Protocol applies to all carcinomas of the
endometrium.
Procedures
Cytology
Biopsy
This protocol is intended to assist pathologists in
providing clinically useful and relevant information as a result of the
examination of surgical specimens. Use of this protocol is intended to be
entirely voluntary. If equally valid protocols or similar documents are
applicable, the pathologist is, of course, free to follow those authorities.
Indeed, the ultimate judgment regarding the propriety of any specific procedure
must be made by the physician in light of the individual circumstances
presented by a specific patient or specimen.
It should be understood that adherence to this
protocol will not guarantee a successful result. Nevertheless, pathologists are
urged to familiarize themselves with the document. Where a physician chooses to
deviate from the protocol based on the circumstances of a particular patient or
specimen, the physician is advised to make a contemporaneous written notation
of the reason for the procedure followed.
The College recognizes that this document may be
used by hospitals, attorneys, managed care organizations, insurance carriers,
and other payers. However, the document was developed solely as a tool to
assist pathologists in the diagnostic process by providing information that reflects
the state of relevant medical knowledge at the time the protocol was first
published. It was not developed for credentialing, litigation, or reimbursement
purposes. The College cautions that any uses of the protocol for these purposes
involve considerations that are beyond the scope of this document.
I. Cytologic material back Top Main Page
A. Clinical Information
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) previous diagnosis, treatment or procedure (Note A)
(2) menstrual history, including date of last
normal period
(3) previous/current pregnancy history
(4) exogenous hormones, including type and
duration
b. Relevant findings (e.g. intraoperative,
hysteroscopic, radiologic, laboratory)
c. Clinical diagnosis
d. Procedure
(1) cervical smear
(2) vaginal pool aspiration
(3) endocervical or direct endometrial sampling
(specify technique)
(4) peritoneal washing
(5) fine needle aspiration (specify and describe
site)
(6) scraping of diaphragmatic or peritoneal surface (specify if gross
lesion present)
B. Macroscopic
Examination
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Number of slides received, if appropriate
c. Quantity and appearance of fluid specimens,
if appropriate
d. Other (e.g. cytologic preparation from
tissue)
e. Results of intraprocedural consultation
2. Material submitted for microscopic evaluation
(e.g. smear, cytocentrifuge, touch or filter preparation, cell block)
3. Special studies (specify) (e.g.
cytochemistry, immunocytochemistry, DNA analysis [specify type], morphometry,
cytogenetic analysis)
C. Microscopic evaluation
1. Adequacy of specimen (if unsatisfactory for
evaluation, specify reason) (Note B)
2. Tumor, if present
a. Histologic type of tumor, if possible (Note C)
b. Other characteristics (e.g. degree of
differentiation)
3. Additional pathologic findings, if present
4. Results/status of special studies (specify)
5. Comments
a. Correlation with intraprocedural
consultation, as appropriate
b. Correlation with other specimens, as
appropriate
c. Correlation with clinical information, as
appropriate
II. Biopsy and Curettage back Top Main Page
A. Clinical Information
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) previous diagnosis, treatment or procedure (Note A)
(2) menstrual history, including date of last
normal period
(3) previous/current pregnancy history
(4) exogenous hormones, including type and
duration
b. Relevant findings (e.g.
intraoperative, hysteroscopic, radiologic, laboratory)
c. Clinical diagnosis
d. Procedure (e.g. biopsy,
fractional curettage, polypectomy)
e. Site of specimen (e.g.
endometrium, endocervix)
B. Macroscopic Examination
1. Specimen
a Unfixed/fixed (specify fixative)
b. Size (if multiple pieces, aggregate
dimensions or size range of pieces: distinguish tissue from blood, if possible)
c. Results of intraoperative
consultation
2. Tumor, if discernible (e.g.
consistency or necrosis)
a. Dimensions
b. Other descriptive features
3. Tissue submitted for microscopic evaluation (Note D)
4. Special studies (specify) (e.g. estrogen/
progesterone receptors, immunohisto-chemistry, flow cytometry, morphometry,
cytogenetic analysis)
C. Microscopic Examination
1. Adequacy of specimen (if inadequate for
evaluation, specify reason) (Note E)
2. Tumor
a. Histologic type(s) (Note C)
b. Histologic grade (Note F)
c. Extent (proportion of specimen involved or
dimensions if small and measurable)
3. Additional pathologic findings, if present
a. Hyperplasia (specify type) (Note
C)
b. Metaplasia (specify type)
c. Others(s)
4. Results/status of special studies (specify)
5. Comments
a. Correlation with intraoperative consultation,
as appropriate
b. Correlation with other specimens, as
appropriate
c. Correlation with clinical information, as
appropriate
III. Hysterectomy back Top Main Page
A. Clinical Information
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) previous diagnosis, treatment or procedure (Note A)
(2) menstrual history, including date of last
normal period
(3) previous/current pregnancy history
(4) exogenous hormones, including type and duration
b. Relevant findings (e.g. intraoperative, hysteroscopic,
radiologic, laboratory)
c. Clinical diagnosis
d. Procedure (e.g. hysterectomy
with bilateral salpingo-oophorectomy and pelvic lymph node sampling)
B. Macroscopic Examination
1. Specimen
a. Organ(s)/tissue(s) included
b. Unfixed/fixed (specify fixative)
c. Number of pieces
d. Dimensions (three)
e. Orientation (if indicated by surgeon)
f. Results of intraoperative consultation
2. Uterine tumor
a. Location (e.g. fundus/right cornu/isthmus)
b. Dimensions (three)
c. Descriptive characteristics (e.g. exophytic/necrosis)
d. Distance from margins
e. Estimated extent of invasion (Note
G)
3. Uninvolved uterus
a. Dimensions
b. Appearance of:
(1) endometrium
(2) myometrium, including thickness
(3) serosa
(4) cervix
c.
Additional pathologic findings, if
present
4. Fallopian tubes
a. Tumor, if present
(1) dimensions
(2) location and relation to uterine tumor
b. Resection margins, as appropriate
c. Other pathologic findings, if present
5. Ovary(ies)
a. Tumor, if present (see Ovary protocol)
(1) dimensions
(2) location and relation to uterine tumor
b. Resection margins, as appropriate
c. Other pathologic findings, if present
6. Regional lymph nodes
a. Location (if specified by surgeon)
b. Number at each location
c. Descriptive features of grossly involved
nodes at each location
7. Other organs and tissues, including biopsy
specimens with location specified by surgeon
a. Descriptive features
b. Tumor, if present
(1) dimensions
(2) location and relation to uterine tumor
c. Resection margins, as appropriate
d. Other pathologic findings
8. Tissues submitted for microscopic evaluation
a. Carcinoma, including section(s) to
demonstrate:
(1) deepest invasion of myometrium (See Figure 1)
(2) distance from serosa (if thickness of myometrium
or depth of tumor is not known, extent may
be specified as distance in mm from the serosa)
(3) most inferior level of involvement
(4) interface with adjacent uninvolved endometrium
and myometrium
b. Uninvolved endo-myometrium
c. Cervix including endocervical and exocervical
portions
d.
Resection margin, as appropriate
(1) cervical or vaginal
(2) parametrial
(3) other(s)
e. Additional uterine lesions, if present
f. Lymph nodes at least one section of each
g. Staging biopsy specimens one section of
each
h. Omentum several sections if grossly
negative; otherwise representative sampling
i. Frozen tissue fragment(s) (unless saved for
special studies)
j. Other organs and tissues
(1) Tumor present sections adequate to demonstrate:
i. histologic type and grade of tumor
ii. relation to uterine tumor and resection
margins (if appropriate)
(2) Tumor absent
i. routine sections
ii. sections through previous site of tumor, if
discernible
(3) Other pathologic lesions, as appropriate
9. Special studies (specify) (e.g. DNA ploidy,
hormone receptors, oncogene evaluation)
C. Microscopic Examination
1. Uterus
a. Tumor
(1) histologic type (Note C)
(2) histologic grade (Note F)
(3) extent of invasion (Note G)
(4) blood/lymphatic vessel invasion
b. Additional pathologic findings, if present
(1) hyperplasia (specify type) (Note
C)
(2) endometrial intraepithelial carcinoma (EIC
particularly associated with serous carcinomas)
(3) adenomyosis, with/without tumor (extension of
tumor into adenomyosis is not considered true myometrial invasion but is
reported separately)
c. Margins
(1) cervical or vaginal
(2) parametrial
(3) other(s)
2. Regional lymph nodes
a. Number at each site (Note G)
b. Number involved by tumor at each site
c. Additional findings (e.g. glandular inclusions)
3. Other organs and tissues including staging
biopsy specimens (specify)
a. Tumor, if present (Note G)
(1) histologic type, if different from main tumor
(2) histologic grade, if different from main tumor
(3) consistent with
i. direct extension
ii. metastasis
iii. separate primary tumor
(4) site
(5) extent
(6) relation to resection margins
b. Additional pathologic findings, if present
c. Results/status of special studies (specify)
4. Comments
a. Correlation with intraoperative consultation,
as appropriate
b. Correlation with other specimens, as
appropriate
c. Correlation with clinical information, as
appropriate
EXPLANATORY NOTES
A. Previous Diagnoses back
Top Main
Page
Slides of previous pertinent specimens should be
made available to the pathologist if their review is deemed essential by the
surgeon or pathologist for optimal interpretation of the present specimen.
B. Adequacy of Cytology Sample for
Microscopic Evaluation back Top Main Page
If a cytologic sample is procured by a transvaginal
procedure other than direct endometrial sampling, the absence of endometrial
cells does not signify specimen inadequacy.
C. Histologic Type back
Top Main
Page
The World Health Organization (WHO) Histologic
Classification of Endometrial Carcinoma and Hyperplasia(1) is shown
below.
Carcinoma
Endometrioid
carcinoma
- Adenocarcinoma
- Secretory (variant)
- Ciliated cell (variant)
- Adenocarcinoma with squamous
differentiation
- (Adenoacanthoma)
- (Adenosquamous carcinoma)
Serous
adenocarcinoma
Clear
cell adenocarcinoma
Mucinous
adenocarcinoma
Squamous
cell carcinoma
Mixed
carcinoma*
Undifferentiated
carcinoma
*A carcinoma (other than adenocarcinoma with
squamous differentiation) in which one or more additional types of tumor
account for at least 10% of the entire tumor. The diagnosis is optimally made
on examination of a hysterectomy specimen, but if only a smaller specimen is
available, any amount of a second tumor category suffices for the diagnosis.
When a carcinoma is classified as mixed, the major and minor types and their
relative proportions should be specified.
Hyperplasia
Simple
Complex
(adenomatous)
Atypical hyperplasia
Simple
Complex
(adenomatous with atypia)
D. Tissue Submitted for
Microscopic Evaluation back Top Main Page
All biopsy or curettage tissue is generally
submitted, often in an embedding bag. The blood may be removed before
submission either with a clean forceps or by gentle washing in saline solution.
E. Adequacy of Biopsy/Curettage
Material back Top Main Page
It should be noted that adequacy varies both with
the procedure (e.g. more tissue expected from a curettage than an outpatient
biopsy) and the diagnosis (e.g. atrophic endometrium generally yields scanty
specimens even at curettage). If the
tissue obtained is not representative of functioning endometrium (e.g.
endocervix, lower uterine segment, or surface endometrium only), this fact
should be specified.
F. Histologic Grading back
Top Main
Page
The glandular component of all endometrioid
carcinomas is graded as follows(1):
Grade X: Cannot be assessed
Grade 1: 5% or less non-squamous solid
growth pattern
Grade 2: 6%-50% non-squamous solid
growth pattern
Grade 3: More than 50% of a non-squamous
solid growth
pattern
Notable nuclear atypia inappropriately severe for
the architectural grade of the tumor raises the grade of otherwise Grade 1
tumors by one.
Comment: Serous, clear cell, and undifferentiated
carcinomas are high-grade and need not be graded. No universally accepted criteria
exist for grading of mucinous adenocarcinomas, but if graded by the same
criteria listed above for endometrioid adenocarcinomas, they are almost all
Grade 1. The squamous component of endometrioid adenocarcinoma with squamous
differentiation is generally not graded.
G. TNM and FIGO Staging of Endometrial Carcinoma(2,3)
back Top Main Page
The TNM Staging System for endometrial cancer endorsed
by the American Joint Committee on Cancer (AJCC) and the International Union
Against Cancer (UICC) and the parallel system formulated by the International
Federation of Gynecology and Obstetrics (FIGO) are recommended as shown below.
TNM* FIGO Definition
Category Stage
TX (--) Primary tumor cannot be
assessed
T0 (--) No evidence of primary tumor
Tis 0 Carcinoma in situ
T1 I Tumor confined to corpus
uteri
T1a IA
Tumor limited to
endometrium
T1b IB Tumor invades up to or less
than
one half of the
myometrium
T1c IC Tumor invades to more than
one
half of the myometrium
T2 II
Tumor invades cervix,
but
does
not extend beyond uterus
T2a IIA
Endocervical glandular
involvement
only
T2b IIB Cervical stromal invasion
T3 III
Local and/or regional
spread
as
specified in T3a, b, N1 and
FIGO
IIIA, B and C below
T3a IIIA
Tumor involves serosa
and/or
adnexa
(direct extension or
metastasis)
and/or cancer
cells
in ascites or peritoneal
washings
T3b IIIB Vaginal involvement (direct
extension
or metastasis)
N1 IIIC Metastasis to the pelvic
and/or
Para-aortic
lymph nodes
T4** IVA Tumor invades bladder
mucosa**
and/or bowel
mucosa**
M1 IVB Distant metastasis***
*By AJCC/UICC convention, the designation T
refers to a primary tumor that has not been previously treated. The symbol p
refers to the pathologic classification of the TNM, as opposed to the clinical
classification and is based on gross and microscopic examination. pT entails a resection of the primary tumor
or biopsy adequate to evaluate the highest pT category; pN entails removal of
nodes adequate to validate lymph node metastasis; and pM implies microscopic
examination of distant lesions.
Clinical classification (cTNM) is usually carried out by the referring
physician before treatment during initial evaluation of the patient or when
pathologic classification is not possible.
Tumor
Remaining in the Patient
Tumor remaining in a patient after therapy with
curative intent (e.g., surgical resection for cure) is categorized by a system
known as R classification, shown below.
RX Presence
of residual tumor cannot
be
assessed
R0 No
residual tumor
R1 Microscopic
residual tumor
R2 Macroscopic
residual tumor.
For the surgeon, the R classification may be
useful to indicate the known or assumed status of the completeness of a
surgical excision. For the pathologist,
the R classification is relevant to the status of the margins of a surgical
resection specimen. That is, tumor
involving the resection margin on pathologic examination may be assumed to
correspond to residual tumor in the patient and may be classified as
macroscopic or microscopic according to the findings at the specimen margin(s).
Tumor
Remaining in a Specimen
In contrast, tumor remaining in a resection
specimen from a patient who has undergone previous (neoadjuvant) treatment of
any type (radiation therapy alone, chemotherapy therapy alone, or any combined modality
treatment) is codified by the TNM using a prescript y (e.g., ypT1). Thus, yTNM indicates the post-treatment
status of the tumor. For many
neoadjuvant therapies, the classification of residual disease may be a strong
predictor of postoperative outcome. In
addition, the ypTNM classification provides a standardized framework for the
collection of data needed to accurately evaluate new neoadjuvant therapies.
Locally
Recurrent Tumor
In contrast to residual tumor, classification
of a tumor as recurrent requires a documented disease-free interval after
definitive therapy. Recurrent tumor may
also be classified according to the TNM categories, but the prefix r (e.g.,
rpT1) is used to indicate the recurrent status of the tumor.
**Presence of bullous edema is not sufficient
evidence to classify a tumor as T4.
***Excludes metastasis to vagina, pelvic serosa,
or adnexa; includes metastasis to intra-abdominal lymph nodes other than
para-aortic and/or inguinal lymph nodes.
Regional
Lymph Nodes (N) : TNM Staging System
NX Regional
lymph nodes cannot be assessed
N0 No
regional lymph node metastasis
N1 Regional
lymph node metastasis
Regional
lymph nodes include the pelvic, hypogastric (obturator), common iliac, external
iliac, internal iliac, parametrial, sacral, and para-aortic lymph nodes.
Distant
Metastasis (M): TNM Staging System
MX Distant
metastasis cannot be assessed
M0 No
distant metastasis
M1 Distant
metastasis
AJCC/UICC
TNM STAGE GROUPINGS and FIGO STAGES
AJCC/UICC FIGO
Stage 0 Tis
N0 M0
Stage IA T1a N0 M0 Stage IA
Stage IB T1b N0 M0 Stage IB
Stage IC T1c N0 M0 Stage IC
Stage IIA T2a N0 M0 Stage IIA
Stage IIB T2b N0 M0 Stage IIB
Stage IIIA T3a N0 M0 Stage IIIA
Stage IIIB T3b N0 M0 Stage IIIB
Stage IIIC T1 N1 M0 Stage IIIC
T2 N1 M0
T3a,b N1 M0
Stage IVA T4 Any N M0 Stage IVA
Stage IVB Any T Any N M1 Stage IVB
1. Scully
RE, Bonfiglio TA, Kurman RJ, Silverberg SG, Wilkinson EJ. Histological Typing
of Female Genital Tract Tumours. In: World Health Organization: International
Histological Classification of Tumours. New York: Springer-Verlag; 1994.
2. Fleming
ID, Cooper JS, Henson DE, et al. eds. AJCC Manual for Staging of Cancer. 5th
ed. Philadelphia, PA: Lippincott Raven; 1997.
3. Pettersson
F. Annual report of the results of treatment in gynecological cancer.
Stockholm: International Federation of Gynecologic and Obstetrics; 1991.
BIBLIOGRAPHY
Silverberg
SG, Kurman RJ. Tumors of the Uterine Corpus. In: Atlas of Tumor Pathology. 3rd
series. Fascicle 3. Washington, DC: Armed Forces Institute of Pathology; 1992.
Silverberg
SG, Tabbara SO. The Uterine Corpus. In: Silverberg SG, ed. Principles and
Practice of Surgical Pathology. 3rd ed. New York: Churchill Livingstone;
1997:2459-2524.
Author:
Steven G. Silverberg, MD
©2000. College of American Pathologists (CAP). All rights reserved. None of the contents of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without prior written permission of the publisher.
Expires as CAP policy in May 2001. A year prior, the
protocol will be reviewed and updated.
Contributors:
CAP Cancer Committee; Donald E. Henson, MD; Enrique Hernandez, MD; Maureen Killacky, MD; Beverly B. Kramer, MD; Rachelle Lanciano, MD; Janice M. Lage, MD; Stanley J. Robboy, MD; Stephen G. Ruby, MD; Robert E. Scully, MD; Richard Zaino, MD