH or DCIS, all additional fibrous tissue should be examined microscopically

14. Image Detected Lesions (Ca++)
Rosai (Rosai and Ackerman’s Surgical Pathology, 9th ed): “at least two thirds of the breast tissue (exclusive of adipose tissue) should be processed”
National Consortium of Breast Centers, certain institutional protocols (e.g. UCLA): Entirely submit if specimen </= 5 cm in greatest dimension
Northwestern:
Entirely submit if </= 30 cassettes
If too big to entirely submit, residents required to call attending or breast fellow to guide sampling

15. Arch Pathol Lab Med – Vol 133; January 2009. pp. 15-25.

16. CAP DCIS Protocol
Clinical or radiologic lesion for which surgery was performed must be examined microscopically
When known diagnosis of DCIS (eg, by prior core needle biopsy): highly recommended entire specimen be examined by using serial sequential sampling to…
exclude the possibility of invasion
completely evaluate the margins
aid in determining extent
If not possible, at least the entire region of the targeted lesion should be examined microscopically (note approx. % of specimen sampled)
Sample, at a minimum, mammographically negative breast tissue flanking areas of calcification to be certain the entire extent of the lesion is represented
If DCIS, LCIS or ADH is identified, all fibrous tissue should be examined
All other gross lesions in the specimen must be sampled
Margins should be evaluated
-CAP: ink on DCIS for margin to be “positive”
-NCCN: margins less than 0.1 cm inadequate
-CAP: when margins positive
Focal (eg, DCIS at the margin in a <0.1 cm area in 1 block)
Minimal/moderate (between focal and extensive)
Extensive (eg, DCIS at the margin in an area >/= 1.5 cm or in 5 or more low-power fields and/or in 8 or more blocks)

17. Excisions for DCIS Determinants of likelihood of local recurrence
Nuclear grade
Presence of Necrosis
Distance from Margins
Extent (size) of DCIS
Predicting risk of local recurrence
Probability of residual cancer in the breast
Likelihood of close or involved margins
Likelihood of finding, or missing, areas of invasion

18. Arch Pathol Lab Med – Vol 133; January 2009. pp. 15-25.

19. Extent of DCIS Often not recorded Difficult to measure
Series of outside slide review: only 21% of cases reported the size of DCIS (Apple SK. Variability in gross and microscopic pathology reporting in excisional biopsies of breast cancer tissue. Breast J. 2006;12: )
Most measurements were given as the largest dimension measured on a single slide
Difficult to measure
Mammographic extent often doesn’t correlate with microscopic extent
No gross lesion
Complexity of ductal system; Compressibility of breast tissue
No standardized method for estimating the extent of DCIS

20. Methods for measuring extent of DCIS
Single slide method:
Underestimates extent in almost all cases when DCIS is greater than 1 cm
Should only be used when DCIS is present in only one slide

21. Methods for measuring extent of DCIS
Margins
If DCIS involves two opposing margins, distance between margins can be used as extent of DCIS in the specimen
Doesn’t happen often
Arch Pathol Lab Med – Vol 133; January pp

22. Methods for measuring extent of DCIS
Non-sequential sampling (block counting)
Multiply #of blocks with DCIS by 0.4 cm
Frequently underestimates extent
Can overestimate, eg when DCIS is present in high volume (3-D) rather than predominantly linear distribution
Arch Pathol Lab Med – Vol 133; January pp

23. Methods for measuring extent of DCIS
Serial sequential sampling (mapping) method
Preferred method by CAP, esp. if excision of known DCIS (largely because of substantial underestimation and overestimation by other methods)
Routinely used in numerous breast centers (M.D. Anderson, Mayo, etc.)
Arch Pathol Lab Med – Vol 133; January pp

24. Methods for measuring extent of DCIS
Serial sequential sampling (mapping) method
Entire specimen sectioned in sequence and block locations recorded
Sliced specimen radiograph, block location marked on radiograph itself, correlates calcifications with block location
Simple specimen diagram without sliced radiograph
Calculate
Average slice thickness = length of specimen/number of slices
Size of DCIS = Number of consecutive slices involved X average slice thickness

25. Comparison of Methods for Measuring Extent of DCIS
O’Malley (Mt. Sinai Hospital, Ontario, Canada)
Compared (78 cases):
Serial sequential sampling
Calculation based on location of calcifications in specimen radiograph
Non-sequential sampling (block method, using 0.3 cm)
Single slide
Mean number of blocks submitted per case: 26.7 (range, 8-66)
Arch Pathol Lab Med – Vol 133; January pp

26. Comparison of Methods for Measuring Extent of DCIS
O’Malley (Mt. Sinai Hospital, Ontario, Canada)
Results
All 3 alternative methods tended to underestimate DCIS
Discrepancies more pronounced as size increased
Difference as compared to SSS of 1 cm or less: 81%, 72%, 50% (Ca++, block, single slide)
Difference of >2cm: 9%, 8%, 30%
Arch Pathol Lab Med – Vol 133; January pp

27. - 18 slices Circles = Ca++ X = block with DCIS
Sectioned mediolateral plane (specimen size 5.7 cm/18 slices = 0.3 avg. slice thickness)
0.3 cm x 8 slices = 2.4 cm
Arch Pathol Lab Med – Vol 133; January pp

28. Comparison of Methods for Measuring Extent of DCIS
Bose, et al (Cedars-Sinai Medical Center, LA)
98 cases
Compared mapping method to block method (using 0.3 cm, 0.35 cm, 0.4 cm and 0.5 cm as the multiplier)
Results
Block method underestimated size in 71 cases (72%), by 4.5% to 81.3% (mean, 33%)
Best concordance using 0.4 cm as the multiplier
Arch Pathol Lab Med – Vol 133; January pp

29. Diagram extremely important in both selective and complete sampling
Only way specimen can be reconstructed to accurately measure the size of DCIS

30. Excisions for MRI Detected Lesions
When lesion detected only by MRI
CAP recommends to entirely submit specimen for histologic examination
No way of knowing if selective sampling encompasses the targeted lesion because radiographic specimen is of no value

31. Excisions For Mass Lesion
Even less available in terms of published recommendations, but less debate
Lester:
Mass – Four to five cassettes of possible carcinomas, or 1 section per cm for other grossly evident masses
In the absence of an identified mass, all fibrous breast tissue is submitted
Margins – up to 12 perpendicular sections representing each of the six margins for oriented specimens suspicious for carcinoma or known to have carcinoma
Normal tissue – At least one cassette of representative fibrous tissue if not present in the slides above

32. CAP Protocol For Invasive Breast Carcinoma
Specimen sampling for specimens with invasive carcinoma has the following goals:
Clinical or radiologic lesion for which surgery was performed must be examined microscopically
If the lesion is a nonpalpable imaging finding, the specimen radiograph and/or additional radiologic studies may be necessary to identify the lesion
When practical, the entire lesion, or the entire area with the imaging finding, should be submitted in a sequential fashion for histologic examination

33. CAP Protocol For Invasive Breast Carcinoma
Continued:
If specimen consists predominantly of DCIS with microinvasion, complete submission of the entire specimen, or at a minimum the entire grossly involved area, is recommended to identify additional areas of invasion and/or lymph-vascular invasion
All other gross lesions in the specimen must be sampled
Each designated margin must be evaluated for involvement by invasive carcinoma and DCIS

34. What I Do
Always use a specimen diagram, regardless of reason for excision
Always submit entirely if it will fit in 30 cassettes or less, regardless of reason for excision

35. What I Do When Not Feasible To Entirely Submit
For mass lesion
Submit at a minimum…
Both ends entirely, perpendicularly sectioned
At least 1 section per cm of mass
At least one section from each tissue slice with mass and at least one section from flanking slices
(In reality, when tumor 2 cm or less, I generally entirely submit all slices with tumor and the two flanking slices)
At least one section from each remaining slice that has any fibrous tissue in it (include margin whenever close)
Above sections to include at least 2 perpendicular sections of each margin

36. What I Do When Not Feasible To Entirely Submit
For mammographic calcifications
Submit at a minimum…
Both ends entirely, perpendicularly sectioned
Entirely submit all slices with lesion (slices indicated by grid, slices with biopsy site)
Entirely submit two flanking slices
All fibrous tissue if possible; at least one or more section of fibrous tissue per slice (each slice should be sampled)
Above sections to include at least 2 perpendicular sections of each margin

37. Thank You!