New data in the last 5 years has completely
revamped the scientific underpinnings of the manner in which premalignant
endometrial disease is defined and diagnosed. EIN is the histopathologic
presentation of premalignant endometrial disease. It is not just a renaming of
an old diagnostic entity, but is based upon a new
clonal model of premalignant disease, fulfilling a
series of precancer postulates, and
implementation of recently defined diagnostic criteria.
Koch's Postulates for endometrial
a series of criteria, or postulates, that must be fulfilled in order
to scientifically prove pathogenesis of disease by a specific
infectious organism. Similarly, it is possible to make
fundamental predictions about the characteristics of precancers that
would establish their relationship to subsequent malignancies.
There is now sufficient data to fulfill precancer postulate
requirements for EIN.
To see a precancer postulates,
and how they are met by EIN, Click Here
WHAT is EIN?
Endometrial Intraepithelial Neoplasia, EIN, is the histopathologic
premalignant endometrial disease which confers an elevated risk for endometrial
cancer. The singular category of EIN is not stratified or divided
into subgroups, and must be distinguished from earlier phases of latent
premalignant disease, and endometrial carcinoma.
Table I: EIN Terminology and Diagnostic Criteria
EIN needs to be treated, and the type of therapy decided between
the patient and treating physician. Things that may influence the
choice of surgical vs. hormonal therapy include but are not limited to:
diagnostic confidence that a co-existing carcinoma has been excluded, desire for
maintained fertility, ability to perform followup surveillence, and
patient-specific hormonal and surgical risks.
Proliferative endometrium with alterations in architecture consistent
with unopposed estrogen effect
or disordered proliferative)
Focal progressing to
Hormonal or surgical
Focal progressing to diffuse
WHY use EIN?
EIN is a user-friendly clinically relevant diagnostic system that fits the
Clinical Relevance: was
a priority of the 19 gynecologic pathologists who proposed EIN as a diagnostic
term after critically reviewing clinical needs and new scientific
Problems with the status quo, the WHO
Poor diagnostic reproducibility, especially of presence or absence of cytologic
Fixed concept of cytologic "atypia" does not
accomodate changes in cytology caused by ambient hormonal state.
Objective architectural criteria ("simple" vs.
precancer diagnosis are unspecified.
The number of diagnostic categories varies greatly, based
upon permutations of cytologic and architectural classification.
Modifications of the four classes
originally defined by presence or absence of cytologic atypia
(atypical/non-atypical), and a complex or simple architecture are commonplace. Simplifications
yield three groups by combining all architectures into one class of atypical
lesions (atypical endometrial hyperplasias may be complex or simple). In
contrast, the architecture and cytology have each been graded by some
practitioners into three "grades" of mild, moderate and severe,
effectively resulting in a 3x3, or 9-part classification.
No accomodation for focal origin of neoplastic clones, or
consideration of increasing disease burden (lesion size) with
How Does EIN Correlate with WHO
Because EIN lesions are diagnosed using different criteria than WHO
hyperplasias, the correlation is not fixed. Colored
portions of Bar
Graphs show approximate percentages of each WHO hyperplasia class that will be
diagnosed as EIN using criteria in Table II below.
Remaining WHO hyperplasias not diagnostic of EIN (gray) will be
allocated to unopposed estrogen (anovulatory), polyp, and other benign
categories. Pie chart shows
relative contributions of each hyperplasia type to the EIN diagnostic category
in a biopsy series of sequential endometrial hyperplasias seen in a busy
hospital practice. Examples
of rediagnosed cases are available.
(Data from Hecht and Mutter, 2004)
Surprised by the concordance of
WHO hyperplasia with EIN diagnoses? Assignment of
hyperplasia diagnoses varies dramatically between pathologists.
"Complex non-atypical hyperplasia," for example, can either be a very
common or rarely invoked diagnosis. This has a substantial
impact on how your prior practice patterns will relate to more
standardized EIN groups.
Our concordance graphic is based
upon combined experience of multiple European and American groups, and
thus shows general trends.
To see a series of examples