Development of an intraoperative pathology consultation
service at a free-standing ambulatory surgical center:
clinical and economic impact for patients undergoing
breast cancer surgery
Michael S. Sabel, M.D.a,*, Julie M. Jorns, M.D.b, Angela Wu, M.D.b,
Jeffrey Myers, M.D.b, Lisa A. Newman, M.D., M.P.H.a, Tara M. Breslin, M.D., M.S.a
aDepartment of Surgery,bDepartment of Pathology, University of Michigan Comprehensive Cancer Center, 3304 Cancer
Center, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, USA
BACKGROUND: Second surgeries represent a significant detriment to breast cancer patients. We
examined the impact an intraoperative pathology consultation service had on multiple facets of breast
METHODS: We compared the 8 months before the establishment of a pathology laboratory, when
intraoperative pathology consultation was not available, with the 8 months subsequent, when it was
RESULTS: The average number of surgeries per patient decreased from 1.5 to 1.23, and the number
of patients requiring one surgery increased from 59% to 80%. Re-excisions decreased from 26% to 9%.
Frozen section allowed 93% of node-positive patients to avoid a second surgery for axillary lymph node
dissection. A cost analysis showed savings between $400 and $600 per breast cancer patient, even when
accounting for fewer axillary lymph node dissections based on the American College of Surgeons
Oncology Group Z0011 data.
CONCLUSIONS: Incorporation of routine intraoperative margin/sentinel lymph node assessment at
an outpatient breast surgery center is feasible, and results in significant clinical benefit to the patient.
Use of frozen section decreased both the time and cost required to treat patients.
© 2012 Elsevier Inc. All rights reserved.
Sentinel lymph node
Breast cancer surgery, including axillary lymph node
dissections (ALNDs) and mastectomies, are safely provided
on an ambulatory, outpatient basis, and increasingly are
being performed at free-standing surgical centers. Unfortu-
nately, as many as 40% to 60% of patients undergo second
or third procedures to achieve clear surgical margins with
breast conservation or complete a level I/II axillary dissec-
tion for positive sentinel nodes.1–5Additional procedures
are inconvenient for patients, and although important for
locoregional control, may result in increased morbidity
with respect to breast cosmesis, axillary symptoms, and
Intraoperative frozen section analysis of breast and sen-
tinel lymph node (SLN) specimens can decrease the need
* Corresponding author. Tel.: ?1-734-936-5827; fax: ?1-734-
E-mail address: email@example.com
Manuscript received December 14, 2010; revised manuscript July 18,
0002-9610/$ - see front matter © 2012 Elsevier Inc. All rights reserved.
The American Journal of Surgery (2012) 204, 66–77
for reoperation by allowing surgeons to resect additional
breast tissue and/or perform a completion axillary dissection
at the initial surgery.6,11,12Concerns regarding the labor-
intensive nature and technical challenges of preparing and
analyzing frozen breast tissue have led some to conclude
that intraoperative margin and SLN assessment should not
be performed. These are of greater concern at free-standing
surgical centers, often located at remote sites without an
on-site pathology laboratory or technical support for spec-
imen accessioning, processing, and intraoperative consulta-
tion that may be present at hospitals. As more breast surgi-
cal practices move to the ambulatory setting, innovations
will be required to provide state-of-the-art cancer care at
settings remote from main clinical hubs. This report de-
scribes the development of an intraoperative pathology con-
sultation service at a free-standing ambulatory surgical cen-
ter, and the impact this has had on patients, surgeons, and
the costs of health care delivery.
Initiation of a frozen section pathology
The breast surgical oncology service at the University of
Michigan transferred the bulk of its clinical activity from a
tertiary inpatient hospital to an ambulatory surgical center
4.5 miles away in March of 2009. Before and immediately
after this move, we did not perform intraoperative margin
and SLN frozen section analysis. A pathology laboratory
was designed and built within the operating room area
according to occupational safety and health administration
standards with specific attention to provision of accession-
ing stations, 2 grossing stations, ventilating hoods, a con-
ventional cryostat, staining station, and chemical, liquid
nitrogen, and specimen storage. Computer workstations and
a 3-head microscope were placed in an adjoining slide
review area. Full-time personnel included a pathology as-
sistant and a histotechnologist. Pathology faculty, a fellow,
and residents staffed the laboratory based on review of the
daily surgical schedule. Before establishment of the pathol-
ogy laboratory at the surgical center, all surgical specimens
were placed in formalin and transported to the main hospital
facility for accessioning, gross dissection, and processing.
Since initiation of the pathology service at the surgical
center, accessioning and gross dissection has been per-
formed on site for all specimens received from the operating
rooms and an adjacent medical procedures unit. Residual
tissues are stored in the laboratory, and tissue cassettes are
transported twice daily to the main hospital facility for
routine processing and final review through usual workflow
channels. Printed pathology reports contain the frozen sec-
tion results, results from review of fixed tissue, and results
from any additional immunohistochemical staining or fluo-
rescence in situ hybridization analysis.
Multidisciplinary breast cancer management
All newly diagnosed patients with biopsy-proven breast
cancer presenting to the University of Michigan Compre-
hensive Cancer Center are presented at a multidisciplinary
tumor board composed of surgical oncologists, medical
oncologists, radiation oncologists, radiologists, patholo-
gists, and associated support staff. Routine evaluation of all
patients with invasive cancer of 1.0 cm or greater includes
ultrasound imaging of the ipsilateral axillary basin, with
ultrasound-guided fine-needle aspiration (FNA) biopsy of
any abnormal-appearing lymph nodes. Patients treated with
neoadjuvant chemotherapy who have negative ultrasound
imaging or FNA biopsy undergo SLN biopsy before initi-
ating treatment. In addition, patients undergoing mastec-
tomy who are considering immediate reconstruction rou-
tinely are recommended to undergo SLN biopsy before
mastectomy to determine the possible need for postmastec-
tomy radiation therapy. Close surgical margins are defined
at the University of Michigan as 2 mm or less, for which
re-excision typically is recommended.
Breast conservation surgery margin evaluation by
The lumpectomy or re-excision lumpectomy specimen
along with corresponding mammographic films (if applica-
ble) are delivered to the frozen section laboratory. With the
aid of 3 orienting sutures, the specimen is oriented for the
pathology team. The margins of the specimen are inked
using 6 colors and sectioned at 2 to 3-mm intervals. After
gross examination of margin status by both the pathology
assistant and the pathologist, sections are taken for each
suspicious margin. The number of sections is highly driven
by gross examination findings; if the tumor grossly extends
close (?.5 cm) to a surgical margin, at least 2 to 3 radial
sections of the tumor to this margin is taken, if the tumor
extends to between .5 cm and 2.0 cm of a margin, at least
one radial section of this margin is taken, and if the distance
is greater than 2.0 cm from a margin, this margin is not
routinely sampled. More sections are taken in cases in
which the patient has undergone previous excisional biopsy/
lumpectomy, received prior chemotherapy, or had extensive
or exclusive ductal carcinoma in situ on prior biopsy be-
cause of the difficulty in grossly identifying residual carci-
noma. Each section is placed on a cryostat chuck with a very
small amount of optimal cutting temperature media and then
immersed in liquid nitrogen for 10 to 15 seconds. The chuck
is placed in a ?20°C cryostat and sprayed with additional
refrigerant. Sections 6- to 7-?m thick are cut on a ?20°C
cryostat, placed on plus slides, and stained with a rapid
hematoxylin and eosin technique, which takes around 30
seconds. At least 2 levels of each tissue block are evaluated.
Any margins in which invasive or in situ carcinoma extends
to within .2 cm are reported to the surgeon and re-excised.
Atypical ducts for which the differential includes atypical
67 M.S. Sabel et al.Intraoperative pathology in breast cancer
requires an initial investment from the institution, but the
eventual cost savings are realized primarily by the third-
party payers. The present reimbursement system does not
strongly incentivize the surgeon or the institution to initiate
this type of program, despite the tremendous benefit to the
patient. Therefore, a much more detailed cost analysis is
mandatory, along with a revised approach to reimbursement
to institutions providing this service.
In conclusion, establishment of an intraoperative pathol-
ogy consultation service at a free-standing ambulatory sur-
gical center is feasible, highly efficient, and has tremendous
benefits to patients and surgeons. It greatly decreases returns
to the OR, which not only spares patients the inconvenience
and anxiety of undergoing an additional surgical procedure,
but can decrease mastectomy rates and decrease the surgical
charges associated with breast cancer treatment. Even when
one accounts for potential changes in practice triggered by
the ACoSOG Z0011 trial, routine frozen section of the
margins and SLN remains time and cost efficient. Experi-
ments in clinical practice such as we describe requires
changes in both surgeon and pathologist work habits and
communication strategies that may conflict with long-stand-
ing habits and perceptions about priorities they must address
during the workday. It also imposes new and different rela-
tionships and/or interactions with personnel such as nurses and
pathology assistants, and potentially third-party payers. Meet-
of departmental and institutional leadership.
1. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the
lumpectomy surgical margin status in long-term results of breast con-
servation. Cancer 1995;76:259–67.
2. Waljee JF, Hu ES, Newman LA, et al. Predictors of re-excision among
women undergoing breast-conserving surgery for cancer. Ann Surg
3. Cellini C, Hollenbeck ST, Christos PJ, et al. Factors associated with
residual breast cancer after re-excision for close or positive margins.
Ann Surg Oncol 2004;11:915–20.
4. Sabel MS, Rogers K, Griffith K, et al. Residual disease after re-
excision lumpectomy for close margins. J Surg Oncol 2008;99:99–
5. Leong C, Boyages J, Jayasinghe UW, et al. Effect of margins on
ipsilateral breast tumor recurrence after breast conservation therapy for
lymph node-negative breast carcinoma. Cancer 2004;100:1823–32.
6. Olson TP, Harter J, Muñoz A, et al. Frozen section analysis for
intraoperative margin assessment during breast-conserving surgery
results in low rates of re-excision and local recurrence. Ann Surg
7. Lucci A, McCall LM, Beitsch PD, et al. Surgical complications asso-
ciated with sentinel lymph node dissection (SLND) plus axillary
lymph node dissection compared with SLND alone in the American
College of Surgeons Oncology Group Trial. J Clin Oncol 2007;25:
8. Husted Madsen A, Haugaard K, Soerensen J, et al. Arm morbidity
following sentinel lymph node biopsy or axillary lymph node dissec-
tion: a study from the Danish Breast Cancer Cooperative Group.
9. Waljee JF, Hu ES, Ubel PA, et al. Effect of esthetic outcome after
breast-conserving surgery on psychosocial functioning and quality of
life. J Clin Oncol 2008;26:3331–7.
10. Olson JA Jr, McCall LM, Beitsch P, et al. Impact of immediate versus
delayed axillary node dissection on surgical outcomes in breast cancer
patients with positive sentinel nodes: results from American College of
Surgeons Oncology Group Trials Z0010 and Z0011. J Clin Oncol
11. Weber S, Storm FK, Stitt J, et al. The role of frozen section analysis
of margins during breast conservation surgery. Cancer J Sci Am
12. Van Diest PJ, Torrenga H, Borgstein PJ, et al. Reliability of intraop-
erative frozen section and imprint cytological investigation of sentinel
lymph nodes in breast cancer. Histopathology 1999;35:14–8.
13. Lee MC, Rogers K, Griffith K, et al. Determinants of breast conser-
vation rates: reasons for mastectomy at a comprehensive cancer center.
Breast J 2009;15:34–40.
14. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no
axillary dissection in women with invasive breast cancer and sentinel
node metastasis: a randomized clinical trial. JAMA 2011;305:569–75.
15. Tafra L, Smith SJ, Woodward JE, et al. Pilot trial of cryoprobe-assisted
breast-conserving surgery for small ultrasound-visible cancers. Ann
Surg Oncol 2003;10:1018–24.
16. Ngô C, Pollet AG, Laperrelle J, et al. Intraoperative ultrasound local-
ization of nonpalpable breast cancers. Ann Surg Oncol 2007;14:
17. Rahusen FD, Bremers AJ, Fabry HF, et al. Ultrasound-guided lumpec-
tomy of nonpalpable breast cancer versus wire-guided resection: a
randomized clinical trial. Ann Surg Oncol 2002;9:994–8.
18. Moore MM, Whitney LA, Cerilli L, et al. Intraoperative ultrasound is
associated with clear lumpectomy margins for palpable infiltrating
ductal breast cancer. Ann Surg 2001;233:761–8.
19. Karni T, Pappo I, Sandbank J, et al. A device for real-time, intraop-
erative margin assessment in breast-conservation surgery. Am J Surg
20. Allweis TM, Kaufman Z, Lelcuk S, et al. A prospective, randomized,
controlled, multicenter study of a real-time intraoperative probe for
positive margin detection in breast-conserving surgery. Am J Surg
21. Cabioglu N, Hunt KK, Sahin AA, et al. Role for intraoperative margin
assessment in patients undergoing breast-conserving surgery. Ann
Surg Oncol 2007;14:1458–71.
22. Chagpar A, Yen T, Sahin A, et al. Intraoperative margin assessment
reduces reexcision rates in patients with ductal carcinoma in situ
treated with breast-conserving surgery. Am J Surg 2003;186:371–7.
23. Camp ER, McAuliffe PF, Gilroy JS, et al. Minimizing local recurrence
after breast conserving therapy using intraoperative shaved margins
to determine pathologic tumor clearance. J Am Coll Surg 2005;201:
24. Cendán JC, Coco D, Copeland EM. Accuracy of intraoperative frozen-
section analysis of breast cancer lumpectomy-bed margins. J Am Coll
25. Fukamachi K, Ishida T, Usami S, et al. Total-circumference intraop-
erative frozen section analysis reduces margin-positive rate in breast
conservation surgery. Jpn J Clin Oncol 2010;40:513–20.
26. Fleming FJ, Hill AD, Mc Dermott EW, et al. Intraoperative margin
assessment and re-excision rate in breast conserving surgery. Eur
J Surg Oncol 2004;30:233–7.
27. Noguchi M, Minami M, Earashi M, et al. Pathologic assessment of
surgical margins on frozen and permanent sections in breast conserv-
ing surgery. Breast Cancer 1995;2:27–33.
28. Sauter ER, Hoffman JP, Ottery FD, et al. Is frozen section analysis of
reexcision lumpectomy margins worthwhile? Margin analysis in breast
reexcisions. Cancer 1994;73:2607–12.
29. Dener C, Inan A, Sen M, et al. Intraoperative frozen section for mar-
gin assessment in breast conserving surgery. Scand J Surg 2009;98:
76 The American Journal of Surgery, Vol 204, No 1, July 2012
30. Klimberg VS, Westbrook KC, Korourian S. Use of touch preps for
diagnosis and evaluation of surgical margins in breast cancer. Ann
Surg Oncol 1998;5:220–6.
31. Cox CE, Pendas S, Ku NN, et al. Local recurrence of breast cancer after
cytological evaluation of lumpectomy margins. Am Surg 1998;64:533–7.
32. Cox CE, Hyacinthe M, Gonzalez RJ, et al. Cytologic evaluation of
lumpectomy margins in patients with ductal carcinoma in situ: clinical
outcome. Ann Surg Oncol 1997;4:644–9.
33. Creager AJ, Shaw JA, Young PR, et al. Intraoperative evaluation of
lumpectomy margins by imprint cytology with histologic correlation: a
community hospital experience. Arch Pathol Lab Med 2002;126:846–8.
34. D’Halluin F, Tas P, Rouquette S, et al. Intra-operative touch prepara-
tion cytology following lumpectomy for breast cancer: a series of 400
procedures. Breast 2009;18:248–53.
35. McLaughlin SA, Ochoa-Frongia LM, Patil SM, et al. Influence of
frozen-section analysis of sentinel lymph node and lumpectomy
margin status on reoperation rates in patients undergoing breast-
conservation therapy. J Am Coll Surg 2008;206:76–82.
36. Genta F, Zanon E, Camanni M, et al. Cost/accuracy ratio analysis in
breast cancer patients undergoing ultrasound-guided fine-needle aspi-
ration cytology, sentinel node biopsy, and frozen section of node.
World J Surg 2007;31:1155–63.
37. Fortunato L, Amini M, Farina M, et al. Intraoperative examination of
sentinel nodes in breast cancer: is the glass half full or half empty? Ann
Surg Oncol 2004;11:1005–10.
38. Jeruss JS, Hunt KK, Xing Y, et al. Is intraoperative touch imprint
cytology of sentinel lymph nodes in patients with breast cancer cost
effective? Cancer 2006;107:2328–36.
77 M.S. Sabel et al. Intraoperative pathology in breast cancer