Definition/General

Introduction:
-Endometrial Metaplasia refers to the replacement of normal endometrial epithelium by another type of benign epithelium
-It represents an adaptive response to various stimuli
-Common types include squamous, ciliated, and mucinous metaplasia
-It is generally benign but may be associated with underlying pathology.
Origin:
-Arises from multipotent endometrial stem cells
-Results from chronic irritation or hormonal stimulation
-May occur in response to inflammatory conditions
-Associated with estrogen stimulation in some types
-Can occur in polyps and hyperplastic endometrium.
Classification:
-Squamous metaplasia: Most common type
-Ciliated cell metaplasia: Tubal-type epithelium
-Mucinous metaplasia: Endocervical-type cells
-Eosinophilic metaplasia: Oncocytic changes
-Clear cell metaplasia: Clear cytoplasm
-Hobnail metaplasia: Protruding nuclei.
Epidemiology:
-Common finding in reproductive age women
-Squamous metaplasia most frequent
-Associated with chronic endometritis
-More common in IUD users
-Associated with endometrial polyps
-Higher frequency in perimenopausal women.

Clinical Features

Presentation:
-Often asymptomatic (incidental finding)
-Abnormal uterine bleeding (when extensive)
-Postmenopausal bleeding
-Associated with underlying pathology
-May present as infertility
-Pelvic pain (if associated with inflammation).
Symptoms:
-Irregular bleeding (if extensive)
-Menorrhagia
-Intermenstrual spotting
-Postcoital bleeding
-Pelvic discomfort
-Discharge (if associated with infection)
-Infertility (implantation issues)
-Usually minimal symptoms.
Risk Factors:
-Chronic endometritis
-IUD use
-Hormonal therapy
-Chronic inflammation
-Endometrial polyps
-Pregnancy (Arias-Stella reaction)
-Radiation therapy
-Chronic irritation.
Screening:
-Endometrial biopsy (for abnormal bleeding)
-Transvaginal ultrasound
-Hysteroscopy with biopsy
-Pap smear may show metaplastic cells
-Routine screening not required
-Investigation for underlying causes.

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Gross Description

Appearance:
-Usually not visible grossly
-May appear as focal white areas
-Smooth endometrial surface
-No specific gross features
-May be associated with polyps
-Normal endometrial thickness usually.
Characteristics:
-Microscopic finding primarily
-May show focal thickening
-White or gray patches occasionally visible
-Smooth surface
-Associated lesions may be visible
-Normal consistency.
Size Location:
-Can be focal or multifocal
-May involve entire endometrium
-Commonly in fundal region
-Can occur in polyps
-Surface and glandular involvement
-Size varies from microscopic foci to extensive involvement.
Multifocality:
-Multifocal involvement common
-Can be patchy distribution
-May affect surface and glands differently
-Associated with background pathology
-Can coexist with hyperplasia
-Multiple types may occur together.

Microscopic Description

Histological Features:
-Replacement epithelium lining surface and/or glands
-Benign cellular features
-Intact basement membrane
-No nuclear atypia
-May show associated inflammation
-Underlying stroma usually normal
-Various metaplastic types possible.
Cellular Characteristics:
-Benign epithelial cells
-Mature differentiation
-No nuclear pleomorphism
-Normal nuclear-cytoplasmic ratio
-Minimal mitotic activity
-Intact cell polarity
-Cytoplasm varies by type
-Organized architecture.
Architectural Patterns:
-Surface replacement pattern
-Glandular involvement
-Focal or diffuse distribution
-Maintains tissue architecture
-No invasion of stroma
-Sharp demarcation from normal epithelium
-May form squamous morules.
Grading Criteria:
-Benign metaplasia: No atypia
-Atypical metaplasia: Nuclear atypia present (rare)
-Extent assessment: Focal versus diffuse
-Type identification: Squamous, ciliated, mucinous, etc
-Associated pathology: Hyperplasia, polyps.

Immunohistochemistry

Positive Markers:
-Squamous metaplasia: p63
-CK5/6
-CK14
-Ciliated metaplasia: PAX8
-WT1
-Mucinous metaplasia: CEA
-MUC5AC
-All types: Cytokeratin AE1/AE3
-ER (usually positive)
-PR (variable)
-Vimentin (negative in epithelium).
Negative Markers:
-p53 wild-type pattern
-Ki-67 low proliferation
-Vimentin negative (in epithelial cells)
-TTF-1 negative (versus lung origin)
-Calretinin negative
-CDX2 negative (versus intestinal metaplasia).
Diagnostic Utility:
-p63 confirms squamous differentiation
-PAX8 supports tubal-type epithelium
-CEA highlights mucinous metaplasia
-ER/PR confirms endometrial origin
-Ki-67 low in benign metaplasia
-p53 wild-type excludes malignancy.
Molecular Subtypes:
-Hormone-responsive metaplasia
-Inflammation-associated metaplasia
-IUD-related metaplasia
-Radiation-induced metaplasia
-Pregnancy-associated metaplasia
-Idiopathic metaplasia.

Molecular/Genetic

Genetic Mutations:
-No specific mutations in benign metaplasia
-Beta-catenin pathway may be involved in squamous metaplasia
-WNT signaling alterations possible
-PTEN intact (unlike hyperplasia)
-Reactive genetic changes only
-Inflammatory pathways activated.
Molecular Markers:
-Beta-catenin expression
-Wnt pathway markers
-Inflammatory markers (if associated with endometritis)
-Hormone receptors (ER/PR)
-Differentiation markers specific to metaplastic type
-p53 wild-type.
Prognostic Significance:
-Excellent prognosis for benign metaplasia
-No malignant potential per se
-May indicate underlying pathology
-Reversible if cause removed
-Association with infertility possible
-Marker of chronic irritation.
Therapeutic Targets:
-Treat underlying cause
-Remove IUD if related
-Anti-inflammatory therapy
-Hormonal manipulation if appropriate
-Antibiotics for associated infection
-Usually no specific treatment needed.

Differential Diagnosis

Similar Entities:
-Atypical hyperplasia
-Well-differentiated adenocarcinoma
-Squamous cell carcinoma (for squamous metaplasia)
-Arias-Stella reaction
-Reactive epithelial changes
-Viral cytopathic effects
-Artifact.
Distinguishing Features:
-Benign metaplasia: No nuclear atypia
-Benign metaplasia: Organized architecture
-Atypical hyperplasia: Nuclear atypia present
-Adenocarcinoma: Invasion and atypia
-Squamous carcinoma: Invasive growth
-Arias-Stella: Secretory changes.
Diagnostic Challenges:
-Distinguishing atypical metaplasia from carcinoma
-Extensive squamous metaplasia versus squamous carcinoma
-Fragmented specimens
-Crush artifact
-Associated reactive changes
-Mixed metaplastic types.
Rare Variants:
-Papillary syncytial metaplasia
-Clear cell metaplasia
-Eosinophilic metaplasia
-Hobnail metaplasia
-Respiratory-type metaplasia
-Intestinal-type metaplasia.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Patient Information

Name: [Patient Name]\nAge: [X] years\nMRN: [Medical Record Number]\nDate of Procedure: [Date]

Clinical History

Clinical indication: [Abnormal uterine bleeding/Postmenopausal bleeding/IUD in situ/Other]\nRelevant history: [Hormone therapy/IUD use/Chronic endometritis/Other relevant findings]

Specimen Received

Specimen type: Endometrial [biopsy/curettage]\nSpecimen volume: [X] cc of tissue fragments\nFixative: 10% neutral buffered formalin

Gross Examination

The specimen consists of [X] cc of tan-pink, soft tissue fragments measuring up to [X] cm in aggregate. No gross abnormalities are identified. The tissue is entirely submitted for histological examination in [X] cassettes.

Microscopic Examination

Sections show endometrium with [focal/multifocal/diffuse] replacement of the surface and/or glandular epithelium by benign [squamous/ciliated/mucinous/eosinophilic/clear cell/hobnail] cells. The metaplastic epithelium shows mature differentiation without nuclear atypia or increased mitotic activity. The basement membrane remains intact. [Associated chronic inflammation/reactive changes] are [present/absent]. Background endometrium shows [proliferative/secretory/atrophic/inflammatory] pattern.

Immunohistochemistry (if performed)

[Squamous metaplasia: p63 positive, CK5/6 positive]\n[Ciliated metaplasia: PAX8 positive]\n[Mucinous metaplasia: CEA positive, MUC5AC positive]\n[Other relevant markers as indicated]

Final Diagnosis

ENDOMETRIAL [SQUAMOUS/CILIATED/MUCINOUS/OTHER] METAPLASIA\n\nType: [Specify metaplastic type]\nExtent: [Focal/Multifocal/Diffuse]\nAtypia: [Absent/Present]

Comments

• Benign metaplastic change with no evidence of atypia or malignancy.\n• Metaplasia represents an adaptive response to chronic irritation or hormonal stimulation.\n• Clinical correlation recommended to identify and address underlying cause.\n• [Consider IUD removal if IUD-related metaplasia]\n• [Consider treatment of chronic endometritis if inflammatory changes present]\n• No specific treatment usually required for the metaplasia itself.

Reported By

Dr. [Pathologist Name], MD\nConsultant Pathologist\nDate: [Report Date]