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

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

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

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

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)

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?

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

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

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)

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

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

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

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

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

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

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)

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

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

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;12:145-149) 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

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

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 2009. pp. 15-25.

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 2009. pp. 15-25.

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 2009. pp. 15-25.

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

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 2009. pp. 31-37.

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 2009. pp. 31-37.

- 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 2009. pp. 31-37.

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 2009. pp. 26-30.

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

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

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

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

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

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

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

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

Thank You!