Escolar Documentos
Profissional Documentos
Cultura Documentos
Abstract
This chapter aims to highlight the pros and cons of the use of a frozen
section (FS) in the diagnosis of ovarian pathology at the time of surgery.
Like all approaches, it is not perfect and does rely on a very close working
relationship between the pathologist and surgeon to ensure that when, and
if, it is used the maximum patient benefit is obtained. A FS (like all
diagnostic pathology) will never be fully accurate. However, if one accepts
its potential limitations, it can be a very good tool in the management of
patients with suspected ovarian pathology. This chapter will aim to
highlight major issues with the use of a FS service for ovarian diagnosis
and will outline potential pitfalls. It is not intended to be a textbook of FS
ovarian pathology the remainder of this book describes in far greater
detail the diagnostic criteria for ovarian pathology diagnosis. These still
apply even if based on FS material. A recent survey has shown that FS use
in the UK, when performed, is largely done for ovarian/pelvic masses and
lymph nodes in cervical cancer surgery.
Introduction
This chapter aims to highlight the pros and
cons of the use of a frozen section (FS) in the
diagnosis of ovarian pathology at the time of
surgery. Like all approaches, it is not perfect and
does rely on a very close working relationship
between the pathologist and surgeon to ensure
133
P.A. Cross
134
FS Booking/Transport
Given that nearly all cases of suspected malignancy will be discussed within the setting of an
MDT preoperatively, cases where a FS may be
of use can be identified. This allows the surgeons
to plan their operating lists and equally allows
them to prewarn the laboratory of the need for a
FS ideally at least 24 hours in advance. This
allows the laboratory to ensure sufficient staffing, including alerting the pathologist. How such
a planned FS is dealt with and rostered within
the laboratory will depend on each individual
laboratorys approach to how it works. It is vital
to ensure a reporting pathologist is identified.
Given that a FS will only involve up to 510 min
of a pathologists time (description/block taking/
reporting), this should not be overly disruptive to
the pathologists routine working pattern. Such
prior booking also ensures that all staff involved
with the specimen transfer (in particular portering staff and lab reception staff) are alerted in
advance.
If the FS is no longer required for any reason,
it should also be self-evident that the surgical
team should inform the laboratory so that they
can be stood down for that FS.
It is obvious that a reliable cryostat is essential
to the performance of a FS. Most laboratories
within the UK will have one, but it is often infrequently used. In the UK, FS use is not common,
135
Communication of Results
Whenever a FS is performed, clear, concise,
unambiguous communication is vital between
the requesting surgeon and reporting pathologist.
It should go without saying that the patient demographics on the request form and specimen pot
must be consistent with each other and easy to
read. The request form must state why the FS is
required and also any relevant clinical findings or
history. This should include operative findings,
but also any abnormal tumor markers. It must
also include any relevant medical history, and in
this context any previous history of malignancy is
essential. It is amazing how often such a history
appears to be forgotten about! Given the potential
for secondary malignancy presenting as an ovarian mass, any history of prior malignancy is vital
for the reporting pathologist. Such information
may allow the pathologist to suggest that any
malignancy may not be of ovarian origin and
P.A. Cross
136
Fig. 6.1 Gross view of intact simple serous cyst (a) and of smooth, internal lining (b)
137
Fig. 6.2 Gross view of simple mucinous cyst (a) and of multiloculated appearances on section (b)
FS Appearance/Artifacts
Because the FS tissue is not processed through
the usual histological process of dehydration/
rehydration, a FS has a different, albeit similar,
microscopic appearance to routinely processed
histological material. While the architecture is
essentially the same, the cellular detail is different, with larger nuclei and often more prominent
nucleoli i.e., less shrinkage artifact. Mitotic figures, whatever the nature of the lesion, are often
more apparent than on routine material.
Overinterpretation of what are routine FS changes
must be avoided, and comparison with any recognizable benign tissue within the section should be
taken to assess variation from the norm.
Avoidance of any necrotic/infarcted areas is
essential, as is overinterpretation of pyknosis/
karyorrhexis. Hopefully careful block selection
as outlined above will minimize this. There is
also often an apparent multilayering of simple
epithelium more so than is seen in routine
P.A. Cross
138
Table 6.1 Pooled typical literature values for sensitivity and specificity for ovarian FS diagnosis by report category
Medeiros et al.a
Heatleya
Geomni et al.a
Ilvan et al.b
Cross et al.b
Benign vs. BL
Sensitivity Specificity
(%)
(%)
99
66
98.9
70.8
100
86.8
99
72.3
BL vs. carcinoma
Sensitivity Specificity
(%)
(%)
91
95
93.6
93.1
100
88.9
98
83.5
PPV
NPV
LR+
LR
Benign vs.
carcinoma
97.9
(97.398.4)
99.5
(98.999.7)
23.99
(18.5231.1)
0.003
(0.010.006)
Benign vs.
BL
94.9
(94.195.7)
92.3
(8994.6)
3.384
(2.943.89)
0.015
(0.010.022)
BL vs.
carcinoma
77.7
(73.587.4)
98.2
(97.398.8)
13.293
(10.9416.15)
0.069
(0.0470.103)
139
P.A. Cross
140
Cross et al.
(11.6 % of all
FS diagnoses)
112
37
18
0
167
Ilvan et al.
(18.3 % of all
FS diagnoses)
71
13
27
2
113
Fig. 6.3 Frozen section appearance of benign endometriosis showing glands and stroma (a F 10), and at higher view
(b F 40), note the bland glands and stroma and intimate association of the two
141
Fig. 6.4 Simple follicular cyst (a FS 10, b FS 40). Note multilayering and variable nuclear size. An occasional
mitosis may also be seen. However, note the simple cyst architecture, and no invasion is present
P.A. Cross
142
Fig. 6.5 Simple serous cyst (a frozen section 40, b paraffin section 40). Note apparent multilayering on FS but lack
of other atypical features, confirmed on the PS
143
Fig. 6.7 Borderline serous lesion (a FS 10, b FS 40). Note architectural complexity and multilayering and nuclear
variability
morphism and mitotic activity, as well as some psammoma bodies in (c). PS of final histology from same block
(d, 40)
quent mitotic figures are present, then a borderline or frankly malignant diagnosis should be
considered, but such malignant urothelial lesions
are relatively rare.
P.A. Cross
144
Fig. 6.9 Simple mucinous cyst. (a) (FS 20) and (b) (FS 40) show bland mostly enteric glands, with no atypical
cellular features although some complexity of the actual cyst lining is not unusual
Fig. 6.10 Borderline mucinous cyst (all FS, a 10, b 10, c 40) showing marked atypia and complexity, but with no
invasion seen
145
Fig. 6.11 FS of metastatic colonic adenocarcinoma (a 10, b 40). Note high-grade nuclear features and typical (when
present) dirty-type necrosis
P.A. Cross
146
Pediatric Ovarian FS
The range and type of possible ovarian pathology, both benign and malignant, are very different in the pediatric age range. No tumor has an
absolute age predilection, but one must consider
a potentially different range of tumors in the
young. However, the approach to surgery is typically far more conservative in children, and diagnosis will usually rest on routinely processed
material rather than on a FS diagnosis. As such, a
routine FS approach to pediatric pathology in
general appears more limited, which is supported
147
Fig. 6.15 Monodermal teratoma struma ovarii (FS, a 10 and b 40). Note well-defined follicles with mostly single
cell layers, with plentiful eosinophilic material (colloid)
Fig. 6.16 Metastatic lobular carcinoma to ovary (a FS 40, b PS 40). Note typical lobular Indian file arrangement and
occasional intracytoplasmic lumen in some cells
148
References
1. Ganesan R, Brown LJR, Kehoe S, McCluggage WG,
El-Bahrawy MA. The role of frozen sections in gynaecological oncology: survey of practice in the United
Kingdom. Eur J Obstet Gynecol Reprod Biol.
2013;166:2048.
2. NICE. Ovarian cancer: the recognition and initial
management of ovarian cancer. Issued Apr 2011.
http://publications.nice.org.uk/ovarian-cancer-cg122
3. Naik R, Cross P, Lopes A, Godfrey K, Hatem MH.
True versus apparent stage 1 epithelial ovarian
cancer: value of frozen section analysis. Int J Gynecol
Cancer. 2006;16 Suppl 1:416.
4. Dunn BE, Choi H, Recla DL, Kerr SE, Wagenman
BL. Robotic surgical pathology between the Iron
Mountain and Milwaukee Department of Veretans
Affairs Medical Centre: a 12 year experience. Hum
Pathol. 2009;40(8):10929.
5. Ilvan S, Ramazanoglu R, Akyildiz U, Caley Z, Bese
T, Oruc N. The accuracy of frozen section (intraoperative consultation) in the diagnosis of ovarian masses.
Gynecol Oncol. 2005;97(2):3959.
6. Geomini P, Bremer G, Kruitwagen R, Mol
BW. Diagnostic accuracy of frozen section diagnosis
of the adnexal mass: a meta analysis. Gynecol Oncol.
2005;96(1):19.
7. Kim JW, Kim TJ, Park YG, Lee HS, Lee CW, Song
MJ, Lee KH, Hur SY, Bae SN, Park JS. Clinical analysis of intra-operative frozen section proven borderline tumors of the ovary. J Gynecol Oncol.
2009;20(3):17680.
8. Gultekin E, Gultekin OE, Cingillioglu B, Sayhan S,
Sanci M, Yildirim Y. The value of frozen section evaluation in the management of borderline ovarian
tumors. J Cancer Res Ther. 2011;7:41620.
9. Twigg J, Cruickshank D. Intra-operative frozen section analysis for suspected early stage ovarian cancer.
BJOG. 2012;119(7):896.
10. Baker P, Oliva E. A practical approach to intraoperative consultation in gynecological pathology. Int J
Gynecol Pathol. 2008;27:35365.
11. Novis DA, Zarbo RJ. Institutional comparison of frozen section turnaround time. Arch Pathol Lab Med.
1997;121:55967.
12. Cross PA, Naik R, Patel A, Nayar AGN, Hemming
JD, et al. Intra-operative frozen section analysis for
suspected early stage ovarian cancer: 11 years of
Gateshead Cancer Centre experience. BJOG.
2012;119(2):194201.
P.A. Cross
13. NHS Diagnostics Improvement. http://www.improvement.nhs.uk/diagnostics/
14. RCPath. Datasets for the histopathological reporting
of neoplasms of the ovaries and fallopian tubes and
primary carcinomas of the peritoneum. 3rd ed. Issued
Nov 2010. http://www.rcpath.org/publications-media/
publications/datasets/datasets-for-thehistopathological-reporting-of-neoplasms-of-theovaries-and-fallopian-tubes-and-pri.htm
15. Heatley MK. A systematic review of papers examining the use of intraoperative frozen section in predicting the final diagnosis of ovarian lesions. Int J Gynecol
Pathol. 2012;31:1115.
16. Medeiros LR, Rosa DD, Edelweiss MI, Stein AT,
Bozzetti MC, Zelmanowicz A, Pohlmann PR, Meurer L,
Carballo MT. Accuracy of frozen section analysis in the
diagnosis of ovarian tumours: a systematic quantitative
review. Int J Gynecol Cancer. 2005;15(2):192202.
17. Kim K, Chung HH, Kim JW, Park NH, Song YS,
Kang SB. Clinical impact of under-diagnosis by frozen
section examination is minimal in borderline ovarian
tumours. Eur J Surg Oncol. 2009;35(9):96973.
18. Storms AA, Sukumvanich P, Monaco SE, Beriwal S,
Krivak TC, Olawaiye AB, Kanbour-Shakir A. Mucinous
tumors of the ovary: diagnostic challenges and clinical
implications. Gynecol Oncol. 2012;125:759.
19. Soslow RA. Histologic subtypes of ovarian carcinoma: an overview. Int J Gynecol Pathol. 2008;27(2):
16174.
20. Pongsuvareeyakul T, Khunamornpong S, Settakorn J,
Sukpan K, Suprasert P, Siriaunkgul S. Accuracy of
frozen section diagnosis of ovarian mucinous tumours.
Int J Gynecol Cancer. 2012;22:4006.
21. Puls I, Heidtman E, Hunter JE, Crane M, Stafford
J. The accuracy of frozen section by tumour weight
for ovarian epithelial neoplasms. Gynecol Oncol.
1997;67(1):169.
22. Seidman JD, Kurman RJ, Ronnett BM. Primary and
metastatic mucinous adenocarcinomas in the ovaries.
Incidence in routine practice with a new approach to
intra-operative diagnosis. Am J Surg Pathol.
2003;27:98593.
23. Yemelyanova AV, Vang R, Judson K, Wu LS, Ronnett
BM. Distinction of primary and metastatic mucinous
tumours involving the ovary: analysis of size and laterality data by primary site with re-evaluation of an
algorithm for tumour classification. Am J Surg Pathol.
2008;32(1):12838.
24. Stewart CJ, Brennan BA, Hammond IG, Leung YC,
McCartney AJ. Accuracy of frozen section in distinguishing primary ovarian neoplasia from tumours
metastatic to the ovary. Int J Gynecol Pathol.
2005;24(4):35662.
25. Stewart CJ, Brennan BA, Hammond IG, Leung YC,
McCartney AJ, Ruba S. Intraoperative assessment of
clear cell carcinoma of the ovary. Int J Gynecol
Pathol. 2008;27:47582.
26. Preston HS, Bale PM. Rapid frozen section in
paediatric pathology. Am J Surg Pathol. 1985;9(8):
5706.