International Journal of Gynecological Pathology

38:S9–S24, Lippincott Williams & Wilkins, Baltimore

Copyright © 2018 International Society of Gynecological Pathologists. Published by Wolters Kluwer Health, Inc.
on behalf of the International Society of Gynecological Pathologists.

Endometrial Carcinoma, Grossing and Processing Issues:

Recommendations of the International Society of Gynecologic
Pathologists

Anais Malpica, M.D., Elizabeth D. Euscher, M.D., Jonathan L. Hecht, M.D., Ph.D.,
Rouba Ali-Fehmi, M.D., Charles M. Quick, M.D., Naveena Singh, F.R.C.Path.,
Lars-Christian Horn, M.D., Ph.D., Isabel Alvarado-Cabrero, M.D., Ph.D.,
Xavier Matias-Guiu, M.D., Ph.D., Lynn Hirschowitz, F.R.C.Path., Máire Duggan, M.D.,
Jaume Ordi, M.D., Vinita Parkash, M.D., Yoshiki Mikami, M.D., Ph.D., M. Ruhul Quddus, M.D.,
Richard Zaino, M.D., Annette Staebler, M.D., Charles Zaloudek, M.D.,
W. Glenn McCluggage, F.R.C.Path., and Esther Oliva, M.D.

Summary: Endometrial cancer is the most common gynecologic neoplasm in developed

countries; however, updated universal guidelines are currently not available to handle
specimens obtained during the surgical treatment of patients affected by this disease. This
article presents recommendations on how to gross and submit sections for microscopic
examination of hysterectomy specimens and other tissues removed during the surgical
management of endometrial cancer such as salpingo-oophorectomy, omentectomy, and
lymph node dissection—including sentinel lymph nodes. In addition, the intraoperative
assessment of some of these specimens is addressed. These recommendations are based
on a review of the literature, grossing manuals from various institutions, and a
collaborative effort by a subgroup of the Endometrial Cancer Task Force of the
International Society of Gynecological Pathologists. The aim of these recommendations

From the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (A.M., E.D.E.); Department of
Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School (J.L.H.); Department of Pathology, Massachusetts General
Hospital and Harvard Medical School (E.O.), Boston, Massachusetts; Department of Pathology, Wayne State University, Detroit, Michigan
(R.A.F.); Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.M.Q.); Department of Cellular
Pathology, Barts Health NHS Trust, London (N.S.); Department of Cellular Pathology, Birmingham Women’s NHS Trust, Birmingham
(L.H.), UK; Division of Gynecologic, Breast and Perinatal Pathology, University Hospital, Leipzig (L.C.H.); Institute of Pathology, University
Hospital of Tübingen, Tübingen (A.S.), Germany; Department of Pathology, Hospital de Oncología Siglo XXI, Mexico City, Mexico City,
Mexico (I.A.C.); Department of Pathology, Hospital Universitari de Bellvitge and Hospital Universitari de Arnau de Vilanova, Idibell,
Irblleida, and Universitat de Lleida, Ciberonc (X.M.G.); Department of Pathology, Hospital Clinic of Barcelona, Universitat de Barcelona,
Barcelona (J.O.), Spain; Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Alberta,
Canada (M.D.); Department of Pathology, Yale University School of Medicine, New Haven, Connecticut (V.P.); Department of Diagnostic
Pathology, Kumamoto University Hospital, Kumamoto, Japan (Y.M.); Department of Pathology, Women and Infants Hospital and The
Warren Alpert Medical School of Brown University, Providence, Rhode Island (M.R.Q.); Division of Anatomic Pathology, Hershey Medical
Center, Pennsylvania State University, Hershey, Pennsylvania (R.Z.); Department of Pathology, University of California, San Francisco, San
Francisco, California (C.Z.); and Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK (W.G.M.).
Presented in part at the International Society of Gynecological Pathology Companion Meeting, 106th United States and Canadian Academy
of Pathology Meeting, March 2017, San Antonio, TX.
The authors declare no conflict of interest.
Address correspondence and reprint requests to Anais Malpica, MD, Department of Pathology, The University of Texas MD Anderson
Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77098. E-mail: amalpica@mdanderson.org.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

S9 DOI: 10.1097/PGP.0000000000000552
S10 A. MALPICA ET AL.

is to standardize the processing of endometrial cancer specimens which is vital

for adequate pathological reporting and will ultimately improve our understanding of
this disease. Key Words: Endometrial carcinoma—Gross examination—Macroscopic
examination—Processing—Pathology—Tumor size—Staging—Lymph nodes—Sentinel
lymph nodes.

Endometrial cancer is the sixth most common will assist in standardizing the processing of these
malignant neoplasm in women worldwide and is the specimens, which is critical not only for an accurate
most common gynecologic malignancy in developed pathology report, but also to improve our knowledge of
countries (1). In the United States, the American this disease.
Cancer Society estimates ∼63,230 new cases of
endometrial cancer and 11,350 deaths due to this
disease in 2018 (2). Although no updated universal RECOMMENDATIONS
guidelines are currently available on how to gross the General
surgical specimens obtained in cases of endometrial All pathology reports should include a detailed section
cancer, it is widely accepted that a thorough gross/ code/block key on which the origin/designation of all
macroscopic examination will optimize the acquisition tissue blocks should be recorded. This information is
of information required for proper diagnosis, staging, particularly important should there be a need for internal
treatment, and prognosis. This article presents the or external review as reviewers need to be clear about the
recommendations to handle and gross such specimens origin of each tissue block in order to provide an
as proposed by the members of the Endometrial Cancer informed specialist opinion. Recording the origin/desig-
Task Force of the International Society of Gyneco- nation of all tissue blocks also facilitates retrieval of
logical Pathologists. These recommendations cover not blocks for immunohistochemical or molecular analysis,
only hysterectomy specimens, including those obtained research studies or clinical trials.
prophylactically in patients at risk of developing this
disease, but also salpingo-oophorectomy and omentec-
tomy specimens, as well as sentinel and non–sentinel
HYSTERECTOMY SPECIMEN HANDLING
lymph nodes (SLN). This work is based on a review of
the literature, grossing manuals from various institu- General Rule of Gross/Macroscopic Examination
tions, and a collaborative effort by a subgroup of the Orient the specimen, that is identify the anterior and
above-mentioned task force. These recommendations posterior walls of the uterus using anatomic landmarks

FIG. 1. Orientation of hysterectomy specimen using anatomical landmarks, peritoneal reflection is higher anteriorly (arrow) and the sequence
of structures in the adnexal region is round ligament (*), fallopian tube (arrowhead) and ovary (**) (A), peritoneal reflection is lower posteriorly
(arrow) and the sequence of structures in the adnexal region is ovary (**), fallopian tube (arrowhead) and round ligament (B), the latter is not
visualized in this photograph.

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 ENDOMETRIAL CARCINOMA, GROSSING AND PROCESSING S11

such as the peritoneal reflection and the round ligament/ Serosal inking can aid in specimen orientation and in
ovaries (Figs. 1A, B). Document all organs/structures confirming the presence of tumor at the uterine serosal
received and record their measurements and gross surface if present (Figs. 2A, B). In addition, inking the
appearance. peritoneal and nonperitoneal surfaces and extending the
ink all the way to the ectocervical/vaginal cuff margin in
cases where the tumor has invaded the cervical stroma is
WHEN SHOULD THE UTERUS BE OPENED?
useful to provide an accurate measurement of the depth
Recommendation of cervical stromal invasion relative to the full thickness
Uteri should be opened immediately upon receipt in of the cervical wall and the status of the ectocervical/
the pathology laboratory and placed in formalin vaginal cuff margin (Figs. 2C, D). Of note, measurement
within an hour of opening whenever possible. of the depth of cervical stromal invasion and its
The purpose of opening the uterus immediately is to relationship with the full thickness of the cervical wall
prevent autolysis, which is very common in hysterec- are not included in the College of American Pathologists
tomy specimens, and to avoid potential preanalytical (CAP) protocol for endometrial cancer (11), but they are
issues when ordering immunohistochemical or molec- often required by radiation oncologists to delineate
ular studies (3–5). Although most of the grossing treatment recommendations (12). The practice of
manuals used in academic institutions in North inking is variably addressed in the multiple grossing
America do not provide specific timelines, some include manuals reviewed. Some manuals do not mention it at
specific instructions such as opening and fixation within all while others recommend inking as follows: (1)
1 h of receipt in the pathology laboratory, documenta- serosal/nonserosal surfaces for orientation purposes, (2)
tion of cold ischemic interval and interval in formalin, inking serosal abnormalities only to confirm tumor at
and prompt procurement of fresh tissue for banking the serosal surface, and (3) inking only of the
and/or investigational protocol purposes (6). parametrium and vaginal cuff if present. Overall,
inking is helpful, but it is important to blot the inked
SHOULD THE PATHOLOGY PERSONNEL surfaces right after applying the ink to avoid ink
displacement and the potential misinterpretation of
MANAGE REQUESTS FOR FRESH TISSUE this finding.
FOR STUDIES?
Recommendation SHOULD THE UTERINE WEIGHT BE
The pathology laboratory personnel and/or pathol-
ogists should manage the requests for fresh tissue for INCLUDED IN THE REPORT?
banking and/or investigational protocols and this task Recommendation
should be completed as soon as the specimen is The need to include the uterine weight in the
received in the pathology laboratory. pathology report is geographically dependent. This
Procurement of fresh tissue for banking or research parameter has to be provided in the United States
protocols should be done as soon as possible as prolonged because the Current Procedural Terminology (CPT)
ischemia affects tissue quality for investigational purposes. code required for reimbursement purposes changes
Tissue procurement for research should not compromise according to a uterine weight of 250 g (i.e. CPT code
pathologic evaluation (6–10). Therefore, a pathologist 58570 is used for a uterus with a weight of ≤ 250 g
should be consulted in questionable cases. In addition, the while CPT code 58572 is used for the same specimen if
tissue procured for research should be available for the uterus weighs > 250 g) (13–15).
diagnostic purposes if needed. Although uterine weight could be related to surgical
outcome as larger uteri may be associated with increased
SHOULD THE PERITONEAL AND/OR NON- duration of surgery or risks of surgical complications
(16–18), the main reason to include uterine weight in the
PERITONEAL SURFACES BE INKED?
pathology report is to ensure proper reimbursement for
Recommendation the procedure when this is performed in the United
Inking of peritoneal and/or nonperitoneal surfaces States. In addition, this information is also required for
is recommended in hysterectomy specimens and is the case list submitted by candidates applying to
mandatory in radical hysterectomy specimens in certification by the American Board of Obstetrics and
which parametrium and vaginal cuff are present. Gynecology in the United States (19).

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S12 A. MALPICA ET AL.

FIG. 2. Inking the anterior and posterior uterine serosal surfaces with extension of the ink to the ectocervix or vaginal cuff margin (A), helps to
confirm the presence of tumor in the uterine serosa (arrow) (B), and in cases with cervical stromal involvement (C) the measurement of the
relationship of the stromal invasion to the full thickness of the cervical wall (line), and the proper identification of the ectocervical or vaginal
cuff margin (*) (D).

HOW SHOULD THE UTERUS BE OPENED? neoplasm is often considered “best practice” and
represents standard pathology practice.
Recommendation
Currently, there is some controversy with regards to the
The uterus should be opened along the lateral
impact of tumor size on patient outcome; nevertheless,
uterine walls (3 and 9 o’clock).
tumors exceeding various established thresholds have been
The above method provides maximum exposure of the
associated with increased stage of disease and/or risk of
endometrial surface in a flat plane which allows better
recurrence (20–27). Therefore, at a minimum, the largest
visualization and measurement of the tumor (Fig. 3A).
dimension of the tumor should be reported (Figs. 4A, B).
Of note, the lateral uterine walls contain the cornua and
The other dimensions can be recorded, but are not
the pathologist should be aware that tumor involving the
required. Some manuals specify the need to record the 3
lumen of the proximal portion of the fallopian tube can
dimensions of a tumor; however, this is not a uniform
be interpreted as myoinvasive carcinoma (Figs. 3B, C).
approach as requirements for measurements are
All grossing manuals examined for this review, in which
not specifically outlined in several of the manuals
this procedure is described, recommend opening the
reviewed while others require 2 or only 1 tumor
uterus along the lateral walls (6).
dimension (6). The Royal College of Pathologists
Dataset for Histopathological Reporting of Endometrial
SHOULD THE TUMOR ALWAYS BE Cancer in the United Kingdom (28) recommends only
recording the maximum tumor dimension while the
MEASURED IN 3 DIMENSIONS?
current CAP checklist includes only the maximum
Recommendation tumor dimension as an optional element which is not
At least the largest dimension of the tumor must be required for accreditation (11). Another important
provided, although providing 3 dimensions of a issue regarding tumor size is that this parameter has a

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 ENDOMETRIAL CARCINOMA, GROSSING AND PROCESSING S13

FIG. 3. Opening the uterus at 3 and 9 o’clock provides a maximum exposure of the endometrial surface in a flat plane to better visualize and
measure an endometrial tumor (A), the cornua can contain tumor (B) and this should not be mistaken for myometrial invasion (C).

pivotal role in one of the algorithms used to triage cular invasion are included in multivariate analysis
patients intraoperatively for lymph node dissection in (23,24); (2) some studies have demonstrated an
the setting of low-risk endometrial carcinoma. The association between tumor size, either ≥ 3.5 or > 5
so-called “Mayo algorithm” is based on an association cm, and recurrence risk and/or prognosis in otherwise
between tumor size and risk of lymph node meta- low-risk cancers (25,26); (3) other studies have not
stases (21,22). According to this algorithm, patients shown an association between tumor size and prognosis
with endometrioid adenocarcinoma, FIGO grades 1 or 2, (24,27).
measuring ≤ 2 cm and with ≤ 50% myometrial invasion
are spared of pelvic lymph node dissection as the risk of
HOW SHOULD THE UTERUS BE SECTIONED
lymph node metastases is <0.3% while patients with
similar tumors measuring > 2 cm and ≤ 50% myometrial (HORIZONTAL/TRANSVERSE
invasion undergo a dissection of pelvic lymph nodes as
OR LONGITUDINALLY)?
the risk of pelvic lymph node metastases increases to
10% (21). Recommendation
The controversy between tumor size and disease Horizontal/transverse sectioning is recommended.
outcome can be summarized as follows: (1) some All manuals reviewed, except one, suggest the use of
studies have shown an association between tumor size horizontal/transverse sectioning (left to right) from the
and risk of lymph node metastases, but tumor size has lower uterine segment to the fundus. However, vertical
not been found to be an independent predictive factor sectioning is advisable to demonstrate the lower uterine
when depth of myometrial invasion and lymphovas- segment in conjunction with upper cervix (6) (Fig. 5).

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S14 A. MALPICA ET AL.

FIG. 4. Measurement of endometrial carcinoma, small polypoid tumor (A), a tumor that involves the anterior and posterior walls in a
continuum, carpet-like fashion should be measured accordingly (B).

SHOULD THE TUMOR BE SUBMITTED tumor dimension (6). Also, a proposal for submitting at
ENTIRELY FOR HISTOLOGIC EXAMINATION? least 4 blocks of tumor has been presented (28). Of note,
IF NOT, HOW SHOULD THE NUMBER OF there are no data explicitly addressing the value of
SECTIONS BE DETERMINED? extensive histologic examination of an endometrial
carcinoma. Although the risk of missing a high-grade
Recommendation
(serous, clear cell, undifferentiated or neuroendocrine)
It is not necessary to submit an endometrial tumor
carcinoma component in association with an endome-
in its entirety for microscopic examination. Sampling
trioid carcinoma exists, these cases are uncommon (29).
one section per centimeter of the largest tumor dimension
(as is done with tumors at other anatomic sites) will
suffice. HOW MANY SECTIONS DO YOU TAKE IF
Grossing manuals provide a wide range of recom- YOU DO NOT SEE CARCINOMA ON GROSS
mendations; however, none advocates submitting the EXAMINATION, IF THERE IS A HISTORY OF
entire tumor unless it measures ≤ 3 cm. Several ATYPICAL ENDOMETRIAL HYPERPLASIA/
manuals advocate one section per centimeter of largest ENDOMETRIOID INTRAEPITHELIAL
NEOPLASIA (EIN) OR IF UNSUSPECTED
ATYPICAL ENDOMETRIAL HYPERPLASIA/
EIN OR ENDOMETRIAL CARCINOMA IS
DETECTED IN THE REPRESENTATIVE
SECTIONS OF A HYSTERECTOMY OBTAINED
FOR OTHER REASONS?
Recommendation
The entire endometrium and adjacent inner my-
ometrium should be submitted for microscopic
examination in the setting of a preoperative endome-
trial sampling demonstrating malignancy and no
visible lesion on gross examination or if there is a
history of atypical endometrial hyperplasia/EIN. The
same applies to hysterectomy specimens that have
been obtained for other reasons (leiomyomas, adeno-
myosis, etc.) with no gross endometrial lesion and
FIG. 5. Cross-sections of the uterine wall at the level of the corpus
(top arrow), longitudinal sections at the level of the lower uterine endometrial carcinoma or atypical endometrial hyper-
segment (middle arrow) and cervix (bottom arrow). plasia EIN detected on microscopic examination of

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 ENDOMETRIAL CARCINOMA, GROSSING AND PROCESSING S15

the initial representative sections. Sections of residual a relatively thin wall which allows the submission
myometrium should be placed in sequential order, of a full thickness section in a single cassette, it is
either in folded paper towels or gauze, in a formalin possible to submit all sections containing tumor as
filled container in case that the examination of full thickness sections.
additional myometrial tissue is needed to determine The manuals reviewed offered a wide range of
an accurate depth of myometrial invasion if any. recommendations, from at least one full thickness
In addition, cornual blocks need to be submitted in section to all submitted sections containing tumor to
cases of biopsy proven carcinoma, but no gross be of full thickness (6,28). In ideal circumstances, a
endometrial tumor. single full thickness section submitted after a careful
Most reviewed manuals recommend submitting the gross examination would be sufficient to determine the
entire endometrium when a preoperative diagnosis of deepest point of myometrial invasion (Fig. 6). However,
malignancy has been rendered and no gross lesion is myometrial invasion assessment may be complicated in
seen in the hysterectomy, or in cases of atypical certain circumstances such as cases with adenomyosis
endometrial hyperplasia/EIN (6). In addition, the involved by carcinoma, cases with peculiar patterns of
Royal College of Pathologists of the United Kingdom myometrial invasion like “adenoma malignum-like,”
recommends the submission of cornual blocks in cases “single cells,” “microcystic, elongated, and fragmented”
of biopsy proven carcinoma, but no visible endome- (31) or if an underlying leiomyoma is present distorting
trial tumor on gross examination (28). Of interest, the the uterine wall architecture. It should be noted that the
intraoperative evaluation of 1 random full thickness examination of the myometrium is important not only
section of the uterine wall from hysterectomies for assessment of depth of tumor invasion, but also to
obtained for endometrial carcinoma and no gross identify the unusual infiltrative patterns mentioned
lesion demonstrated the presence of microscopic above and to identify and quantify lymphovascular
tumor only in 3 (15%) of 20 cases with a final invasion. Regarding the assessment of the deepest
diagnosis of cancer (30). myometrial invasion in frozen section, several studies
have examined this issue and the number of sections
HOW MANY SECTIONS SHOULD INCLUDE used has ranged from 1 to 5 (32–37). Depth of
THE FULL THICKNESS OF THE MYOME- myometrial invasion is an independent predictor of
TRIUM TO DETERMINE THE MAXIMUM both lymph node metastases and prognosis (38) and
DEPTH OF INVASION? is part of the FIGO staging system (39). In cases
where the gross examination does not allow the
Recommendation submission of the deepest point of invasion with
At least, one full thickness section of the uterine confidence or in problematic cases such as those
wall—including serosa, is required to show the above, processing several full thickness sections of
deepest point of myometrial invasion. In uteri with the uterine wall may be necessary in order to render
an accurate assessment.

IF ADENOMYOSIS IS SUSPECTED, HOW

MANY SECTIONS SHOULD SAMPLE THE
FULL THICKNESS OF THE MYOMETRIUM TO
DETERMINE THE MAXIMUM DEPTH OF
INVASION?
Recommendation
The number of sections submitted should not be
altered in the context of adenomyosis. However, in
cases where the assessment of myometrial invasion is
difficult because of tumor involving adenomyosis
taking additional sections of the uterine wall may be
useful.
None of the manuals reviewed addresses the
FIG. 6. Cross-section of the uterine wall demonstrating deepest measurement of myometrial invasion in the context
point of myometrial invasion on gross examination (arrowhead). of adenomyosis (6).

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S16 A. MALPICA ET AL.

SHOULD THE TUMOR/NONTUMOR INTER- experience is accumulated to support or modify this

FACE BE SAMPLED? practice (40,43,44).
Women with Lynch syndrome are at increased risk of
Recommendation
malignancies, with colorectal, endometrial and ovarian
Whenever possible, the tumor/nontumor interface
cancer being the most frequent (45–48). Endometrial
should be submitted for microscopic examination.
cancer is the most common extracolonic tumor in these
This facilitates the measurement of the depth of
patients (47,49). Endometrial cancer cumulative incidence
myometrial invasion and the identification of pre-
at 70 years is consistently high for patients with MLH1
cursor lesions.
(34%), MSH2 (51%), MSH6 (49%), and PMS2 (24%)
Some of the manuals reviewed specifically indicate
germline mutations, and is frequently the first malignancy
the need to sample the tumor/nontumor interface (6).
diagnosed in women with Lynch syndrome (50). Ovarian
cancer is the second most common extracolonic neoplasia
HOW MUCH NON-NEOPLASTIC ENDOME- in women with Lynch syndrome with a cumulative
TRIUM SHOULD BE SUBMITTED? lifetime risk ranging from 6% to 14% (51–56). Prophy-
lactic hysterectomy and bilateral salpingo-oophorectomy
Recommendation
has been advocated as a cost-effective measure that
At least one representative section of non-neoplastic
significantly reduces the risk of gynecologic cancer in
endometrium should be submitted for microscopic
Lynch syndrome patients. This procedure is currently
examination. In addition, any grossly identified endome-
included in the National Comprehensive Cancer Network
trial lesions separate from the tumor should be submitted.
(NCCN) guidelines for the management of patients with
There is no universal recommendation about the
Lynch syndrome who are either postmenopausal or who
number of sections of grossly unremarkable endome-
have completed childbearing (41,57–61). The implemen-
trium to be submitted. Some manuals recommend
tation of this procedure has been increasing progressively
submitting one or 2 full thickness sections of uninvolved
(41,62). Endometrial findings in prophylactic hysterec-
endomyometrium (6).
tomy specimens in these patients include atypical hyper-
plasia and small and low grade endometrioid carcinomas
HOW MANY SECTIONS OF ENDOMETRIUM
(40,43,44,63). The finding of small incidental endometrial
AND ADNEXAL STRUCTURES SHOULD BE
carcinomas in these specimens emphasizes the need to
TAKEN IF THE PATIENT IS KNOWN TO HAVE
submit the entire endometrium for microscopic examina-
LYNCH SYNDROME?
tion (40,43,44,63). Regarding the need to submit in toto
Recommendation unremarkable fallopian tubes and ovaries for microscopic
All gross endometrial abnormalities need to be examination, using the SEE-FIM (Sectioning and Exten-
submitted for microscopic examination. In the absence sively Examining the FIMbriated End) protocol, there is
of a gross lesion, the endometrium should be submitted no current evidence to support this practice (40,43,44,63);
in toto. Macroscopic examination and sampling should however, as experience with these prophylactic specimens
be performed after fixation, in an orderly manner, is still limited, we recommend submitting unremarkable
for example sequentially from superior to inferior or adnexal structures entirely for microscopic examination as
vice versa. Sections should include the endomyometrial it has been proposed by a group of investigators (43).
interface. The lower uterine segment should be sub-
mitted in toto with longitudinal sections including the
HOW MANY SECTIONS OF THE LOWER
endocervical junction. Unremarkable ovaries and fallo-
UTERINE SEGMENT SHOULD BE TAKEN?
pian tubes should be submitted in toto although there is
SHOULD THEY BE TAKEN HORIZONTALLY
no evidence at the present time to support this practice.
OR VERTICALLY?
Pathologists should be informed of a history of Lynch
syndrome to handle the specimen properly (40–42). The Recommendation
demonstration of clinically occult endometrial carcino- A minimum of 2 sections (1 anterior, 1 posterior)
mas, some being microscopic, underscores the need for should be submitted from the lower uterine segment.
in toto submission of the endometrium in the absence of Longitudinal sections are encouraged as they demon-
macroscopic lesions. Sections should include the endo- strate the relationship with the upper endocervix.
myometrial interface, but the excess myometrium can be Most manuals reviewed advocate the use of
trimmed (40,43). Unremarkable ovaries and fallopian longitudinal sections of the lower uterine segment
tubes should also be submitted in toto until enough (1 anterior/1 posterior) (6).

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 ENDOMETRIAL CARCINOMA, GROSSING AND PROCESSING S17

SHOULD THE PARAMETRIAL unremarkable cervix. In cases of high-grade endome-

TISSUE/PARAMETRIUM BE SAMPLED trial carcinoma or when the tumor is grossly close to
BEFORE OPENING THE UTERUS TO AVOID the cervix, submitting additional sections might be
CARRYOVER? HOW MUCH OF THE TISSUE considered. It is important to submit full thickness
SHOULD BE SUBMITTED? sections of the uterine cervix because the presence of
tumor in the cervical stroma triggers measurement of
Recommendation its depth of invasion in relation to the thickness of the
Parametrial tissue/parametrium should be cervical wall.
sampled before opening the uterus as this approach All manuals reviewed except one advocate the
minimizes the chance of finding carryovers. All of submission of 2 representative sections as indicated
the parametrial tissue/parametrium should be sub- above (6). The Royal College of Pathologists makes
mitted for histologic examination. After inking the a similar recommendation (28). One study found no
parametrial margin, the parametrial tissue/parame- value in submitting more than the standard 2
trium should be blocked in sequential slices. If sections of cervix (1 anterior and 1 posterior) in
macroscopic tumor is seen in the parametrial tissue/ hysterectomies for endometrial cancer without a
parametrium, the most proximal parametrial section gross lesion in the cervix (65). However, a more
should include the adjacent outer portion of the recent publication found that submitting the 2
cervical wall. standard sections of grossly unremarkable cervix
Very few of the manuals address this issue, and, missed 24% of endometrial carcinomas involving the
when mentioned, recommend removing the para- cervix. Of note, in the latter publication, the patient
metrial tissue/parametrium before opening the population was high-risk including patients with
uterus (6). Radical hysterectomies may be under- serous carcinomas, FIGO grade 3 endometrioid
taken in cases of endometrial cancer with an carcinomas, carcinosarcomas, and carcinomas with
epicenter in the lower uterine segment or with lymphovascular invasion (66).
prominent cervical involvement, and, as expected,
this type of specimen will contain parametrium. In
contrast, simple hysterectomies, which are the HOW MANY SECTIONS OF CERVIX SHOULD
specimens obtained for most endometrial carcino- BE TAKEN IF GROSSLY INVOLVED BY
mas, do not usually contain parametrium; however, ENDOMETRIAL CARCINOMA?
a very small amount of parametrial tissue may Recommendation
sometimes be included. At least 2 representative sections of tumor involving
the cervix should be submitted. These sections must
SHOULD THE CERVIX BE AMPUTATED OR include the full thickness of the cervical wall and the
LEFT ATTACHED TO THE CORPUS? ectocervical or vaginal cuff margin.
Documenting involvement of the cervical stroma
Recommendation ensures accurate staging (FIGO stage II) (39). In
The cervix should be left attached to the corpus addition, providing the depth of cervical stromal
during the gross examination of a hysterectomy invasion in relation to the full thickness of the
specimen obtained for endometrial carcinoma. cervical wall might be required for adjuvant therapy
No practice manual recommends amputation of purposes. The following guidelines are used by some
the cervix (6). Amputation could potentially inter- radiation oncology groups: (1) if <3 mm cervical
fere in the pathologic assessment of the tumor and stromal invasion and no other feature suggesting the
the relationship with the upper endocervix, which need for additional adjuvant pelvic irradiation,
can be problematic even at the microscopic patients are treated with vaginal brachytherapy
level (64). only; (2) if invasion into the outer one-third of the
cervical stroma or invasion into the middle one-third
with vascular/lymphatic invasion, adjuvant pelvic
HOW MANY SECTIONS OF THE CERVIX
radiation is recommended; (3) if no evaluation of
SHOULD BE TAKEN IF GROSSLY NORMAL?
lymph nodes was performed at time of surgery,
Recommendation pelvic radiation is recommended for most patients
At least 2 full thickness sections (1 anterior and 1 who have > 2 to 3 mm of cervical stromal invasion,
posterior) should be submitted from a grossly particularly if the tumor is high grade (12).

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S18 A. MALPICA ET AL.

HOW SHOULD A MORCELLATED

HYSTERECTOMY SPECIMEN THAT
CONTAINS AN UNEXPECTED ATYPICAL
ENDOMETRIAL HYPERPLASIA/ EIN OR
ENDOMETRIAL CARCINOMA BE HANDLED?
Recommendation
Gross examination of a morcellated hysterectomy
specimen requires special attention to identify any
endometrial abnormality, although this may be extreme-
ly difficult to see in a morcellated specimen. If such an
abnormality is detected, the entire endometrial lesion and
the adjacent myometrium should be submitted for
microscopic examination. In addition, sampling of
myometrial tissue containing any serosal surface should
be undertaken. If the endometrium appears grossly
unremarkable and the initial representative sections
demonstrate the presence of atypical endometrial hyper-
plasia/EIN or endometrial carcinoma, careful regrossing
is required with the submission of all the visible
endometrial lining and adjacent myometrium. If the
FIG. 7. Sectioning and Extensively Examining the FIMbriated End
morcellated specimen contains the uterine cervix, this protocol, sectioning of adnexa to be submitted for microscopic
should be sampled representatively. examination.
Unexpected endometrial cancer in morcellated
hysterectomy specimens obtained for presumptive benign
conditions is uncommon with a reported incidence
ranging from 0.07% to 3% (67–75). In general, it is submitted in toto in other scenarios—using the guide-
recommended that in such cases a preoperative endo- lines of the SEE-FIM protocol, along representative
metrial biopsy is performed to exclude such a possibility. cross-sections of the remainder of the fallopian tube.
Although the use of endometrial dye instillation, either The SEE-FIM protocol encompasses the following
trypan blue or methylene blue (76,77), has been proposed steps: (1) fixing the specimen for several hours, (2)
as a useful technique to facilitate the identification of the amputating the distal 2 cm—the infundibulum and
endometrium in morcellated hysterectomies, this is not fimbrial end, and sectioning parallel to the long axis of
commonly done. When an occult cancer is picked up in a the fallopian tube, (3) taking cross sections at 2 to 3
morcellated specimen, it may be very difficult to assess mm intervals of the rest of the tube—the isthmus and
the depth of myoinvasion and thus accurate staging of ampulla, (4) sectioning the ovary perpendicularly to
the endometrial cancer may not be possible (78). its long axis at 2 to 3 mm intervals and (5) to examine
one hematoxylin and eosin (H&E)-stained slide per
block (7) (Fig. 7). Although this system is being used
HOW THOROUGHLY SHOULD THE
for all endometrial cancers at some institutions (79),
FALLOPIAN TUBES BE EXAMINED?
and its universal use in endometrial cancer is
Recommendation advocated by some investigators (80,81), at this
Gross examination of the fallopian tube must be point there is not enough evidence to support its
carefully undertaken and any areas with macroscopic mandatory application regardless of histologic type
abnormalities should be submitted for microscopic (82). Of note, it has been stated that expenses
examination. If the fallopian tube is unremarkable, the secondary to complete processing are relatively
entire tube should be submitted for microscopic minor when balanced against potential expenses of a
examination using the SEE-FIM protocol. Should this recurrence (82). A practical alternative is to ensure
not be possible in all cases of endometrial cancer, the that at least the fimbrial end of the fallopian tube, as
SEE-FIM protocol should be used if uterine serous per the SEE-FIM protocol, is examined in addition to
carcinoma, clear cell carcinoma and carcinosarcoma the usual representative sections of the rest of the
are present, while only the fimbrial end should be fallopian tube (28,83).

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 ENDOMETRIAL CARCINOMA, GROSSING AND PROCESSING S19

HOW MUCH OF A NORMALLY SIZED AND advocate for submission of one representative section
GROSSLY UNREMARKABLE OVARY SHOULD per 2 or 3 cm of maximal omental dimension if the
BE SUBMITTED? omentum is grossly unremarkable (73). One study
found that submitting 5 blocks of grossly negative
Recommendation
omentum has a sensitivity of 82% while examining 10
Gross examination of the ovary must be carefully
blocks raises the sensitivity to 95% (87).
performed. If serous carcinoma, clear cell carcinoma or
carcinosarcoma, the entire ovary should be submitted
after slicing it perpendicularly to its long axis at 2 to 3 HANDLING OF LYMPH NODES
mm intervals. If possible, the same protocol should
Recommendations
be used for oophorectomy specimens accompanying
Lymph nodes from different anatomical sites should
hysterectomies for other endometrial cancer histotypes.
be sent in separate appropriately labelled specimen
Should the latter not be possible, at least 2 sections of
containers and handled separately. They should be
each ovary should be submitted. carefully dissected from the adipose tissue. This can be
Some investigators advocate the universal use of the
done with a thorough visual examination and palpation.
SEE-FIM protocol to handle grossly unremarkable
Clearing solutions are not routinely recommended as
adnexa for endometrial cancer (79,81). Others proposed
they are not usually necessary. A small amount of
that regardless of histotype, the ovaries should be
adipose tissue should be left around larger lymph nodes
submitted in toto if they are small and unremarkable;
to evaluate the presence or absence of extranodal
should they not be small, at least 2 sections should be
extension. Lymph nodes up to 2 mm are embedded
submitted (84). Of note, one study found that 2.7% of
whole. If larger than 2 mm, they should be sliced in neat,
grossly unremarkable ovaries removed as part of the parallel slices at 2 to 3 mm intervals—slicing should be
surgical treatment for endometrial cancer harbor micro-
perpendicular to the long axis of the node. All grossly
scopic carcinoma (82).
unremarkable lymph node tissue should be submitted for
microscopic examination in properly identified cassettes.
HOW MANY SECTIONS OF OMENTUM
The number of lymph nodes submitted per cassette and
SHOULD BE EXAMINED HISTOLOGICALLY
the way they have been submitted, for example in toto—
WHEN REMOVED FOR STAGING PURPOSES
if very small, or sectioned, should be specified in the
IN CASES OF SOME ENDOMETRIAL
section code. With grossly positive lymph nodes,
CARCINOMA HISTOTYPES? representative sections to demonstrate the largest size
Recommendation of tumor involvement as well as the surrounding adipose
Omentectomy is part of the staging procedure of tissue should be submitted for microscopic examination
endometrial serous carcinoma, clear cell carcinoma and and noted in the section code.
carcinosarcoma. The gross appearance and measurement Nodal involvement is one of the most powerful
of the omentum should be provided. Omental tissue prognostic determinants in all cancers, and it predicts
should be sliced at 0.5 cm intervals to detect small distant recurrences in low-risk endometrial carcinoma
abnormalities. There are no standard sampling recom- (88). At the same time systematic pelvic (+/− para-
mendations, but in general the number of sections to be aortic) nodal dissection, which is associated with
submitted will depend on the gross examination findings. significant morbidity, has demonstrated no survival
If the omentum is grossly positive, one or 2 representative benefit (89,90). and practices vary worldwide for this
sections are enough for microscopic evaluation, but if it is reason. The proper retrieval of lymph nodes can be
grossly negative, one representative section per 2 or 3 cm achieved with a thorough examination by direct vision,
of maximal omental dimension (85) or at least a total of 4 palpation, and sharp dissection and does not require the
blocks of tissue should be submitted (28). use of clearing solutions (91). Slicing lymph nodes
Currently, guidelines on omental tissue sampling in perpendicular to their long axis at 2 mm intervals
endometrial cancer are included in the Dataset for increases the chance of detecting metastases (92,93).
Histological Reporting of Endometrial Cancer by the Submitting a rim of adipose tissue around the lymph
Royal College of Pathologists (28), but not included in nodes allow the assessment of extracapsular extension
the recommendations of either the CAP (11) or the when there is tumor involvement. The latter finding has
International Collaboration on Cancer Reporting (86) been reported to be an important prognostic factor in
The former recommends submission of a total of 4 FIGO stage IIIC endometrial carcinoma by some
blocks of tissue if grossly negative omentum. Others, investigators (94).

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S20 A. MALPICA ET AL.

emanate from the parametrial tissue, this is followed by

excision of all mapped SLNs; (5) any suspicious non-
SLN should be excised and frozen section may be
required to determine if a para-aortic lymphadenectomy
will be performed. Of note, routine frozen section of
SLNs is not advisable as small foci of tumor may be lost
when cutting the frozen section slides in addition to the
relatively low sensitivity for detection of metastases in
grossly unremarkable lymph nodes, (6) should mapping
failure occur in a hemi-pelvis, a side-specific lymphade-
nectomy should be performed; (7) pathology ultrastaging
is required to improve the detection of low-volume
metastases (57,95). The 2018 NCCN guidelines also state
that recent evidence indicates that SLN mapping may be
FIG. 8. Sentinel lymph node, parallel slices are perpendicular to the used in high-risk histologies (serous carcinoma, clear cell
long axis of the specimen. carcinoma, and carcinosarcoma) (57). At the present
time, it has been established that the use of indocyanine
green, which requires use of a near infra-red camera for
HANDLING OF SLNS
localization, has similar rates of mapping success to those
Recommendations of radiocolloid Tc-99 combined with blue dye (95). The
The description of the SLN should include measure- gross processing of SLNs is critical to ensure the success
ments, gross appearance, the presence of dye and the of this technique. It is of utmost importance to obtain
radioactive tracer reading provided by the surgeon, if serial perpendicular, thin (2.0 mm) sections as an initial
any. The lymph node is sliced at 2.0 mm intervals step as this raises the odds of metastatic tumor detection
perpendicular to its long axis (Fig. 8). A small rim of independent of the ultrastaging process (84). This
adipose tissue should be left around the lymph node. method not only facilitates the examination of the lymph
The entire lymph node is submitted for microscopic node subcapsular space and parenchymal surface, but is
examination in properly identified cassettes. The SLN designed to detect all metastases > 2.0 mm. A study
is usually ultrastaged [i.e. additional recuts and/ comparing 2 different ultrastaging protocols (method #1,
or immunohistochemistry (IHC) for keratin], although obtaining 5 H&E-stained levels at 250 μm with 2
some institutions do not routinely undertake ultrastaging. unstained slides at each level—pankeratin IHC per-
At the present time there is no universal ultrastaging formed on level 1 in cases with negative H&E or method
protocol; however, all institutions undertaking SLN #2, 1 H&E level and 2 unstained slides cut at 250 μm
examination should have a standard procedure for SLNs into the tissue block, pankeratin IHC performed in cases
in endometrial cancer. with negative H&E) found no statistically significant
SLN removal has been introduced in the surgical differences between the methods with respect to number
staging of endometrial carcinoma to decrease the of positive SLNs detected, size of metastasis or false-
morbidity secondary to a lymphadenectomy but still negative rate (84).
obtain information about the lymph node status (95). There is no universal protocol for the ultrastaging
The 2018 NCCN Guidelines indicate that SLN mapping of SLNs (95). Protocols used at the 2 largest cancer
may be considered in patients with apparent uterine- centers in the United Stated are as follows:
confined endometrial cancer (clinical stage I disease) (57).
As delineated in the NCCN guidelines and the Society of (1) The University of Texas M.D. Anderson Cancer
Gynecologic Oncology recommendations, there are Center Protocol.
several key points when using this technique: (1) the
expertise of the surgeon and attention to technical detail If the H&E-stained slide is negative for tumor, 3
are critical to ensure mapping success; (2) superficial and consecutive sections at 250 µm into the paraffin block
deep cervical injection of dye has been validated as a are obtained (one for H&E and one of the remaining 2
useful mapping technique; (3) complete evaluation of the to be used for keratin cocktail IHC if the additional
peritoneal cavity is mandatory; (4) SLN dissection starts H&E-stained slide is negative (96) (Fig. 9A).
with the evaluation of the retroperitoneal spaces and
identification of the sentinel drainage pathways that (1) Memorial Sloan Kettering Cancer Center Protocol.

Int J Gynecol Pathol Vol. 38, No. 1 Supplement 1, January 2019

 ENDOMETRIAL CARCINOMA, GROSSING AND PROCESSING S21

FIG. 9. Ultrastaging protocols, MD Anderson Cancer Center (MDACC) (A) and Memorial Sloan Kettering Cancer Center (MSKCC),
ultrastaging will be obtained if there is myometrial or vascular/lymphatic invasion (*) (B). H&E indicates hematoxylin and eosin; IHC,
immunohistochemistry; SLN, sentinel lymph node.

If the initial H&E-stained slide is negative for containing the deepest point of myometrial invasion for
carcinoma and the endometrial cancer is myoinvasive frozen section. Should cervical, uterine serosal or
or associated with vascular/lymphatic invasion, 2 addi- adnexal involvement be suspected, submit appropriate
tional levels 50 µm apart are examined, at each level 2 sections for frozen section examination.
slides are obtained, one for H&E and the second Intraoperative evaluation of hysterectomy and
for keratin cocktail IHC if the H&E-stained slide is bilateral salpingo-oophorectomy specimens obtained
negative (97) (Fig. 9B). for endometrial cancer to determine parameters that
guide lymph nodes dissection, and in some cases
REPORTING MARGINS OF HYSTERECTOMY omentectomy, which are needed for staging and
SPECIMENS FOR ENDOMETRIAL CANCER prognosis, is commonly performed in the United
Recommendations States, and much less frequently, if at all, in other
The ectocervical margin of a hysterectomy specimen parts of the world (31). Histotype, tumor grade if
should be reported in an endometrial cancer with applicable, and depth of myometrial invasion are
cervical involvement. The vaginal cuff and parametrial typically reported (31). In addition, tumor size needs
margins should be reported in endometrial carcinomas to be determined if the Mayo algorithm is being
with cervical and/or parametrial involvement when a applied. Briefly, using this algorithm cases are stratified
radical hysterectomy is undertaken. Otherwise, reporting as low risk or high risk. Low risk is defined as FIGO
of margins is optional (11). In cases where it is required grade 1 or 2 endometrioid carcinoma with myometrial
to report the above margins, including the distance invasion ≤ 50% and primary tumor diameter ≤ 2 cm
between the tumor and the margin is also optional (11). while high risk is defined as FIGO grade 3 endome-
Involvement of the uterine serosa by tumor should be trioid carcinoma, nonendometrioid histotype, myome-
reported as this finding indicates FIGO stage III A trial invasion > 50% or primary tumor diameter > 2
disease (39); however, the uterine serosa is not a margin cm. Cases in the low risk category are spared a
and should not be designated as such. systematic pelvic and para-aortic lymphadenectomy
while these procedures are performed in cases in the
INTRAOPERATIVE ASSESSMENT high risk category (21). Lower uterine segment,
cervical, and adnexal involvement and lymphovascular
Recommendations space invasion should be reported if these findings are
In cases where intraoperative assessment is requested identified during the intraoperative evaluation.
by the surgeon to determine whether staging will be
obtained, examine the specimen carefully, including the
CONCLUSIONS
uterine serosa, lower uterine segment, cervix and
adnexal structures. Identify the lesion, measure it, It is our hope that these ISGyP developed recom-
cross-section the uterine wall, and evaluate the status mendations will help to standardize the processing of
of the myometrium. Submit at least one section of the endometrial cancer specimens; this will facilitate accu-
lesion for frozen section including the adjacent uterine rate pathologic reporting and a better understanding of
wall. Should myometrial invasion be suspected, submit this disease which will be to the ultimate benefit of
the lesion and the full thickness of the uterine wall patients suffering from it.

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S22 A. MALPICA ET AL.

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