Objective: Type collections
promote standardized classification by extrapolation from thoroughly documented examples.
This grouping presents premalignant and benign endometrial tissues, along with
results from multidisciplinary studies which were
used as the basis for classification (Click here for a
quick example). None of the individual analytical methods applied are
infallible, nor do all precancers have the same structural and genetic presentation.
In the past this created confusion which remained unresolved through lack of a verifiable
standard. The forum of this Website provides an opportunity to make directly available in
one place a comprehensive report of raw data that might otherwise have been split
into fragments or never shown in raw form. It provides a tool for pathologists,
researchers, and health care practicioners to integrate molecular genetic information with
histopathology and thereby more closely approach a true standard. Examples can be browsed in sequence or retrieved by
query.The Project: When the first confirmed monoclonal
putative endometrial precancers were circulated in the Div. of Women's and Perinatal
Pathology at Brigham and Women's Hospital it quickly became apparent that diagnostic
opinions, and styles of individual pathologists, were sufficiently variable that a true
concensus could be obtained only in a subset of cases. We responded by expanding
our repertoire of monoclonal precancers, intermingling them with otherwise benign
endometrium, and circulating them amongst a group of pathologists for formal
readings. The first group of reviewers included four gynecologic pathologists:
myself and Chris Crum of Brigham and Women's Hospital, Alex Ferenczy of the Sir Mortimer
Davis Hospital in Montreal, and Ralph Richart of Columbia Presbyterian Medical Center in
New York. A total of 93 non-malignant endometrial areas in histological slides from
hysterectomies of 64 women with endometrial adenocarcinoma provided DNA for genetic
analysis (isolated from adjacent sections). The source tissues were delineated by
circling in ink on the coverslip to ensure all pathologists were interpreting the same
areas. Summaries of diagnoses
by clonal composition can bee seen in graphic form.
We next tried to reduce subjective variation in histologic diagnosis through
application of objective morphometry. All slides were then subjected to Computerized
Morphometric Analysis by Dr. Jan P. A. Baak of the Free University of Amsterdam, and
Alkmaar Hospital, Alkmaar, The Netherlands. The D-Score was highly predictive of
clonal composition, and much more reproducible than the opinion of pathologists.
Overall, the Computerized D-Score correlated very well with
pathologist classification.
The Bottom Line: Diagnosis of endometrial precancers requires
consideration of several potentially confounding (polyps, progestin effects) or
superceding (carcinoma) entities by a skilled pathologist. After such exclusion, a
concensus approach was used to classify lesions as precancers or non-precancers based upon
concordance results of at least two of three analytical methods: Clonal analysis, Average
of four Pathologist Diagnoses, and Computerized Morphometric Analysis. We
found no basis for rational and reproducible subdivision of precancers, and thus suggest
that all be placed in a singular group designated Endometrial
Intraepithelial Neoplasia.
Many atypical endometrial hyperplasias, and some non-atypical
hyperplasias are precancers that can be diagnosed as EIN lesions using
revised criteria. Endometria with equivocal cytology may be split into precancer and
non-precancer groups using architectural features. The most predictive architectural
feature is a component of the D-Score, Volume Percentage Stroma. Of all measured
parameters used to calculate the D-Score, VPS was most predictive of monoclonal
composition when less than 55% of the total sample volume. VPS
correlates remarkably well with pathologist diagnoses and may be estimated with manual
methods such as a simple ocular grid. Manual assessment of VPS is suggested as an
informative element in discrimination between high and low risk lesions with bland
cytology.
We invite you to Explore the Type Collection.
