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Dysfunctional Uterine Bleeding
Dysfunctional uterine bleeding (DUB)
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Clinically, DUB indicates ovulatory dysfunction.By definition, DUB excludes postmenopausal bleeding or bleeding caused by the presence of specific pathologic processes such as inflammation, polyps, hyperplasia, carcinoma, exogenous hormones, and complications of pregnancy.
It is important to recognize the endometrial changes associated with DUB, because they may be confused with more serious lesions such as hyperplasia.
Morphologic Features of Glandular and Stromal Breakdown
as it commonly occurs with dysfunctional bleeding, especially anovulatory cycles. Regardless of the extent of the morphologic changes, abnormal glandular and stromal breakdown usually does not occur uniformly throughout the uterine cavity. As a result, abnormal bleeding typically leads to a heterogeneous pattern with fragments of intact, nonshedding endometrium admixed with endometrium showing the morphologic changes of abnormal bleeding.
Menstrual endometrium also shows breakdown, but the changes affect all the tissue and occur on a background of late secretory phase glands.Furthermore, in menstrual endometrium the breakdown is acute and lacks the changes of chronic bleeding, such as hemosiderin deposition, eosinophilic syncytial
change, or foam cell accumulation, seen in abnormal bleeding patterns.
Features of endometrial breakdown and bleeding.
1 Stromal “collapse”
2 Stromal cell clusters
3 Fibrin thrombi
4 Nuclear debris at base of gland cells
5 Nuclear debris in stroma
6 Eosinophilic syncytial change
7 Hemosiderin
8 Foam cells
9 Stromal fibrosis and hyalinization
Estrogen-Related Bleeding
When proliferative endometrium shows breakdown and bleeding, the pattern strongly
suggests anovulatory cycles. Exogenous estrogens can cause similar patterns, and therefore a complete clinical history is needed to be certain that the bleeding pattern is truly due to anovulation. The differential diagnosis of proliferative phase endometrium with glandular and stromal breakdown also includes inflammation, polyps, and leiomyomas.
Disordered Proliferative Phase and Persistent Proliferative Phase
Sometimes more sustained estrogen stimulation may result in the focal branching and some dilation of glands, yielding a proliferative phase pattern that is neither normal nor hyperplastic.
The terms“disordered proliferative phase pattern” and “persistent proliferative phase”
have been applied to describe this pattern of proliferative endometrium with tortuous and mildly disorganized glands. In our experience, “disordered proliferative” often is inappropriately applied to a variety of patterns, including normal proliferative endometrium, proliferative endometrium with breakdown, artifactual crowding, basalis, and simple hyperplasia.
The diagnosis of disordered proliferative phase should be reserved for cases in which
assessment is based on intact, welloriented fragments of tissue. In these areas the
abnormal glands should be focal.These glands are qualitatively similar to those seen in
simple hyperplasia, but they are limited in extent and interspersed among glands with a
normal proliferative phase pattern.This criterion helps to separate the focal disordered
proliferative phase pattern from simple hyperplasia, a more diffuse abnormality.If the
tissue is extensively fragmented or disrupted by the procedure and contains mainly
detached proliferative glands, it is best to diagnose the change only as proliferative.
Extensive breakdown in proliferative endometrium can also display a disorganized
appearance to the glands because of fragmentation, but again this change is not that of a
true disordered proliferative phase pattern.
Atrophy
The epithelium is low columnar to cuboidal with small, dark nuclei and minimal cytoplasm. Stroma is scant or absent, consisting of a few clusters of small spindle cells. Mitotic activity is absent.
Biopsy specimens from reproductive-age and perimenopausal women occasionally show
abnormal secretory phase patterns with associated nonmenstrual breakdown and bleeding. In
such cases the pattern is secretory owing to ovarian progesterone production, but the
glandular and stromal changes usually are less advanced than those seen in normal late
secretory endometrium.The endometrial pattern does not correlate with any date of the
normal luteal phase. The glands may show secretory changes yet lack marked tortuosity
and secretory exhaustion, while the stroma lacks extensive predecidual change.In other
cases the glands appear to show a “hypersecretory” pattern, with vacuolated cytoplasm,
marked tortuosity, and luminal secretion, while the stroma lacks predecidual change. In
addition, the tissue shows foci of breakdown with characteristic changes such as nuclear
dust, fibrin thrombi, and dense cell clusters, similar to that which occurs in the
proliferative endometrium with glandular and stromal breakdown . Often in abnormal
secretory bleeding patterns, the glands show stellate shapes as they involute . This
latter pattern of collapsing, star-shaped secretory glands is nonspecific, however, and
simply shows secretory gland regression that could be due to a variety of factors.
When a pattern of nonmenstrual phase secretory endometrium with breakdown is present,
the abnormality may be due to defined or undefined luteal phase abnormalities or other
causes that are not evident from the sections.
Luteal Phase Defects
Irregular Shedding
Abnormal Secretory Endometrium with Breakdown of Unknown Etiology
Clinical Queries and Reporting
When a biopsy is performed for DUB, the report should address the presence or absence
of morphologic changes of breakdown and bleeding as well as any specific lesions.
If the pattern is that of proliferative endometrium with breakdown and if the clinical
history is appropriate, the changes can accurately be attributed to anovulatory cycles.
A descriptive diagnosis such as “proliferative endometrium with glandular and stromal
breakdown” offers a precise morphologic interpretation of the anovulatory bleeding
pattern that often is sufficient for clinical management.
If the changes show nonmenstrual secretory endometrium with breakdown but these are not
diagnostic of a defined luteal phase abnormality, descriptive terms such as “abnormal
secretory phase pattern with breakdown” communicate the observation of an abnormal yet
benign appearance while not assigning definite morphologic etiology.
Because atrophy is one of the most frequent causes of abnormal bleeding in postmenopausal
patients, it is important to recognize the morphologic features of atrophy and correctly
report the findings. A scant amount of endometrium consisting of detached strips of
atrophic endometrial epithelium with little stroma should be regarded as consistent with
atrophy and not “insufficient for diagnosis.” A brief comment or description of the
findings helps the clinician understand the basis of the diagnosis while providing
reassurance that the endometrium has, in fact, been sampled.
Unless the breakdown is clearly menstrual,i.e., reflecting the shedding at the end of a
normal ovulatory cycle, breakdown patterns should not be diagnosed as “menstrual.”
Instead, it is better to use descriptive diagnoses that reflect the morphologic changes.
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