(Module II)
EIN Exclusion Criteria

or, Things to exclude before considering an EIN Diagnosis

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Exclude Mimics - Benign and Malignant

Patients with one of the conditions listed below may still have an EIN, but this diagnosis should be made with careful consideration into how the coexisting factor(s) may modify the positive architectural and cytologic criteria for EIN diagnosis.  

If a specimen is refractory to confident diagnosis, a comment as to the nature of the problem may be useful in determining management.  For example, a scanty sample can be met with rebiopsy, or the confusing effects of progesterone obviated by allowing the patient to undergo a withdrawal bleed and subsequent rebiopsy while off exogenous hormones. See Tips for Ambiguous Lesions.

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Benign Mimics to Exclude

Artifacts and sampling problems like the telescoping artifact seen below.: 

Telescoping.jpg (100293 bytes)

Reactive changes: may be caused by infection, physical disruption, recent pregnancy, or recent instrumentation. 

React in Pyometria.jpg (95114 bytes) React.jpg (73494 bytes) ReactMucinDrop.jpg (72328 bytes)SurfaceReact.jpg (93026 bytes)

Menstrual endometrium: is one of the most common benign endometria overdiagnosed as a precancer or cancer.  Breakdown may follow an ovulatory cycle (far left), after anovulation (left center, with fibrin thrombi), and persist into the transitional period between late menses and early proliferative endometrium (right center).  Altered cytology is due to piling up of epithelial cells unsupported by stroma, and associated nuclear changes such as loss of polarity which may be accentuated under certain fixation conditions (right, Bouin's fixed). 

ME.jpg (109121 bytes) ME with thrombi.jpg (99315 bytes) Early.jpg (97398 bytes) MenstrualAtypia.jpg (91584 bytes)  

Polyps :contain irregularly spaced glands whose cytology may differ from native endometrium due to their tendency to have reduced hormonal responsiveness.

EMP.jpg (76318 bytes) EMP1.jpg (71805 bytes)

***Hot Tips***

EIN may present within a polyp, and should be diagnosed as EIN.
Apply all inclusive EIN criteria using the background polyp as a reference point, not the native functionalis.  Be aware that individual EIN criteria may be seen within benign polyps.

For examples,   Click Here

Normal late secretory endometrium displays loss of nuclear polarity, nuclear enlargement, and variation in nuclear size which if measured objectively by computerized morphometry overlaps substantially with EIN lesions.  Stromal responsiveness to progesterone is not homogenous at all endometrial depths.  Lack of stromal pre-decidualization in the deeper functionalis and superficial basalis makes glands appear crowded, and these same glands may display a worrisome cytology and complicated saw-toothed luminal profile.

 SEb-large.jpg (67248 bytes)

Hormone exposure: alters endometrial cytology, and architecture. Progesterone exposure may make a bona fide EIN hard to recognize, and a perfectly benign endometrium acquire the crowded architecture and "atypical" cytology of EIN.  In its most extreme form, pregnant patients with Arias Stella phenomenon (left) have dramatic epithelial atypia caused by polyploidy, and these areas typically demonstrate minimal stromal decidualization, resulting in very crowded gland architecture. This contrasts to the extreme decidualization and glandular exhaustion caused by the Pill (right) 

AriasStella.jpg (74208 bytes) Pill.jpg (77695 bytes)

Premalignant lesions exposed to progesterone tend to display nuclear shrinkage and homogenization of coarse chromatin, with pseudodecidual change responsible for expansion of stromal volume and separation of glands to make them appear less crowded.  This is apparent in the example below of an index EIN lesion with squamous morules (left, untreated) seen after six months of high dose progesterone therapy (right).  Morules generally do not contain progesterone receptors, and have persisted in this patient to indicate the site of previous EIN lesion.  Note the cytology of associated glands pre-and post progesterone. . 

EINpre-Prog.jpg (68991 bytes) EIN6moProg.jpg (75967 bytes)

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Exclude Cancer
Cancer may coexist with EIN in an individual patient, but should be always be separately diagnosed as it must be surgically, not hormonally, ablated. Keep in mind that absence of carcinoma in a tissue biopsy does not exclude the possibility of that the patient has a cancer which was unsampled during the biopsy procedure. An opinion should always be rendered based upon available material, and clearly stated.

Carcinoma : Any of the following features may be present in carcinoma but none are characteristic of EIN. Illustrated from left to right by a series of endometrial carcinomas are: 1)Rambling or mazelike interconnected gland lumens; 2)significant cribriform growth pattern; 3)solid areas of neoplastic, non-squamous, epithelium, 4)Bizarre or high grade nuclei, or 5)myometrial invasion (not illustrated, rarely seen in a biopsy).


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