(Module I)
EIN Overview

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. 

***Hot Tips***

Koch's Postulates for endometrial Precancers?

Koch developed 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

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Endometrial Intraepithelial Neoplasia, EIN, is the histopathologic presentation of 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

(anovulatory, or disordered proliferative)

Estrogen Effect

Hormonal therapy



Focal progressing to diffuse


Hormonal or surgical


Focal progressing to diffuse



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WHY use EIN?

EIN is a user-friendly clinically relevant diagnostic system that fits the scientific facts

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 information.  

Problems with the status quo, the WHO Hyperplasia system:

  1. Poor diagnostic reproducibility, especially of presence or absence of cytologic atypia.

  2. Fixed concept of cytologic "atypia" does not accomodate changes in cytology caused by ambient hormonal state.

  3. Objective architectural criteria ("simple" vs. "complex") for precancer diagnosis are unspecified. 

  4. 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.

  5. No accomodation for focal origin of neoplastic clones, or consideration of increasing disease burden (lesion size) with progression. 


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How Does EIN Correlate with WHO Hyperplasias?

Figure 1: 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)

***Hot Tips***

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 Click Here




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Copyright 1998-2015 by George L. Mutter, MD.  All Rights Reserved