(Module II) 
EIN Cytology
"Cytologic Demarcation" of EIN Lesions

There is no absolute standard for cytologic features of EIN lesions, but the cytology of EIN is usually clearly demarcated as divergent from that of co-existing benign endometrial tissues in the same patient. Stereotypical static descriptions of cytologic atypia, such as nuclear rounding and appearance of nucleoli are met in many but not all EIN lesions.  In this sense, a fixed presentation of cytologic atypia is not a prerequisite for EIN.    

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Cytologic Demarcation: Altered cytology relative to benign endometrial source tissues, Cytologic Demarcation,  is a second criterion for EIN diagnosis.  This is quite contrary to the WHO hyperplasia classification schema which focused heavily upon a fixed image of  "atypia" as the major determinant of  cancer risk.   In practice, identification of "atypia" is poorly reproducible between pathologists, and attempts to define an absolute standard are confounded by the extreme morphologic plasticity of endometrial glandular cells under changing hormonal, repair, and differentiation conditions.  In those cases with no normal glands for internal reference, it is necessary to assess the freestanding cytology of relevant fragments in the context of their architectural features.  Some EIN lesions occupy the entire tissue sample, and should not be underdiagnosed for lack of a convenient benign gland in the area.

PTEN immunohistochemistry of premalignant lesions defective in expression of this tumor suppressor gene shows precise demarcation of neoplastic glands (pale green) from non-neoplastic glands (brown).  Cytologic demarcation is evident in these paired H&E/immunohistochemical  views.

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Go to More Examples of  Cytologic Demarcation   
Go to Examples of classic Atypical, Controversial, and Non-Atypical Cytology

PTEN: Cytologic demarcation between neoplastic and non-neoplastic glands develops in EIN lesions, but may be absent for earlier phases of tumorigenesis detected by PTEN immunohistochemistry in otherwise unremarkable normal proliferative endometrium, for example. For this reason, cytologic demarcation is a late, rather than early, change associated with evolution of transformed premalignant clones.   Additional information is at PTEN Central, which reviews informativeness and Appropriate Use of this biomarker in a variety of endometrial tissues, and morphologic changes of progression.  

    The manner of cytologic change in EIN varies considerably from patient to patient, and can include but not be limited to, increased variation in nuclear size and contour,  clumped or granular chromatin texture, change in nucleoli, change in nuclear/cytoplasmic ratio, and altered cytoplasmic differentiation.   Beware diagnosing an EIN lesion if the cytology is identical between areas with crowded compared to uncrowded glands!  Many of these are artifactual disruptions where the stroma is sheared and glands pushed in apposition.  

    Many EIN lesions must be diagnosed without the benefit of comparison with companion benign tissues, either  because the sample is scanty or entirely comprised of EIN.   Exclusion of artifact and careful evaluation of the architecture usually permits accurate diagnosis in these instances.  

After reading this page see examples by clicking on the left guidebar.

Problems with Differentiation state: Cytologic demarcation criteria are easiest to apply to glandular endometrioid epithelium, and caution must be applied in dealing with non-endometrioid differentiation.

Squamous morules (below) are often associated with EIN, in which case cytologic evaluation should be confined to the glandular epithelium.

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Tubal change (below) can be seen in benign endometria exposed to protracted estrogen.

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Reactive changes seen in inflammatory conditions such as pyometrium (left below) or degenerative papillary change with mucin droplets (right below) are not true "metaplasias", but rather mimics.

  React in Pyometria.jpg (95114 bytes) ReactMucinDrop.jpg (72328 bytes)


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