The International Federation of Obstetricians and Gynecologists 1971 staging system for tumors of the uterine corpus 3 Stage Characteristics 0 Carcinoma in situ I The carcinoma is confine
Trang 1Review Article FIGO Staging of Endometrial Adenocarcinoma:
A Critical Review and Proposal
Summary: The optimal staging of tumors would reflect their biology and patterns of spread, permit accurate prognostication, and facilitate therapeutic decision-making The last revision of the International Federation of Obstetricians and Gynecologists (FIGO) staging of uterine corpus tumors was in 1988, and it represented the transition from a clinical to a surgico-pathologic system With 20 years of experience, we can now review the accuracy, reproducibility, and utility of this system Pathologists are in a unique position to study each of these characteristics, comment on their ability to apply the criteria in daily practice, and offer suggestions to further improve the FIGO system
This paper selectively reviews some of the more problematic aspects of the current FIGO system, including the following: the distinction of tumors confined to the endometrium from those which are superficially myoinvasive; the method and utility of histologic grading of endometrial adenocarcinoma; the utility and reproducibility of the diagnosis of cervical epithelial and stromal invasion; the striking heterogeneity within and among stage III A, B, and C tumors and their differing prognostic significance It concludes with recommendations for changes in a future revision of the FIGO staging
of endometrial carcinoma Key Words: Endometrium—Carcinoma—FIGO—Stage
In 1988, the International Federation of
Obstetri-cians and Gynecologists (FIGO) made significant
changes to the staging scheme for cancers of the
uterine corpus (1), replacing the clinically based 1970
classification (2,3) with a surgico-pathologic system
(Tables 1, 2) This occurred in part because of a
change during the previous decade in the clinical
management of endometrial carcinoma, with surgery
replacing radiation therapy as the primary
therapeu-tic modality This newer staging system represented
a dramatic improvement, as the older system was
inaccurate and neither highly predictive nor highly
reproducible Two examples of the improvement in
prognostication and accuracy follow Wolfson et al
(4) retrospectively compared the prognostic signifi-cance of surgical staging with clinical staging The 5-year survival rate by clinical stage was as follows: stage I—87%, stage II—86%, stage III—0%, and stage IV—0% Only 5% of women had stage III or
IV disease In contrast, the 5-year survival rate by surgical stage demonstrated far better discrimination,
as follows: stage I—91%, stage II—86%, stage III— 58%, and stage IV—0% The clinically defined stage was retrospectively reassigned after examination of the surgical specimen in 25% of the cases, and 16%
of the women were found to actually have stage III or
IV disease Creasman et al (5) examined the accuracy
of the designation of clinical stage II endometrial adenocarcinoma using data from a large Gynecologic Oncology Group (GOG) protocol In the FIGO system of 1970, clinical stage II disease had been defined as spread of carcinoma to the cervix based upon the results of pelvic examination of the cervix or fractional curettage Of 148 women found to have stage II carcinoma clinically, as previously defined,
From the Department of Pathology, M.S Hershey Medical
Center, Penn State University, Hershey, Pennsylvania.
Address correspondence and reprint requests to Richard J.
Zaino, MD, Department of Pathology, M.S Hershey Medical
Center, Penn State University, Hershey, PA 17033 E-mail:
rzaino@psu.edu.
Trang 2only 66 actually had tumor present in the cervix in the
hysterectomy specimen Thirty-one of these women
also had clinically occult extrauterine disease
Con-sequently, only 35 (24%) of those assigned as clinical
stage II disease actually had a carcinoma that had
spread to the cervix alone
The transition from clinical staging to
surgico-pathologic staging of tumors of the uterine corpus
thus represented a significant advance in
prognos-tication and determination of need for additional
therapy The use of a surgico-pathologic system also
provides an opportunity and an obligation for
pathologists to become integral in the assessment
and further refinement of the staging system, as it is
only with meticulous examination of the surgically
derived tissue that accurate assignment of stage is
possible It is the purpose of this paper to selectively
review some of the less reproducible and more
challenging or contentious aspects of the current
staging system, and to provide some suggestions for
consideration when the staging is next under revision
STAGE I (TUMORS CONFINED TO THE UTERINE CORPUS) Although it is usually not difficult to determine when a tumor is confined to the uterine corpus (stage I), the stage is subdivided into those which are confined to the endometrium (stage IA), those which invade the inner-half of the myometrium (stage IB), and those which invade the outer-half of the myometrium but do not extend to the uterine serosa (stage 1C) In contrast to tissues such as the colon, where a muscularis mucosa clearly separates the mucosa from the submucosa, the interface of the endometrium and myometrium is often vague and irregular Irregular and often sinuous interdigitations
of the endometrium with the myometrium are the rule rather than the exception (Fig 1) This archi-tectural complexity is compounded by the fact that invasive well-differentiated endometrial adenocarci-nomas often do not display incomplete glands, individual cell permeation, or a desmoplastic host response The neoplastic glands of tumors actually confined to the endometrium often over-run and replace the endometrial stroma in these interdigita-tions (Figs 2A, B), and consequently the assessment
of superficial myometrial invasion is problematic (6) Anecdotal reports suggest that most pathologists prefer to overestimate rather than underestimate the depth of invasion; so superficial invasion is probably frequently overdiagnosed This impression is sup-ported by the observation that the most recent FIGO data indicates almost identical 5-year survival data for women with stage IA (91%) and stage IB (90%) tumors (7)
TABLE 1 The International Federation of Obstetricians
and Gynecologists 1971 staging system for tumors of the
uterine corpus (3)
Stage Characteristics
0 Carcinoma in situ
I The carcinoma is confined to the corpus
Ia The length of the uterine cavity is 8 cm or less
Ib The length of the uterine cavity is more than 8 cm
Stage I cases should be subgrouped with regard to the
histologic grade of the adenocarcinoma
II The carcinoma has involved the corpus and the cervix
III The carcinoma has extended outside of the uterus but
not outside of the true pelvis
IV The carcinoma has extended outside of the true pelvis or
has involved the mucosa of the bladder or rectum
TABLE 2 The International Federation of Obstetricians
and Gynecologists 1988 staging system for tumors of the
uterine corpus (1)
Stage Characteristics
IA G123 Invasion confined to the endometrium
IB G123 Invasion confined to the inner half of myometrium
IC G123 Invasion to outer half of myometrium
IIA Endocervical glandular involvement only
IIB Cervical stromal invasion
IIIA Tumor invades uterine serosa, adnexa, and/or
positive peritoneal cytology
IIIB Vaginal metastasis
IIIC Metastasis to pelvic or paraortic lymph nodes
IVA Tumor invasion of bladder and/or bowel mucosa
IVB Distant metastasis including intra-abdominal or
inguinal node metastases
FIGURE 1 Secretory phase endometrium Irregular and often sinuous interdigitations of the endometrium with the myometrium are very common in both normal and neoplastic specimens.
Trang 3The distinction of inner-half invasion from
outer-half invasion is usually straightforward, and both the
probability of recurrence and likelihood of death
from tumor are markedly increased for women with
deeply invasive tumors However, there are 3
situa-tions in which the determination of maximal invasion
may be difficult In the first situation, lymphatic
invasion may be most easily recognized and
promi-nent in the myometrium deep to the invasive front of
the carcinoma The lymphatic channels containing
masses of neoplastic cells may be found in the
outer-half of the myometrium whereas the rest of the
neoplasm is confined to the inner-half of the uterus
In such cases, I believe it is most appropriate to
classify the tumor as a stage IB (inner-half
myoinva-sive) tumor and simply note the presence of
lymphatic invasion, which represents a separate poor prognostic factor In the second case, for a highly exophytic tumor, the location of the endometrial myometrial interface may be obscured by the presence of smooth muscle fibers that extend upward into the endometrium No rules have been proposed for determination of the depth of invasion in this situation, but Ali et al (6) have offered a few useful suggestions In such cases, I have arbitrarily esti-mated the depth of invasion based on the thickness of the myometrium in a portion of the fundus not affected by the neoplasm In the third situation, carcinoma is found confined to foci of adenomyosis
in the deep myometrium Several studies have demonstrated that this should not be considered a form of deep myoinvasion, as the outcome for these women is no worse than for those in whom tumor is absent from the adenomyosis (8,9)
HISTOLOGIC GRADE (GRADES 1, 2, AND 3) Stage I endometrial carcinomas are further sub-divided by histologic grade, reflecting the prognostic importance of tumor differentiation, particularly in early stage disease Although assignment of histologic grade is not particularly problematic currently, this largely reflects the significant clarification regarding histologic grading provided by pathologists during the past 2 decades In the early 1980s, the pathology committee of the GOG arbitrarily defined an architecturally based grading system for endometrial adenocarcinomas, using the percentage of the surface area in which there is glandular arrangement of the neoplasm (10) Grade I tumors are those in which less than 5% of the neoplasm is arranged as solid growth; grade 2 tumors are those in which 5% to 50% of the neoplasm is arranged in solid sheets; and grade 3 tumors are those in which greater than 50% of the neoplasm form solid masses Foci of squamous differentiation are not included in the assessment This system was later found to effectively discrimi-nate survival probability for women with clinically stage I and II endometrioid endometrial adenocarci-nomas, with 5-year survivals of 93% for women with grade 1 tumors, 85% for grade 2 tumors, and 69% for grade 3 tumors (11) Interestingly, it was later found useful not only in stratifying the overall survival for women with surgical stage I disease, with 5-year survival rates of 92%, 88%, and 75%, respectively, but also for those with metastatic (stage III) disease, with rates of 70%, 63%, and 40%
FIGURE 2 Interface of endometrial carcinoma with myometrium.
At low magnification (A), bundles of smooth muscle separate
neoplastic glands from one another At higher magnification (B),
it is more evident that this simply represents the interdigitations
of the basalis endometrium with myometrium, and a benign
endometrial gland is present in the middle of the field at the same
depth as the neoplastic glands.
Trang 4FIGO adopted this general schema for the 1988
system, but added the 3 provisos that follows: 1)
notable nuclear atypia, inappropriate for the
archi-tectural grade, raises the grade of a grade 1 or grade 2
tumor by 1; 2) in serous, clear cell and squamous cell
carcinoma, nuclear grading takes precedence; and 3)
adenocarcinomas with squamous differentiation are
graded according to the nuclear grade of the
glandular component (1) Notable nuclear atypia
was not precisely defined The first and third of these
provisos were subsequently addressed in studies by
the GOG Of 715 women with endometrioid
adeno-carcinomas, with or without squamous
differentia-tion, Zaino et al (12) found that upgrading was
prognostically justified only for those tumors in
which the majority of the neoplasm was composed
of cells with large, pleomorphic nuclei, coarse
chromatin, and large irregular nucleoli (Fig 3) A
lesser degree of nuclear atypia or severe but only focal
nuclear atypia was not associated with a significantly
diminished probability of survival With respect to
endometrioid adenocarcinomas with squamous
dif-ferentiation, the architectural differentiation of the
gland-forming portion of the tumors provided better
prognostic information than the nuclear grade of the
glandular or squamous component (12) Although
grading is prognostically important for endometrioid
adenocarcinoma and its subtypes, it has not been
found to be useful for serous, clear cell, or pure
squamous carcinomas Tumors of these cell types are associated with an aggressive behavior that does not seem to be influenced by architectural or nuclear features that have been studied to date Conse-quently, by convention, serous and clear cell carci-nomas of the endometrium are considered to be grade 3 Multiple prognostically useful alternative grading systems have been proposed during the past decade, based on either a 2-tiered or a 3-tiered division according to architectural grade, nuclear grade, or a combination of both (13–16) All of the systems display moderate to good reproducibility in limited investigations It is not clear whether any of the alternative systems would significantly improve the reproducibility, ease, or prognostic utility of the current method
STAGE II (CARCINOMAS THAT EXTEND INTO THE UTERINE CERVIX) Women with endometrial adenocarcinoma that spread to the cervix have a diminished probability
of survival compared with women whose tumors are confined to the uterine corpus, with FIGO results from 2003 indicating a 75% 5-year overall survival compared with about 88% for stage I tumors (7) However, tumors that spread to the cervix more often display other poor prognostic features, such as high grade, invasion of the outer-half of the myometrium, and lymphatic invasion, than do tumors confined to the corpus (17) In one study of 170 women with stage
II carcinoma, 58% had outer-half myoinvasion (versus 44% for stage I), 42% had capillary/ lymphatic space involvement, and 72% were grade
2 or 3 (versus 60% for stage I [18]) It is unclear whether involvement of the cervix is prognostically significant after adjustment for other poor-risk factors, but the effect of cervical spread in isolation seems to be a weak factor, if present
Stage II carcinomas are further divided into stage IIA (Fig 4A), which are those tumors in which carcinoma is confined to the endocervical glands, and stage IIB, which are those tumors in which carcinoma involves the cervical stroma (Fig 4B) FIGO has not provided any guidelines regarding the histologic definition or identification of carcinoma confined to glands, and different authors have considered it to represent surface epithelial involvement only, surface and underlying gland involvement, or mucosal spread (although no mucosa exists in the cervix) (8,19–22) Some of these definitions imply either a Pagetoid
FIGURE 3 Grade 3 endometrioid adenocarcinoma The majority
of this architectural grade 2 adenocarcinoma was composed of cells
with large, pleomorphic nuclei, coarse chromatin, and large
irregular nucleoli, justifying its upgrade to a International
Federation of Obstetricians and Gynecologists grade 3
endome-trioid adenocarcinoma Caution is justified, as many carcinomas
with extensive gland formation and high-grade nuclei actually
represent serous carcinoma.
Trang 5spread of neoplastic cells within the basement
membrane of the epithelium from a contiguous
primary tumor, or implantation and replacement of
denuded epithelium after curettage In practice, for
grade 1 endometrial tumors, it is often difficult to
determine whether the neoplastic glands in the cervix
represent preexisting or newly formed glands,
parti-cularly as a desmoplastic host response often is
absent in low-grade tumors In contrast, higher-grade
tumors have solid masses of neoplasm that infiltrate
the stroma and often provoke a desmoplastic
response Most tumors classified as stage IIA are
grade 1 Consequently, it is not surprising that
various studies have yielded conflicting data with
survival and recurrence rates for women with stage
IIB disease either worse or no different from those for
women with stage IIA disease (5,8,19–25) In most
studies, stage IIA disease is associated with the same prognosis as stage I tumors In summary, neither the prognostic importance nor the reproducibility of the diagnosis of stage II (and substages IIA and IIB) tumors has been rigorously evaluated, but reprodu-cibility seems to be poor and prognostic importance weak
STAGE IIIA (TUMOR INVADES UTERINE SEROSA, ADNEXA, OR POSITIVE PERITONEAL CYTOLOGY) Stage IIIA is extraordinarily heterogenous, as it includes those tumors that have not demonstrated spread beyond the uterus, those tumors which are present as isolated cells in peritoneal fluid but may not be capable of implantation, and those tumors with definite metastasis to other pelvic organs Between 3% and 30% of women with clinical stage
I or II endometrial carcinoma are found to have tumor cells in either ascitic fluid or in pelvic washing cytology, but only about 5% to 10% of women with
no extrauterine metastases identified pathologically have positive peritoneal cytology (26–35) Numerous studies have produced conflicting results regarding the significance of positive peritoneal fluid cytology
as a risk factor for tumor recurrence or survival in women with clinical stage I or II carcinoma In about half of the reports, it is associated with increased recurrence rates and decreased survival (28,32–34, 36–40), but in the other half, no difference was detected (28–32,34,35,39,41–43) Positive peritoneal fluid cytology is frequently associated with other high-risk factors such as high histologic grade, deep myome-trial invasion, and extrauterine disease The reported 5-year survival for those women with positive cytology but with no extrauterine metastases varies from about 80% to 90%, whereas the recurrence rate
is about 30% In a somewhat dated but excellent review of 17 studies and over 3,800 patients by Milosevic and colleagues in 1992 (33), they identified
5 studies in which multivariate analyses had been conducted that included grade and depth of invasion
in the models In the 3 larger studies, a malignant cytology was associated with a significant, indepen-dent decrease in survival or increase in the rate of recurrence, but its effect was less important than histologic grade In the 2 smaller studies, no such effect was found Recurrence in this group of patients
is typically as disseminated intraperitoneal carcino-matosis In about 5% of peritoneal fluid cytology
FIGURE 4 Cervical invasion by endometrial adenocarcinoma.
The distinction of cervical stromal invasion from endocervical
glandular involvement only can be difficult Although in some
areas, one might consider that his tumor could simply be involving
the cervical glands (A), in an adjacent field the invasion of the
stroma is evident (B).
Trang 6specimens, atypical cells are present that may
represent either reactive mesothelial cells or
low-grade adenocarcinoma In the absence of
immuno-histochemical stains that are absolutely specific and
sensitive, it is likely that this group that is indefinite
for stage IIIA cancer cannot be reduced further
Women whose tumors have spread to the adnexa
have a diminished survival compared with those
women without adnexal involvement Once again,
most of these women also have other adverse features
such as high grade, lymphatic invasion, deep
myo-metrial invasion, and other sites of extrauterine
disease Connell et al (44) reported a 5-year
disease-free survival of 37% for those with adnexal
spread, but it was 71% for those without other
extrauterine involvement The latter figure is close to
the mean disease-free survival of 79% taken from
a literature review for solitary adnexal involvement
(44) This data should be viewed with caution as
almost 5% of women with endometrial
adenocarci-noma are found to have carciadenocarci-noma in the ovary, and
many of these patients are believed to have separate
primary tumors, for whom the prognosis is excellent
(45) Until better ways are routinely employed to
distinguish synchronous primary tumors from
me-tastases, the impact of isolated ovarian or tubal
metastases will remain obscure
The third subgroup of stage IIIA consists of
women whose tumors have extended through the
myometrium to the uterine serosa It was found in
about 7% of women treated by primary surgery,
of whom half had extrauterine spread, and overall
carries a poor prognosis, with a 5-year disease-free
survival of about 30% in one study (46) As an
isolated finding in the absence of known metastasis
(a relatively uncommon event), the survival
in-creased, but was still poor at 41% at 5 years (46)
Mariani and colleagues (47) found a better 5-year
survival rate, but 83% of the tumors recurred in
extra-abdominal sites in that period of time
STAGE IIIB (TUMOR SPREAD
TO THE VAGINA) Although vaginal recurrences of endometrial
ade-nocarcinomas are relatively common, less than 1%
of patients present with vaginal metastasis in the
absence of spread to lymph nodes or distant sites
(48) More specifically, only about 2% to 3% of
women with stage III tumors are stage IIIB Such
tumors are biologically aggressive, with a reported
5-year survival of about 25% and a median sur-vival of only 1 to 2 years As the patients typically
do not have contiguous spread from uterine corpus
to cervix to vagina, it is likely that the tumor re-flects a lymphatic metastasis The sites of recurrent disease in this group of patients are quite variable, and include pelvis, lymph nodes, abdomen, and distant sites
STAGE IIIC (TUMOR METASTASIS TO PELVIC
OR PARA-AORTIC LYMPH NODES) About 10% of women with clinical stage I and II endometrial carcinoma are found at the time of surgico-pathologic staging to have metastasis to pelvic and/or para-aortic lymph nodes (49–51) After lymphadenectomy, radiation therapy is often directed
to the pelvis and nodal regions The probability of nodal spread is strongly related to risk factors, including cell type, histologic grade, depth of myometrial invasion, and lymphatic invasion (17) There is a relatively predictable pattern of spread of endometrial carcinoma to regional nodes, with the pelvic nodes involved first, followed by ascent to the para-aortic chain About one-third to one-half of women who have disease in the pelvic nodes also have spread to the para-aortic lymph nodes (17,49,50) Even this substage is quite heterogeneous Mariani and colleagues (52) reviewed 51 patients with stage IIIC disease Although the 5 years recurrence-free survival was 68% for women who had lymph nodes
as the only site of extrauterine disease, it dropped to 25% for those whose tumors also involved uterine serosa, adnexa, vagina, or peritoneal cytology (52) Relapses in the former group were largely confined to the node-bearing areas; whereas, the majority of the latter group had recurrences in other areas Similar but even more dramatic differences in survival between the 2 groups (93% versus 39%) were found
by McMeekin et al (53), who also noted that the depth of invasion in the uterus remained significant in
a multivariate analysis of survival Women with metastatic disease in the para-aortic lymph nodes have a much worse prognosis than those with spread only to the pelvic lymph nodes, with 5-year survivals of about 30% to 40% versus 70% to 80% (50,51,54) Further risk stratification is found accord-ing to the presence of residual nodal disease, divided
as occult, macroscopic resected, and macroscopic residual (49)
Trang 7GENERAL COMMENTS
AND A FEW NOTES
ON THERAPY
As one reviews the voluminous literature, it is evident
that the prognosis of endometrial adenocarcinoma is
related to a wide variety of features including those
intrinsic to the tumor (such as cell type and grade),
those related to its growth in the uterus (including the
depth of myometrial invasion and lymphatic
inva-sion), and those related to extrauterine spread As
noted previously, some of the features of the tumor in
the uterus still affect the prognosis for women with
metastatic tumor, and no single characteristic seems
to represent an overwhelmingly dominant prognostic
factor Thus, the prognosis, and sometimes
therapeu-tic decisions, for an individual patient often is based
on a constellation of features, rather than simply the
identification of the most advanced site of spread
This set of observations complicates the creation of
an optimal staging system
In the prior discussion, I have focused on prognostic
issues I will follow with a series of brief and
pro-vocative generalizations about the current limitations
or controversies regarding therapy Although 70%
to 80% of women with endometrial adenocarcinoma
are cured by surgery alone, disease beyond the uterus
remains a source of tremendous frustration, and
stag-ing systems should address the differences between
nodal disease, localized pelvic spread, peritoneal
carci-nomatosis, and extra-abdominal metastasis Patients
with high-risk, localized cancers treated with adjuvant
radiation to the pelvis or abdomen have lower rates of
pelvic recurrence, but are at equal risk for later distant
failure and seem to have no survival benefit Whole
abdominal radiation therapy is inferior to
chemother-apy for the treatment of women with maximally
debulked advanced endometrial adenocarcinoma
Several studies have suggested that lymphadenectomy,
in itself, may result in improved survival for women
with metastasis to pelvic and para-aortic lymph nodes
Targeted radiation therapy may be effective for the
treatment of localized vaginal recurrences, but neither
hormonal nor chemotherapy provides more than short
term and incomplete responses in most of the women
with distant or disseminated disease In summary,
therapy for advanced or recurrent endometrial
adeno-carcinoma remains suboptimal, with mean survival
measured in months to a few years, for most
situa-tions Further advances in treatment outcomes are
unlikely to result from conventional forms of
hormo-nal, radiation, or chemotherapy
A SUMMARY OF PROBLEMS AND SUGGESTIONS FOR REFINEMENT IN THE FIGO STAGING SYSTEM
1) Stage IA (tumors confined to the endometrium) cannot reliably be distinguished from stage IB (tumors invading the superficial myometrium) microscopically in many cases;
2) Stage IIA and IIB are poorly defined pathologi-cally and may not differ prognostipathologi-cally;
3) Stage II is probably not a statistically significant independent prognosticator of survival;
4) Stage III disease is very heterogeneous;
5) Stage IIIA alone is heterogeneous; isolated posi-tive peritoneal cytology alone is rare and probably significant but with small survival effect (85% 5-year survival); isolated adnexal spread is more significant (70% 5-year survival); uterine serosal involvement carries a poor prognosis (30% 5-year survival);
6) Stage IIIB (vaginal metastasis) is very rare and has a prognosis similar to stage IV tumors (25% 5-year survival);
7) Stage IIIC is heterogeneous, and patients who have nodal spread without other extrauterine spread have a significantly better prognosis (70%–90% 5-year survival) than those with both nodal and other extranodal disease (25%–40% 5-year survival);
8) Among women with stage IIIC disease, the prognosis for those with pelvic node metastasis
is significantly better (70%–80% 5-year survival) than for those with positive para-aortic nodes (30%–40% 5-year survival);
9) Among women with stage IIIC disease, the survival rates vary according to whether the nodes are grossly or microscopically positive (as assessed
by the operating surgeon), and whether the disease can be completely resected
Given the described problems in reproducibility, accuracy, and predictive value noted previously, and
to provoke further discussion, I would suggest that consideration be given to a staging system as shown
in Table 3 If we are to make further improvements in treatment and prognostication, it is time for pathol-ogists, gynecologic oncolpathol-ogists, radiation oncolpathol-ogists, and medical oncologists to engage in this conversa-tion together I look forward to the discussion that may follow
Trang 8Acknowledgments: The author thanks Drs Catherine
Abendroth and Timothy Leonard for their critical review
and Amanda Smith for her excellent assistance in the
preparation of this manuscript
REFERENCES
1 FIGO Announcements, stages-1988 Revision Gynecol Oncol
1989;35:125.
2 Kottmeier PH-L, ed Annual Report on the Results of
Treatment in Carcinoma of the Uterus, Vagina, and Ovary.
Stockholm: Radiumhemmet; 1971:2–18.
3 Cancer Committee Report to the General Assembly of FIGO.
Classification and staging of malignant tumor in the female
pelvis Int J Gynaecol Obstet: The Official Organ of the
International Federation of Gynaecology and Obstetrics 1971;9:
172–9.
4 Wolfson AH, Sightler SE, Markoe AM, et al The prognostic
significance of surgical staging for carcinoma of the
endome-trium Gynecol Oncol 1992;45:142–6.
5 Creasman WT, DeGeest K, DiSaia PJ, et al Significance of
true surgical pathologic staging: a Gynecologic Oncology
Group Study Am J Obstet Gynecol 1999;181:31–4.
6 Ali A, Black D, Soslow RA Difficulties in assessing the
depth of myometrial invasion in endometrial carcinoma Int
J Gynecol Pathol 2007;26:115–23.
7 Creasman WT, Odicino F, Maisonneuve P, et al Carcinoma of
the corpus uteri International Journal of Gynaecology and
Obstetrics: The Official Organ of the International Federation
of Gynaecology and Obstetrics 2003;83(suppl 1):79–118.
8 Clement PB, Young RH Endometrioid carcinoma of the
uterine corpus: a review of its pathology with emphasis on
recent advances and problematic aspects Adv Anat Pathol 2002;
9:145–84.
9 Jacques SM, Lawrence WD Endometrial adenocarcinoma
with variable-level myometrial involvement limited to
adeno-myosis: a clinicopathologic study of 23 cases Gynecol Oncol
1990;37:401–7.
10 Benda J, Zaino R GOG Pathology Manual NY: Buffalo; 1994.
11 Zaino RJ, Kurman R, Herbold D, et al The significance
of squamous differentiation in endometrial carcinoma Data from a Gynecologic Oncology Group study Cancer 1991;68: 2293–302.
12 Zaino RJ, Kurman RJ, Diana KL, et al The Utility of the Revised International Federation of Gynecology and Obste-trics Histologic Grading of Endometrial Adenocarcinoma Using a Defined Nuclear Grading System Cancer 1995; 75:81–6.
13 Alkushi A, Abdul-Rahman ZH, Lim P, et al Description of a novel system for grading of endometrial carcinoma and comparison with existing grading systems Am J Surg Pathol 2005;29:295–304.
14 Lax SF, Kurman RJ, Pizer ES, et al A binary architectural grading system for uterine endometrial endometrioid
carcino-ma has superior reproducibility compared with FIGO grading and identifies subsets of advance-stage tumors with favorable and unfavorable prognosis Am J Surg Pathol 2000;24:1201–8.
15 Scholten AN, Smit VT, Beerman H, et al Prognostic significance and interobserver variability of histologic grading systems for endometrial carcinoma Cancer 2004;100:764–72.
16 Taylor RR, Zeller J, Lieberman RW, et al An analysis of two versus three grades for endometrial carcinoma Gynecol Oncol 1999;74:3–6.
17 Morrow CP, Bundy BN, Kurman RJ, et al Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study Gynecol Oncol 1991;40: 55–65.
18 Pitson G, Colgan T, Levin W, et al Stage II endometrial carcinoma: prognostic factors and risk classification in 170 patients Int J Radiat Oncol, Biol, Phys 2002;53:862–7.
19 Eltabbakh GH, Moore AD Survival of women with surgical stage II endometrial cancer Gynecol Oncol 1999;74:80–5.
20 Fanning J, Alvarez PM, Tsukada Y, et al Prognostic significance of the extent of cervical involvement by endome-trial cancer Gynecol Oncol 1991;40:46–7.
21 Jordan LB, Al-Nafussi A Clinicopathological study of the pattern and significance of cervical involvement in cases of endo-metrial adenocarcinoma Int J Gynecol Cancer 2002;12:42–8.
22 Prat J Prognostic parameters of endometrial carcinoma Hum Pathol 2004;35:649–62.
23 Ayhan A, Taskiran C, Celik C, et al The long-term survival of women with surgical stage II endometrioid type endometrial cancer Gynecol Oncol 2004;93:9–13.
24 Blake P, Lodge N, A’Hern RP An audit of outcome of adjuvant post-operative radiotherapy for 52 women with stage
II carcinoma of the endometrium Br J Radiol 2000;73:987–93.
25 Jobsen JJ, Schutter EM, Meerwaldt JH, et al Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma Int J Gynecol Cancer 2001;11:49–53.
26 Creasman WT, Disaia PJ, Blessing J, et al Prognostic significance of peritoneal cytology in patients with endometrial cancer and preliminary data concerning therapy with intra-peritoneal radiopharmaceuticals Am J Obstet Gynecol 1981; 141:921–9.
27 Grimshaw RN, Tupper WC, Fraser RC, et al Prognostic value
of peritoneal cytology in endometrial carcinoma Gynecol Oncol 1990;36:97–100.
28 Harouny VR, Sutton GP, Clark SA, et al The importance of peritoneal cytology in endometrial carcinoma Obstet Gynecol 1988;72:394–8.
29 Kadar N, Homesley HD, Malfetano JH Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease Gynecol Oncol 1992;46:145–9.
30 Kennedy AW, Peterson GL, Becker SN, et al Experience with pelvic washings in stage I and II endometrial carcinoma Gynecol Oncol 1987;28:50–60.
TABLE 3 A proposal for a revised staging system for
tumors of the uterine corpus
Stage Characteristics
IA G123 Invasion to endometrium/inner-half of myometrium
IB G123 Invasion to outer-half of myometrium
IIA Positive peritoneal cytology
IIB Uterine serosa, adnexal, or other pelvic spread
IIIA1 Pelvic nodal metastasis only (microscopic)
IIIA2 Pelvic nodal metastasis only (gross* )
IIIB1 Para-aortic nodal ( 7pelvic nodal) metastasis only
(microscopic)
IIIB2 Para-aortic nodal ( 7pelvic nodal) metastasis only
(gross* )
IIIC Pelvic or para-aortic nodal metastasis with other
extrauterine spread
IVA Vaginal metastases, invasion of bladder or bowel
mucosa
IVB Distant metastasis including intraabdominal or
inguinal node metastases
* The assessment of gross involvement of lymph nodes by
metastatic tumor is made by the operating surgeon.
Trang 931 Konski A, Poulter C, Keys H, et al Absence of
progno-stic significance, peritoneal dissemination and treatment
advantage in endometrial cancer patients with positive
peritoneal cytology Int J Radiat Oncol, Biol, Phys 1988;14:
49–55.
32 McLellan R, Dillon MB, Currie JL, et al Peritoneal cytology
in endometrial cancer: a review Obstet Gynecol Survey
1989;44:711–9.
33 Milosevic MF, Dembo AJ, Thomas GM The clinical
significance of malignant peritoneal cytology in stage I
endometrial carcinoma Int J Gynecol Cancer 1992;2:225–35.
34 Obermair A, Geramou M, Tripcony L, et al Peritoneal
cytology: impact on disease-free survival in clinical stage I
endometrioid adenocarcinoma of the uterus Cancer Lett 2001;
164:105–10.
35 Yazigi R, Piver MS, Blumenson L Malignant peritoneal
cytology as prognostic indicator in stage I endometrial cancer.
Obstet Gynecol 1983;62:359–62.
36 Brewington KC, Hughes RR, Coleman S Peritoneal cytology
as a prognostic indicator in endometrial carcinoma J Reprod
Med 1989;34:824–6.
37 Imachi M, Tsukamoto N, Matsuyama T, et al Peritoneal
cytology in patients with endometrial carcinoma Gynecol
Oncol 1988;30:76–86.
38 Mazurka JL, Krepart GV, Lotocki RJ Prognostic significance
of positive peritoneal cytology in endometrial carcinoma Am
J Obstet Gynecol 1988;158:303–6.
39 Santala M, Talvensaari-Mattila A, Kauppila A Peritoneal
cytology and preoperative serum CA 125 level are important
prognostic indicators of overall survival in advanced
endome-trial cancer Anticancer Res 2003;23:3097–103.
40 Turner DA, Gershenson DM, Atkinson N, et al The
prognostic significance of peritoneal cytology for stage I
endometrial cancer Obstet Gynecol 1989;74:775–80.
41 Fadare O, Mariappan MR, Hileeto D, et al Upstaging based
solely on positive peritoneal washing does not affect outcome
in endometrial cancer Mod Pathol 2005;18:673–80.
42 Hirai Y, Fujimoto I, Yamauchi K, et al Peritoneal fluid
cytology and prognosis in patients with endometrial
carcino-ma Obstet Gynecol 1989;73:335–8.
43 Tebeu PM, Popowski Y, Verkooijen HM, et al Positive peritoneal cytology in early-stage endometrial cancer does not influence prognosis Br J Cancer 2004;91:720–4.
44 Connell PP, Rotmensch J, Waggoner S, et al The significance
of adnexal involvement in endometrial carcinoma Gynecol Oncol 1999;74:74–9.
45 Zaino R, Whitney C, Brady MF, et al Simultaneously detected endometrial and ovarian carcinomas—a prospective clinico-pathologic study of 74 cases: a gynecologic oncology group study Gynecol Oncol 2001;83:355–62.
46 Ashman JB, Connell PP, Yamada D, et al Outcome of endometrial carcinoma patients with involvement of the uterine serosa Gynecol Oncol 2001;82:338–43.
47 Mariani A, Webb MJ, Keeney GL, et al Assessment of prognostic factors in stage IIIA endometrial cancer Gynecol Oncol 2002;86:38–44.
48 Nicklin JL, Petersen RW Stage 3B adenocarcinoma of the endometrium: a clinicopathologic study Gynecol Oncol 2000; 78:203–7.
49 Bristow RE, Zahurak ML, Alexander CJ, et al FIGO stage IIIC endometrial carcinoma: resection of macroscopic nodal disease and other determinants of survival Int J Gynecol Cancer 2003;13:664–72.
50 Hirahatake K, Hareyama H, Sakuragi N, et al A clinical and pathologic study on para-aortic lymph node metastasis in endometrial carcinoma J Surg Oncol 1997;65:82–7.
51 Nelson G, Randall M, Sutton G, et al FIGO stage IIIC endometrial carcinoma with metastases confined to pelvic lymph nodes: analysis of treatment outcomes, prognostic variables, and failure patterns following adjuvant radiation therapy Gynecol Oncol 1999;75:211–4.
52 Mariani A, Webb MJ, Keeney GL, et al Stage IIIC endometrioid corpus cancer includes distinct subgroups Gynecol Oncol 2002;87:112–7.
53 McMeekin DS, Lashbrook D, Gold M, et al Analysis of FIGO Stage IIIc endometrial cancer patients Gynecol Oncol 2001;81:273–8.
54 Corn BW, Lanciano RM, Greven KM, et al Endometrial cancer with para-aortic adenopathy: patterns of failure and oppor-tunities for cure Int J Radiat Oncol, Biol, Phys 1992;24:223–7.