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Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT) but offers a significant reduction in reoperation. In this study a technique to allow for more effective freezing of breast tissue was developed to perform FS of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center (ASC). FS of sentinel lymph node biopsies were performed concurrently. 181 study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. The majority of the decrease in reoperative rate was due to a decrease in the need for margin reexcision. The number of patients requiring one, two, or three operations to complete therapy were 84, 92, and 12, and 146, 33, and 2 in the control and study groups respectively. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for BCT patients.
Patients undergoing breast conserving therapy (BCT) for early stage breast carcinoma have outcomes comparable to patients undergoing mastectomy given adequate surgical margin status and appropriate radiation therapy [1–5]. Factors influencing reoperation rates include axillary staging procedures, completion axillary lymph node dissection (cALND), and/or margin reexcision. Achieving acceptable margin status may be challenging due to non-palpable or subtle breast disease, extent of disease, and the degree of commitment of the surgeon and patient to conservative therapy. These factors and variable definitions for inadequate (close) margins have resulted in variable but often high reexcision rates, ranging from 20–70%. Reoperation results in increased healthcare costs, inconvenience and increased risks to the patient, and delays to subsequent radiation and other adjuvant therapy [1–20].
Intraoperative pathology consultation for sentinel lymph node (SLN) and lumpectomy specimens can decrease the need for reoperation by allowing surgeons to resect additional breast tissue and/or perform cALND during the initial breast cancer operation. Many institutions offer intraoperative SLN assessment for patients undergoing BCT. Most, however, do not offer intraoperative analysis of lumpectomy specimens and even fewer offer frozen section analysis of margins (FSM) for these specimens, largely due to technical limitations when using standard frozen section techniques. Margin reexcision is the most common indication for reoperation in patients undergoing BCT . Reexcision for close or positive margins will likely increase in relative importance as cALND rates decline as a result of recent reports of questionable significance of micrometastatic axillary disease [22–25]. This report outlines the development of an intraoperative frozen section (FS) practice providing both SLN and FSM evaluation at a free-standing ambulatory care center and examines its impact on patient care during its first year.
The majority of breast surgical oncology services at the University of Michigan were relocated to an ambulatory surgical center (ASC) in April 2008. A pathology laboratory was designed to support pathology services at our ASC with a focus on developing a FS practice to reduce reoperation rates for patients undergoing BCT. The pathology laboratory was designed and built according to OSHA standards and was equipped with standard facilities for specimen storage; stations for accessioning, grossing and cryostat cutting; as well as a slide review area. The frozen section laboratory at the ASC opened in August of 2009.
Patients were selected from all patients undergoing BCT at our ASC between August 2008 and July 2010. Eligible patients had a previous pathologic diagnosis of invasive or in situ carcinoma who based on clinical and radiographic evaluation were candidates for BCT.
The study group comprised all BCT patients who underwent FSM and/or SLN FS analysis from August 2009 through July 2010. The study group included patients who had undergone neoadjuvant therapy as well as patients undergoing a designed 2-step procedure due to either a need for axillary staging prior to chemotherapy or referral from an outside institution for inadequate margin status. Patients offered SLN FS were those with a previous diagnosis of invasive carcinoma or extensive high grade DCIS with unknown SLN status at the time of surgery. Patients with an invasive carcinoma ≥1 cm routinely underwent preoperative axillary staging via ultrasound and fine needle aspiration (FNA) of any suspicious lymph nodes. Any patient with a positive FNA preoperatively did not undergo SLN FS.
Patients included in the control group were all those who underwent BCT without the assistance of FS analysis at the same ASC from August 2008 through July 2009, in the year prior to the opening of the FS laboratory.
SLN were first dissected from adipose tissue, sectioned at 2 mm intervals, and entirely submitted for FS evaluation. Tissue sections were completely embedded and frozen within Optimal Cutting Tissue (OCT) media and cut on a standard −20°C cryostat, creating sections 6–7 microns in thickness. At least two levels of each tissue block were evaluated at the time of FS analysis. Any metastatic tumor >0.2 mm was reported to the surgeon as at this time any micrometastatic tumor deposit was considered clinically significant. If SLN FS analysis triggered cALND prior to completion of FS analysis of all SLNB specimens, FS analysis on subsequent SLNB specimens was cancelled and these were submitted for permanent section (PS) evaluation only.
All SLNB tissue blocks were then processed for PS evaluation via standard protocol which at our institution entailed pathologist evaluation of four H&E-stained levels.
FSM was performed on all lumpectomy and reexcision lumpectomy specimens, including those with and without wire localization. Mammographic films of the specimen (when applicable) were delivered to the pathology laboratory along with the specimen. The specimen was oriented using orienting sutures and/or with assistance by the surgeon and margins were inked. The specimen was sectioned at 3–4 mm intervals along the long axis and examined by a pathology assistant and pathologist. Sections were submitted for FSM for all grossly suspicious margins. The number of sections varied from case to case but some tissue was submitted for FS evaluation in all cases. In general 2–3 radial sections were taken for highly suspicious margins in which tumor or fibrous tissue extending from tumor were within 5 mm of the margin and at least one radial section was submitted if any suspicious tissue was present within 2 cm of the margin. Sections were not routinely submitted for FSM if the tissue at a margin was grossly unremarkable and >2 cm from any identifiable tumor, biopsy site, or other lesion. Areas of fibrous tissue adjacent to a margin not associated with an obvious tumor, biopsy site, or otherwise grossly suspicious lesion were sampled variably for FSM depending on pathologic findings both in the prior biopsy and current specimen. More sections were typically submitted for FSM in patients who had undergone previous excisional biopsy or lumpectomy, received prior chemotherapy, had extensive or exclusively intraductal disease, or were known to have multifocal disease (identified via pre-operative imaging or pathology) in which potential neoplastic tissue was much more difficult to appreciate grossly. In patients with known multifocal disease we correlated the specimen with prior radiologic and pathology reports and with accompanying specimen radiographs, attempted to grossly identify all tumors, and assess margins for each. For reexcision of individual margins in which biopsy site but no discrete tumor was identified, at least 3 sections of each margin were submitted for FS evaluation.
Once selected for FS, a tissue section was placed on a cryostat chuck with a minimal amount of OCT media (just enough OCT to adhere the tissue to the chuck) and immersed in liquid nitrogen (−196°C) for 10–15 seconds until the tissue was completely frozen. Due to the difficulty in sectioning fatty tissue, thicker sections than those typically used for FS (16–20 µm thick) were then cut on a standard cryostat (−20°C). At least two sections from each block were placed on plus slides, stained with a rapid H&E technique, coverslipped, and reviewed by the pathologist (Figure 1). Additional H&E-stained levels were cut and/or additional tissue sections were evaluated via FS based on communication of findings between the pathologist, pathology assistant, and histotechnologist.
A margin was considered positive if tumor (either invasive carcinoma or DCIS) extended to the inked margin and close if DCIS extended to within 3 mm of the margin and/or invasive carcinoma extended to within 2 mm of the margin (Figure 2). In difficult cases in which the pathologist was uncertain whether atypical ductal hyperplasia (ADH) or DCIS was extending to/close to a margin, atypical ducts extending to/close to the margin was reported, and the uncertainty conveyed to the surgeon. In the majority of cases a report of any positive or close margin prompted immediate surgical reexcision of that margin. Intraoperatively reexcised margin specimens were infrequently submitted for FSM at the discretion of the surgeon. Reasons for which surgeons did not submit intraoperatively reexcised margins for FSM varied but included time constraints, consideration of cosmetic outcome and patient preference. Surgeons were more likely to send intraoperatively reexcised margins for FSM if the original FS diagnosis had indicated a positive as opposed to a close margin and if resection of additional tissue would not significantly compromise cosmetic outcome. Intraoperatively reexcised specimens were evaluated using a minimum of 3 representative sections for each margin. All FS blocks were then processed for PS evaluation. Additional tissue blocks from both the main lumpectomy specimen and any intraoperatively reexcised margin specimens were also submitted for PS evaluation.
Clinicopathologic features were summarized for study and control groups using means, medians and frequencies. Comparisons between the two groups were assessed using two-sample t-tests for continuous factors and chi-square tests for categorical factors. For tissue sections that were selected for FS, a false negative (FN) was defined as a negative margin in at least one of the six regions of the FS and a close or positive margin in the same region of the PS. Likewise, a true negative (TN) or true positive (TP) was defined as either negative or positive margins on FS, respectively, which were confirmed on PS. A false positive (FP) was defined as any margin meeting all of the following criteria: 1) the margin was interpreted as close or positive at FS; 2) upon review of correlative PS slides the focus of carcinoma was >1 mm further from the margin than reported on FS; and 3) using the distance identified on PS slides and per margin definitions outlined above the margin would be interpreted as negative. For SLN analysis a FN was defined as that deemed negative on FS found to be positive on PS. SLN TP and TN were those whose results on FS were confirmed on PS. SLN FS and FSM TN, FN, TP and FP were described using counts and frequencies. Comparisons of clinicopathologic features between patients with a FSM FN versus those without a FN were conducted similar to the study and control group analysis described above. The effect of FSM implementation on the outcome of additional surgery was analyzed using a multivariable logistic model controlling for clinicopathologic factors. Number of blocks submitted for FS was regressed on turn-around-time using a linear regression model. All analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC).
One hundred seventy eight patients underwent SLN FS analysis; seventy two (40.4%) had SLN FS alone and 106 (59.6%) had both FSM and SLN FS during the same surgery. There were 31 (17.4%) TP, 144 (80.9%) TN, 3 (1.7%) FN and no FP results. The 31 TP patients all underwent immediate cALND. Among the TN cases there were 5 which had foci of isolated tumor cells (<0.2 mm) not reported at the time of FS. No patients in this group later underwent cALND. The 3 FN cases consisted of 2 with micrometastases (>0.2 mm but <2 mm) of ductal carcinoma, both present only in the routinely processed PS slides and not identified on re-review of the FS slides and one patient with macrometastatic (>2 mm) lobular carcinoma that was confirmed to have tumor present in FS slides upon re-review. All 3 FN patients later underwent cALND, none of which had additional metastatic axillary disease.
One hundred eighty one patients underwent 189 surgical procedures utilizing FSM, of which 75 (41.4%) had FSM alone and 106 (58.6%) had both FSM and SLN FS analysis during the same surgery. There were 188 control patients who did not undergo FSM, of which 77 (41.0%) had lumpectomy alone and 111 (59.0%) had lumpectomy and SLNB. As is typical of patients deemed eligible for BCT the majority in both study and control groups were more likely to have lower stage (T1 or T2) disease and an identifiable mass on pre-operative imaging than non-eligible patients. However, as demonstrated in Table 1, there were no statistically significant differences in clinicopathologic features between study and control groups and therefore there was no selection bias in comparing results between the two groups.
An average of 5.9 FS blocks per lumpectomy (range 1–11), 8.3 FS blocks per case (range 1–27), and 18.4 additional PS blocks per case (range 0–35) were performed. There was no significant association between close/positive margin(s) and margin location. Close/positive margin(s) were ultimately identified in 112 of 189 (59.3%) surgical specimens sent for FSM. One or more margins were reexcised in 133 of 189 (70.4%). In the majority of cases reexcision of margins was driven by FS report of close/positive margins but was also influenced by specimen radiography findings and surgical judgment. Intraoperatively reexcised margins were sent for FSM in 28/133 cases (21.1%).
In the control group, the reoperation rate was 55.3% with 92 (48.9%) requiring a second operation and 12 (6.4%) requiring a third operation to complete surgical therapy. Within this group 72 (38.3%) required additional surgery for margin revision only, 6 (3.2%) for cALND only, 3 (1.6%) for SLNB only (due to unexpected invasive carcinoma present in the lumpectomy); and 23 (12.2%) for both margin revision and axillary surgery.
In the study group, the reoperation rate was 19.3% with 33 (18.2%) undergoing a second operation and 2 (1.1%) proceeding to a third operation to compete surgical therapy. Indications for patient reoperation were 27 (14.9%) requiring margin revision only, 4 (2.2%) cALND only, and 3 (1.7%) SLNB only. One patient subsequently underwent elective mastectomy despite a negative margin status on lumpectomy; no residual carcinoma was identified in this specimen (Figure 3).
Of the 27 patients requiring margin revision 16 (59.3%) underwent reexcision lumpectomy, and 11 (40.7%) proceeded directly to mastectomy. Of the two patients who required a third surgery to complete therapy one underwent two additional reexcision lumpectomies, and the other a reexcision lumpectomy and ultimately mastectomy. In both of these cases the initial reexcision lumpectomy was submitted for FSM, and both pathology sampling error and intraoperatively re-excised close/positive margins sent only for PS resulted in the need for a third surgery. Overall there were statistically significant declines in reoperation and reexcision between control and study groups (p < 0.0001). Rate of conversion to mastectomy was also reduced but did not reach statistical significance (p=0.0961) (Figure 4).
The decrease in reoperative rates was largely attributed to the addition of FSM, not FS SLN, since the majority of the drop in reexcision rate was due to a large decrease in number of patients who had to undergo reexcision of margins, alone or jointly with other procedures (95 patients in the control group versus 27 patients in the study group). In fact, the number of patients who needed to undergo reoperation for additional axillary surgery alone was similar in the study and control groups (7 patients in the control group versus 9 patients in the study group) (Figure 3). Most of the patients with positive SLNB also had close/positive margins in both control and study groups (15/21 in the control group, 17/21 in the study group). Among patients who underwent both FSM and FS SLN only 5 out of 106 (4.7%) study patients benefited from and only 7 out of 111 (6.3%) control patients would have benefited from SLN FS analysis alone (assuming perfect pathology performance). This is likely influenced by stringent preoperative evaluation with axillary ultrasound and FNA which identifies many node positive patients who would have otherwise been identified by sentinel node biopsy.
Reasons for failure of FSM to prevent reoperation (FN cases) were divided into the following categories: 1) final close/positive margins limited to the intraoperatively reexcised specimens sent for PS evaluation only; 2) pathologist analytical errors 3) cessation of the procedure due to disease extent that was greater than anticipated; and 4) a combination of multiple factors (Figure 5).
The majority of FN cases had close/positive intraoperatively reexcised margins that were submitted for PS only, and/or had close/positive margins which were not adequately sampled at time of FS. Sampling errors included close/positive margins seen only on deeper PS and not present on FS slides, as well as close/positive margins that were not sampled at the time of FS (gross sampling error). Only one FN case was due to interpretation error. In this case in-situ carcinoma favored to be classic lobular carcinoma in-situ (LCIS) on FS was identified close to the margins and on PS was interpreted as pleomorphic LCIS, prompting reexcision. Of note, four FN cases did not require reexcision due to anatomic reasons (the close margin represented the limit of resection at the deep margin) and one patient with did not elect to undergo advised reoperation despite a final close margin.
Multivariable logistic regression revealed invasive lobular carcinoma subtype, tumor multifocality, and larger tumor size to be significantly associated with increased likelihood for reoperation (Table 2). Univariable analysis found that disease multifocality and larger tumor size were factors significantly associated with FN cases. Additionally, FN cases were also associated with lobular subtype and the presence of both mass and microcalcifications on mammography (Table 3).
There were 73 (40.3%) study and 94 (50%) control cases with multifocal disease, invasive lobular carcinoma, and/or largest tumor focus ≥ 2.0 cm. When any of these factors were present reoperation rates were higher but significantly reduced with FSM, from 75.5% to 43.8% in control and study groups, respectively (Figure 6).
Assessment of FP margins proved challenging in some cases as the foci would occasionally change between the FS and deeper, correlative PS slides (e.g. the foci became smaller or larger or would be closer or further away from the margin(s) than reported at the time of FS). Thus we felt that the criteria used to define a FP margin (outlined above) would best identify true FP cases. Using this definition there were only 6 cases with FP margins (6/189; 3.2%), 5 of which had one FP margin and one of which had two FP margins. In three of the cases the FP margins were likely due to over-interpretation in which there was biopsy site at the margin but no identifiable tumor close to the margin on re-reviewed FS or correlative PS slides. In the other three cases the FP margins were likely due to a combination of the focus changing upon deeper sectioning for PS and possible FS artifact (e.g. folding or fragmentation of adipose tissue) making the margin appear closer than it may have been. In all 6 cases additional breast tissue from these regions was excised with a mean volume of 25.5 cm3 (range 15.3–44 cm3).
Average turn-around-time (TAT) from receipt of specimen to final reporting of FS results was 23:48 minutes for all specimens and 26:48 minutes for lumpectomy specimens alone. TAT was directly proportional to number of blocks sampled, on average adding 2:09 minutes for each additional block submitted for FS. TAT was significantly increased when multiple specimens were submitted concurrently; however, this was directly related to increased FS block volume (Figure 7).
Intraoperative frozen section analysis of lumpectomy margins significantly decreases reoperation rates in patients undergoing BCT. In our series, the largest case-control study of its kind, there was nearly a three-fold decrease in reoperation rates following the implementation of our FSM practice. Reexcision rates were reduced from 48.9% to 14.9% in just the first year of practice. Similar results have also been observed by those who share a similar approach to ours; however, many of these studies are limited by lack of a comparable control group, small study size, differing definitions of close/positive margins, and lack of a clear outline of the technique utilized [26–30].
Different approaches for intraoperative evaluation have included cytologic methods, gross evaluation and FS analysis [26–40]. Bakhshandeh et al  and Ku et al  reported imprint cytology as a rapid and reliable method that offers high sensitivity in the detection of neoplasia. However, imprint cytology does not allow for the distinction between carcinoma in-situ and invasive carcinoma. Cytologic evaluation also has the significant limitation of only allowing interpretation of positive and not close margins which also require reexcision.
Gross evaluation is crucial in the examination of a lumpectomy specimen and guides sampling for microscopic assessment. However, gross evaluation is best at identifying the boundaries of easily identifiable solid masses. When fibrous septae extend from or surround a mass the distinction between neoplasia and benign breast tissue or biopsy site changes is less certain. When there is no clear mass but just fibrous tissue, calcifications, and/or biopsy site changes differentiation of neoplastic from benign tissue is impractical using gross evaluation alone. For example, Balch et al  identified 141/255 cases with grossly suspicious margins which prompted reexcision, ultimately resulting in a reexcision rate of 25%. However, 20% (51/255) had FN margins as compared to only 10.5% (19/181) FN cases in our study utilizing FSM.
The importance of lumpectomy gross evaluation should not be understated; however, the addition of FSM dramatically reduces rates of reexcision beyond what can be accomplished by gross examination alone. Camp et al  and Fukamachi et al  found that FS of shaved margins and FS of total cavity circumference excisions led to reductions in reexcision rates from 33.3% to 5.8% and 27% to 9.8%, respectively. Cabioglu et al  also used intraoperative gross examination not for margin assessment but rather as a guide for selective radiographic and FS analysis and found that this saved 29% of patients with invasive cancer and 9% of patients with DCIS from reexcision. Radiologic examination of the sliced gross specimen further reduced the reexcision rate to 22% in DCIS patients in a study by the same group .
Although effective at reducing reexcision, FS analysis on breast specimens has historically been controversial and many pathologists continue to worry that in challenging cases a FP FS result may prompt unnecessary resection of breast tissue. In our study the FP rate was low (only 3.2%) and resulted in excision of a relatively low volume of additional tissue (mean 25.5 cm3). Historically, FP in FS analysis posed a more significant risk as diagnostic excisional biopsies sent for FS diagnosis could result in conversion to mastectomy during the same procedure . However, today most breast lesions are amenable to preoperative histologic diagnosis, often attained via core biopsy which has high sensitivity and improved specificity when compared to FNA [42–44]. In our breast FS practice, FSM is only performed on patients undergoing BCT with a histologically-confirmed diagnosis of malignancy, greatly reducing uncertainty regarding the targeted lesion. Additionally, breast oncology surgeons at our institution generally will not convert to mastectomy during an attempt at BCT because of lack of patient preparedness. Instead, a best attempt at margin clearance is carried out while balancing the risks of poor cosmetic outcome and the likelihood of achieving negative final margins via intraoperative reexcision.
Perhaps the most limiting factor and the main reason why FS analysis on lumpectomy specimens is not routinely provided at most institutions are technical challenges in freezing breast tissue. Specifically, lumpectomy specimens with high adipose content do not adequately freeze or section using standard FS techniques, making microscopic measurements difficult to assess. We have found that liquid nitrogen provides lower temperatures that allow freezing and solidification of breast tissue and increased ease in sectioning for FS. In our experience, using just a minimal amount of OCT media for mounting tissue to the chuck was also crucial in attaining uniform tissue freezing and significantly reduced frozen section artifact seen with OCT-embedded tissue. These sections are easily interpretable as evidenced by the fact that we had only one pathologist interpretation error out of 181 cases.
We acknowledge that prior to implementation of this unique frozen section practice our institutional reoperation rates were near the high end of the published range, which varies widely due to such factors as varying institutional practices in selection of patients for BCT as well as varying definitions of close margins. We attribute our relatively high re-excision rate in part to being a referral center with increased willingness to attempt BCT in more complex cases. In addition, a previous study at our institution has shown that close margins (as defined above) result in residual disease in reexcision specimens comparable to positive margins . This has driven our relatively strict definitions of close margins as well as our strict practice of margin reexcision in patients with close margins. In fact, other studies with similar definitions of close margins report equivalent re-excision rates [2, 7, 11, 16, 20].
Despite a significant reduction in reoperation and reexcision with FSM there were still a number of patients who required additional procedure(s) to complete surgical therapy. Many of these patients, however, had risk factors known to be associated with an increased likelihood of margin positivity including tumor multifocality, lobular subtype, and larger tumor size [14, 15, 45–47]. Despite this, FSM was effective in reducing reoperation even when these features were present. Efforts at process improvement may further reduce reexcision and reoperation rates in these challenging cases; however, disease biology will likely still result in a continued number of patients who require multiple reexcisions and/or have failed attempt at BCT despite FSM. Preoperative evaluation will be important in identifying these patients for which BCT, even with the assistance of FSM, will be more difficult. This is supported by previous findings reported by Morrow et al  who observed that reexcision and conversion to mastectomy were highest for those patients who underwent BCT despite initial surgical recommendation to undergo mastectomy.
FS analysis does require greater resources and more OR time than evaluation via imprint cytology or gross evaluation only. Despite this, we have shown that FSM can be performed with very reasonable TAT. We have also observed that it does not significantly increase overall patient OR times and is cost-effective (in press) . With proper resources it is an easy adaptation as the technique is simple, easy to learn and perform, and utilizes materials that are typically already present within a frozen section laboratory.
Reoperation in patients undergoing BCT is also driven by the need to stage and treat metastatic axillary disease via SLNB and/or cALND. Until recently patients with macrometastatic (> 0.2 cm) and micrometastatic (> 0.2 mm but < 0.2 cm) positive SLNs would typically undergo cALND. However, recent evidence supports that many patients with limited micrometastases only, especially those with early stage breast cancer, may not derive clinical benefit from cALND [22– 25, 50]. In this study, new guidelines for cALND had not yet been adopted. Specifically, cALND was still being performed for micrometastatic disease in both study and control groups.
Despite this, only a few patients (4–5%) would have benefited from SLN FS analysis alone due to the additional need for reexcision of margins in the majority of patients with positive SLNs. Similarly, McLaughlin et al  identified only 6% of clinically node-negative patients (N = 1218) who would have avoided reoperation with SLN FS analysis alone. In both studies there is a selection bias toward patients who are more likely to lack axillary disease due to preoperative axillary staging. However, with changing surgical practices these numbers would be expected to be reduced even further.
In conclusion, reoperation rates will vary depending on patient population and patient and surgeon preferences regarding BCT. However, reexcision of margins is becoming increasingly important in dictating the need for reoperation in patients undergoing BCT. Surgeons tread a fine line between attaining negative margins and removing more tissue than necessary; therefore, reexcision rates will remain high without intraoperative evaluation. Our FSM practice is an example of a simple yet effective approach that has resulted in approximately two thirds of patients avoiding additional breast cancer surgery.
We would like to thank Christine Rigney, Tiffany Vail and Misty Wideman for their tireless effort in the development of this unique frozen section method and laboratory. We would also like to thank Debbie Laubach, Norah Naughton, Craig Newman and John Perrin for their administrative efforts in establishing the frozen section laboratory.
None of the above authors have any conflict of interest to disclose.
This paper was presented in part at the United States and Canadian Academy of Pathology (USCAP) Annual Meeting, San Antonio, TX, February 26 – March 4, 2011.
Julie M. Jorns, University of Michigan, Department of Pathology, 1500 East Medical Center Drive 2G332 UH, Ann Arbor, MI 48109, Email: ude.hcimu.dem@snrojj, Ph. (734) 936-6775, Fax # (734) 763-4095.
Daniel Visscher, Mayo Medical Laboratories, Department of Pathology.
Michael Sabel, University of Michigan, Department of Surgery.
Tara Breslin, University of Michigan, Department of Surgery.
Patrick Healy, University of Michigan, Department of Biostatistics.
Stephanie Daignaut, University of Michigan, Comprehensive Cancer Center, Biostatistics Core.
Jeffrey L. Myers, University of Michigan, Department of Pathology.
Angela Wu, University of Michigan, Department of Pathology.