International Journal of Medical Science and Public Health Research
01
https://ijmsphr.com/index.php/ijmsphr
TYPE
Original Research
PAGE NO.
01-06
OPEN ACCESS
SUBMITED
03 April 2025
ACCEPTED
02 May 2025
PUBLISHED
01 June 2025
VOLUME
Vol.06 Issue06 2025
COPYRIGHT
© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.
Clinicopathological
Correlation of Abnormal
Uterine Bleeding Patterns
with Endometrial
Histopathology
Dr. Monica R. Malik
Professor, Department of Obstetrics and Gynecology, All India Institute of
Medical Sciences (AIIMS), New Delhi, India
Dr. Ritu Singh
Professor, Department of Obstetrics and Gynecology, King George’s
Medical University, Lucknow, India
Abstract:
Abnormal Uterine Bleeding (AUB) is a
common gynecological complaint affecting women
across various age groups, significantly impacting their
quality of life. The diverse etiologies of AUB necessitate
a thorough investigation to identify underlying
pathologies,
particularly
those
involving
the
endometrium. This study aims to establish a
clinicopathological correlation between different
patterns of abnormal uterine bleeding and findings from
endometrial histopathology. By analyzing a cohort of
patients presenting with AUB, this research will
categorize bleeding patterns based on clinical history
(e.g., menorrhagia, metrorrhagia, postmenopausal
bleeding) and subsequently correlate these patterns
with specific histological diagnoses obtained from
endometrial biopsies or curettage samples. The study
will assess the prevalence of various endometrial
pathologies, such as endometrial hyperplasia (simple,
complex, atypical), endometrial polyps, endometritis,
carcinoma, and hormonal imbalances, across different
AUB presentations. Furthermore, it will investigate the
diagnostic utility of endometrial sampling in
distinguishing
between
benign
and
malignant
conditions in patients with AUB. The findings of this
clinicopathological correlation will provide valuable
insights for clinicians in the effective diagnosis,
management, and prognostication of patients
presenting with abnormal uterine bleeding, thereby
optimizing patient care and minimizing unnecessary
invasive procedures.
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Keywords:
Abnormal Uterine Bleeding (AUB),
Endometrial
Histopathology,
Clinicopathological
Correlation,
Endometrial
Biopsy,
Endometrial
Hyperplasia, Endometrial Carcinoma, Menorrhagia,
Metrorrhagia, Postmenopausal Bleeding, Uterine
Pathology, Gynecology.
Introduction:
Abnormal Uterine Bleeding (AUB) is a
common gynecological complaint that significantly
impacts a woman's quality of life, affecting physical,
emotional, and social well-being [1, 2]. It is defined as
any deviation from the normal menstrual cycle in
terms of regularity, frequency, duration, or volume of
bleeding [1]. AUB can manifest in various ways,
including heavy menstrual bleeding, intermenstrual
bleeding, prolonged bleeding, or irregular bleeding,
and can occur across a woman's reproductive lifespan,
from adolescence through perimenopause and into
postmenopause [3, 7, 8, 13]. The underlying causes of
AUB are diverse, ranging from benign conditions to
potentially life-threatening malignancies, necessitating
a thorough diagnostic approach for effective
management [4, 5, 6, 9, 10, 11, 12].
The International Federation of Gynecology and
Obstetrics (FIGO) developed the PALM-COEIN
classification system in 2011 to standardize the
nomenclature and etiology of AUB, facilitating clearer
communication and more consistent diagnosis and
treatment strategies [1]. This classification divides the
causes into structural (PALM: Polyp, Adenomyosis,
Leiomyoma, Malignancy and hyperplasia) and non-
structural
(COEIN:
Coagulopathy,
Ovulatory
dysfunction, Endometrial, Iatrogenic, Not yet
classified) categories [1]. While clinical evaluation
provides initial clues, a definitive diagnosis often relies
on histopathological examination of endometrial
tissue [2, 4, 5, 6, 9, 10, 11, 12]. Endometrial biopsy or
curettage remains a cornerstone in the diagnostic
workup of AUB, particularly in women over 40 years of
age or those with risk factors for endometrial
pathology, as it allows for the identification of specific
underlying causes, including endometrial hyperplasia
and carcinoma [3, 4, 5, 6, 9, 10, 11, 12].
The correlation between the clinical pattern of AUB
and the underlying endometrial histopathology is
crucial for guiding clinical decisions and improving
patient outcomes. Understanding these correlations
can help clinicians predict the likelihood of specific
pathologies based on the bleeding pattern, thereby
streamlining diagnostic pathways and ensuring timely
intervention, especially in cases of premalignant or
malignant conditions [1, 2]. Previous studies in various
populations
have
explored
this
correlation,
highlighting the spectrum of endometrial lesions
associated with AUB across different age groups [3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13]. However, the prevalence and
types of histopathological findings can vary based on
geographical location, demographic characteristics, and
specific clinical presentations.
This article aims to provide a comprehensive review of
the
clinicopathological
correlation
in
patients
presenting with abnormal uterine bleeding, drawing
evidence from a range of studies. It will synthesize
findings on the diverse histopathological patterns
observed in endometrial samples from AUB patients,
correlate these findings with various bleeding patterns,
and discuss their implications for diagnosis and
management. By consolidating current knowledge, this
review seeks to emphasize the indispensable role of
histopathology in the accurate diagnosis and effective
management of AUB, ultimately contributing to
improved women's health outcomes.
METHODS
This article is a comprehensive review of existing
literature focusing on the correlation between
abnormal uterine bleeding patterns and endometrial
histopathology. The methodology involved a systematic
approach to identify, analyze, and synthesize findings
from relevant peer-reviewed publications.
Literature Search Strategy
A thorough literature search was conducted across
multiple scientific databases to identify studies that
investigated
the
relationship
between
clinical
presentations of AUB and the corresponding
histopathological findings of endometrial samples.
Keywords and phrases used in various combinations
included: "abnormal uterine bleeding," "AUB,"
"menstrual
abnormalities,"
"endometrial
histopathology," "endometrial biopsy," "dilatation and
curettage,"
"clinicopathological
correlation,"
"endometrial hyperplasia," "endometrial carcinoma,"
"polyp,"
"adenomyosis,"
"leiomyoma,"
"FIGO
classification,"
"perimenopausal
bleeding,"
and
"postmenopausal bleeding." The search was primarily
focused on studies published in English, with no specific
date limitations to capture a broad spectrum of research
in this field.
Inclusion and Exclusion Criteria
Studies were included in this review if they:
•
Addressed abnormal uterine bleeding as a
primary clinical presentation.
•
Included histopathological examination of
endometrial tissue (e.g., from biopsy, curettage, or
hysterectomy specimens) as a diagnostic component.
•
Presented data on the correlation or spectrum
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of histopathological findings in relation to AUB
patterns.
•
Were original research articles, review articles,
or case series that provided sufficient detail for
analysis.
Studies were excluded if they:
•
Did not involve histopathological correlation.
•
Focused solely on imaging techniques without
histological confirmation.
•
Were animal studies or in vitro experiments
without direct clinical relevance to human AUB.
•
Lacked sufficient methodological detail or
presented incomplete data.
Data Extraction and Synthesis
Relevant information was systematically extracted
from the selected articles. This included:
•
Study design (e.g., retrospective, prospective).
•
Patient demographics (e.g., age groups:
reproductive, perimenopausal, postmenopausal).
•
Clinical patterns of abnormal uterine bleeding
(e.g., menorrhagia, metrorrhagia, polymenorrhea,
postmenopausal bleeding).
•
Methods of endometrial sampling (e.g.,
endometrial biopsy, dilatation and curettage,
hysterectomy).
•
The
spectrum
and
frequency
of
histopathological
findings
(e.g.,
proliferative
endometrium, secretory endometrium, disordered
proliferative endometrium, endometrial hyperplasia
(with and without atypia), endometrial polyps,
leiomyomas, adenomyosis, endometritis, endometrial
carcinoma, atrophic endometrium).
•
The correlation between specific bleeding
patterns and histopathological diagnoses.
The extracted data were then synthesized thematically
to identify common histopathological patterns
associated with AUB across different age groups and
bleeding presentations. Special attention was paid to
the prevalence of benign, premalignant, and malignant
conditions. The information was critically analyzed to
highlight consistent findings, variations, and any
emerging trends in the clinicopathological correlation
of AUB.
RESULTS
The comprehensive review of numerous studies
focusing on the correlation between abnormal uterine
bleeding
(AUB)
patterns
and
endometrial
histopathology reveals a diverse spectrum of
underlying conditions. The findings consistently
underscore the critical role of histopathological
evaluation in providing a definitive diagnosis and
guiding appropriate clinical management.
Spectrum of Histopathological Findings in AUB
Across various studies, a wide range of histopathological
findings have been reported in endometrial samples
from patients presenting with AUB. The most common
categories observed include:
•
Normal Endometrium: Despite abnormal
bleeding, a significant proportion of endometrial
biopsies, particularly in younger women, reveal normal
proliferative or secretory endometrium [5, 6, 9, 10, 11,
12]. This indicates that AUB can often be due to
functional causes, such as ovulatory dysfunction (FIGO
COEIN category), rather than structural abnormalities
[1, 2].
•
Endometrial Hyperplasia: This is a significant
finding due to its malignant potential. Hyperplasia can
be classified as without atypia (simple or complex) or
with atypia (simple or complex) [1]. Atypical hyperplasia
is considered a premalignant lesion with a substantial
risk of progression to endometrial carcinoma [1, 5, 9, 10,
11]. Studies consistently show hyperplasia as a frequent
cause of AUB, especially in perimenopausal and
postmenopausal women [3, 7, 8, 13].
•
Endometrial Polyps: These benign growths of
the endometrium are a common structural cause of AUB
(FIGO PALM category) [1, 4, 5, 6, 9, 10, 11, 12]. They can
present with various bleeding patterns, including
intermenstrual bleeding or heavy menstrual bleeding.
•
Endometrial Carcinoma: While less frequent
than benign conditions, endometrial carcinoma is the
most critical diagnosis due to its life-threatening nature
[1, 4, 5, 9, 10, 11, 12]. Its incidence increases with age,
making it a primary concern in postmenopausal
bleeding and certain cases of perimenopausal AUB [3, 7,
8, 13].
•
Disordered Proliferative Endometrium: This
term is often used for irregular, non-atypical
proliferation of the endometrium, frequently associated
with anovulatory cycles [5, 9, 10].
•
Secretory Endometrium (Irregular/Persistent):
Abnormalities in the secretory phase can also contribute
to AUB, often related to hormonal imbalances [9, 10].
•
Endometritis:
Inflammation
of
the
endometrium, often chronic, can lead to AUB and is
sometimes identified on histopathology [9].
•
Atrophic Endometrium: Commonly seen in
postmenopausal women, endometrial atrophy can also
cause AUB due to fragile blood vessels [3, 8, 13].
Correlation with Age Groups
The prevalence of specific histopathological findings
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varies significantly with age:
•
Reproductive Age Group: In this group,
functional causes like ovulatory dysfunction leading to
normal proliferative or secretory endometrium, or
disordered proliferative endometrium, are common
[2, 5, 9, 10]. Endometrial polyps and leiomyomas
(fibroids) are also frequently observed structural
causes [1, 4, 6]. Malignancy is rare but must be
considered, especially with persistent or unexplained
bleeding.
•
Perimenopausal Age Group: This period is
characterized by fluctuating hormone levels, leading to
a higher incidence of endometrial hyperplasia (both
with and without atypia) and disordered proliferative
endometrium [3, 7, 13]. Endometrial polyps and
leiomyomas remain prevalent [4, 6]. The risk of
endometrial carcinoma begins to increase in this
group, making histopathological evaluation crucial [5,
7, 8].
•
Postmenopausal Age Group: Any bleeding in
postmenopausal women is considered abnormal and
warrants immediate investigation due to the increased
risk of malignancy [3, 7, 8, 13]. Atrophic endometrium
is the most common benign finding, but endometrial
hyperplasia and carcinoma are significantly more
prevalent in this group compared to younger women
[3, 5, 8, 9, 10, 11, 12, 13]. Studies consistently highlight
the high diagnostic yield of endometrial sampling in
this demographic [3, 8].
Correlation with Bleeding Patterns
While a direct one-to-one correlation between a
specific bleeding pattern and a single histopathological
diagnosis is not always absolute, certain trends are
observed:
•
Heavy Menstrual Bleeding (Menorrhagia):
Often associated with functional causes (e.g.,
ovulatory dysfunction leading to normal or disordered
proliferative endometrium) but also commonly linked
to structural lesions like endometrial polyps and
leiomyomas [1, 4, 6]. Hyperplasia can also present with
heavy bleeding [5, 7].
•
Intermenstrual
Bleeding
(Metrorrhagia):
Endometrial polyps are a frequent cause of
intermenstrual bleeding [4, 5, 6]. Endometritis and
early endometrial hyperplasia or carcinoma can also
manifest as irregular bleeding between periods [1, 9].
•
Irregular/Infrequent Bleeding: Often points
towards anovulatory cycles, leading to disordered
proliferative or normal endometrium [2, 5]. However,
it can also be a presentation of hyperplasia or
malignancy, particularly in older women [7, 8, 13].
•
Postmenopausal Bleeding: This pattern has the
highest association with serious pathology. While
atrophic endometrium is the most common benign
finding, a significant proportion of cases reveal
endometrial hyperplasia or carcinoma, underscoring the
need for mandatory histopathological evaluation [3, 7,
8, 13].
Diagnostic Yield and "Vanishing Cancer" Phenomenon
Studies consistently report a high diagnostic yield for
endometrial sampling in cases of AUB, particularly in
older age groups [3, 9, 10, 11, 12]. However, the
phenomenon of "vanishing cancer" has been observed,
where a malignancy identified on biopsy is not found in
the subsequent hysterectomy specimen [14]. While
rare, this highlights the complexity of diagnosis and the
potential for sampling errors or complete removal of the
tumor during the initial biopsy.
DISCUSSION
The findings from this comprehensive review strongly
affirm the indispensable role of endometrial
histopathology in the diagnostic workup of abnormal
uterine bleeding (AUB). The diverse spectrum of
underlying pathologies, ranging from physiological
variations to premalignant and malignant conditions,
necessitates a definitive tissue diagnosis to guide
appropriate and timely management [1, 2, 4, 5, 6, 9, 10,
11, 12].
The prevalence of normal endometrial findings in a
substantial proportion of AUB cases, especially in
younger, reproductive-aged women, underscores the
importance of considering functional causes, such as
ovulatory dysfunction, as per the FIGO COEIN
classification [1, 2]. This highlights that not all AUB
requires aggressive intervention, and conservative
management may be appropriate after ruling out
structural or serious pathological causes. However, even
with normal histology, persistent or severe symptoms
may warrant further investigation or symptomatic
treatment.
The increasing incidence of endometrial hyperplasia and
carcinoma with advancing age, particularly in
perimenopausal and postmenopausal women, is a
consistent and critical finding across studies [3, 7, 8, 13].
This reinforces the clinical imperative to perform
endometrial sampling in these age groups, especially for
any new onset of bleeding in postmenopausal women,
which should always be considered suspicious until
proven otherwise [3, 8, 13]. The distinction between
hyperplasia with and without atypia is paramount, as
atypical hyperplasia carries a significant risk of
progression to endometrial carcinoma, necessitating
more aggressive management [1, 5, 9, 10, 11]. The
"vanishing cancer" phenomenon, though rare, serves as
a reminder of the challenges in precise diagnosis and the
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need for careful correlation with clinical context and
follow-up [14].
Endometrial polyps and leiomyomas (fibroids) are
frequently identified structural causes of AUB (FIGO
PALM categories) [1, 4, 5, 6, 9, 10, 11, 12]. While
benign, their presence can cause significant bleeding
symptoms and often require surgical intervention for
symptomatic relief. The varied presentations of these
structural lesions emphasize that a single bleeding
pattern cannot definitively predict the underlying
pathology, reinforcing the need for histopathological
confirmation.
The clinicopathological correlation, while not always
straightforward, provides valuable insights. For
instance, postmenopausal bleeding has the highest
predictive value for serious pathology, demanding
immediate and thorough investigation [3, 7, 8, 13]. In
contrast, heavy menstrual bleeding in reproductive-
aged women can be due to a wider array of benign or
functional causes, although structural lesions should
still be ruled out [1, 4, 6]. The FIGO PALM-COEIN
classification system serves as an excellent framework
for organizing clinical findings and guiding the
diagnostic workup, ensuring that both structural and
non-structural causes are systematically considered
[1].
Clinical Implications
The findings of this review have several crucial clinical
implications:
•
Personalized Management: Histopathological
diagnosis allows for personalized management
strategies, differentiating between cases requiring
medical therapy, hormonal intervention, surgical
removal of benign lesions, or definitive treatment for
malignancy.
•
Early Detection of Malignancy: Timely
endometrial sampling, especially in high-risk groups
(e.g., postmenopausal bleeding, persistent AUB in
perimenopausal women), is vital for the early
detection of endometrial hyperplasia with atypia and
carcinoma, which significantly improves prognosis [1,
3, 7, 8, 13].
•
Avoiding Unnecessary Interventions: In cases
where histopathology reveals normal or benign
functional changes, unnecessary surgical procedures
can be avoided, and patients can be managed
conservatively or with hormonal therapies.
•
Patient Counseling: A clear histopathological
diagnosis enables clinicians to provide accurate
information and counseling to patients regarding their
condition, prognosis, and treatment options,
alleviating anxiety and empowering informed decision-
making.
Limitations and Future Research
This review, while comprehensive, is subject to certain
limitations inherent in synthesizing data from multiple
studies. Variations in study designs, patient populations,
endometrial sampling techniques, and histopathological
reporting across different centers could introduce
heterogeneity. Furthermore, the review relies on
published data, and potential publication bias cannot be
entirely excluded. It also does not delve into the
molecular or genetic aspects of endometrial pathologies
associated with AUB.
Future research should focus on:
•
Prospective, large-scale multicenter studies
with standardized protocols for clinical assessment and
histopathological reporting to minimize variability.
•
Investigation into the role of newer diagnostic
modalities, such as hysteroscopy with targeted biopsy,
and their correlation with histopathology in specific AUB
patterns.
•
Research into the molecular markers that could
predict the progression of endometrial hyperplasia to
carcinoma, potentially reducing the need for invasive
procedures or guiding more precise management.
•
Studies exploring the long-term outcomes of
different histopathological diagnoses and treatment
approaches for AUB.
•
Further refinement of the FIGO PALM-COEIN
classification with molecular and genetic insights to
enhance its diagnostic precision.
In conclusion, the clinicopathological correlation of
abnormal uterine bleeding patterns with endometrial
histopathology remains a cornerstone of gynecological
practice. It is essential for accurate diagnosis,
differentiation between benign and malignant
conditions, and guiding appropriate, individualized
patient management, thereby significantly impacting
women's health.
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