Definition/General

Introduction:
-Endometrial Adenomyosis is the presence of ectopic endometrial glands and stroma within the myometrium
-It represents benign invasion of endometrium into uterine muscle
-The ectopic endometrium is surrounded by hypertrophic and hyperplastic smooth muscle
-It is a common cause of heavy menstrual bleeding and dysmenorrhea.
Origin:
-Results from direct extension of basalis endometrium into myometrium
-May involve invagination of surface endometrium
-Associated with disrupted junctional zone
-Hormonal factors play a role in pathogenesis
-Trauma and inflammation may predispose.
Classification:
-Diffuse adenomyosis: Widespread myometrial involvement
-Focal adenomyosis: Localized involvement (adenomyoma)
-Superficial adenomyosis: Junctional zone involvement
-Deep adenomyosis: Extends deep into myometrium
-Classification by depth: >2.5mm from basalis layer.
Epidemiology:
-Common in multiparous women aged 35-50 years
-Prevalence 20-30% in hysterectomy specimens
-Associated with previous uterine surgery
-Higher incidence in perimenopausal women
-Often coexists with endometriosis and leiomyomas.

Clinical Features

Presentation:
-Heavy menstrual bleeding (menorrhagia)
-Severe dysmenorrhea
-Enlarged uterus
-Chronic pelvic pain
-Infertility (implantation problems)
-Dyspareunia
-Pressure symptoms
-May be asymptomatic (20-30%).
Symptoms:
-Menorrhagia (80-90% of symptomatic cases)
-Dysmenorrhea (progressive)
-Metrorrhagia
-Chronic pelvic pain
-Uterine tenderness
-Bloating and pressure
-Urinary frequency
-Fatigue (due to anemia).
Risk Factors:
-Multiparity
-Age 35-50 years
-Previous uterine surgery (C-section, D&C)
-Endometriosis
-Short menstrual cycles
-Early menarche
-Nulliparity (in some studies)
-High BMI
-Smoking.
Screening:
-Transvaginal ultrasound (first-line)
-MRI (most accurate)
-3D ultrasound
-Hysteroscopy (limited value)
-Endometrial biopsy (usually normal)
-CA-125 may be elevated
-Clinical history and examination.

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Gross Description

Appearance:
-Enlarged, globular uterus
-Thickened myometrium
-Ill-defined areas of soft, brown tissue
-Cystic spaces containing blood or fluid
-Honeycombed appearance
-Asymmetric uterine enlargement
-Cut surface shows trabeculated pattern.
Characteristics:
-Soft, spongy areas in myometrium
-Hemorrhagic foci
-Cystic spaces of varying sizes
-Brown discoloration
-Irregular borders
-Myometrial thickening
-Loss of normal architecture.
Size Location:
-Can involve any part of myometrium
-Common in posterior wall
-May involve junctional zone primarily
-Focal lesions (adenomyomas) 2-5cm
-Diffuse involvement causes global enlargement
-Extension to serosal surface possible.
Multifocality:
-Multifocal involvement common
-Bilateral involvement frequent
-May have skip lesions
-Associated with endometriosis (30-40%)
-Coexistent leiomyomas (50-60%)
-Variable depth of penetration.

Microscopic Description

Histological Features:
-Endometrial glands within myometrium
-Endometrial stroma surrounding glands
-Smooth muscle hyperplasia and hypertrophy
-Hemorrhage and hemosiderin deposition
-Fibrosis around ectopic foci
-Chronic inflammation.
Cellular Characteristics:
-Benign endometrial glands
-Typical endometrial stromal cells
-Smooth muscle cell hyperplasia
-Hemosiderin-laden macrophages
-Chronic inflammatory cells
-Fibroblasts and myofibroblasts
-No nuclear atypia.
Architectural Patterns:
-Irregularly distributed endometrial glands
-Variable gland sizes
-Cystic dilatation possible
-Surrounding smooth muscle reaction
-Poorly defined borders
-Depth >2.5mm from basalis layer diagnostic.
Grading Criteria:
-Superficial adenomyosis: Confined to inner myometrium
-Deep adenomyosis: Extends to outer myometrium
-Focal adenomyosis: Well-defined lesion (adenomyoma)
-Diffuse adenomyosis: Widespread involvement
-Assessment of depth and extent.

Immunohistochemistry

Positive Markers:
-CD10 positive (endometrial stroma)
-ER positive (glands and stroma)
-PR positive (variable)
-Smooth muscle actin (surrounding muscle)
-Desmin positive (smooth muscle)
-Caldesmon positive
-Cytokeratin positive (glands).
Negative Markers:
-p53 wild-type
-Ki-67 low
-CD68 (in macrophages only)
-S-100 negative
-Melanoma markers negative
-Lymphoid markers negative.
Diagnostic Utility:
-CD10 confirms endometrial stromal origin
-Smooth muscle actin highlights muscle component
-ER/PR shows hormonal responsiveness
-Cytokeratin outlines glandular component
-p53 excludes malignancy
-Ki-67 low proliferation.
Molecular Subtypes:
-Hormone-responsive adenomyosis
-Estrogen-dependent type
-Progesterone-resistant type
-Inflammatory subtype
-Fibrotic subtype
-Associated with endometriosis.

Molecular/Genetic

Genetic Mutations:
-KRAS mutations (in some cases)
-PIK3CA mutations
-PTEN alterations
-Beta-catenin pathway involvement
-DICER1 mutations
-Chromosomal aberrations uncommon
-Clonal analysis shows polyclonality.
Molecular Markers:
-Estrogen receptor expression
-Progesterone receptor expression
-Aromatase expression
-Cox-2 overexpression
-VEGF expression
-Matrix metalloproteinases
-Inflammatory mediators.
Prognostic Significance:
-Benign condition with good prognosis
-Symptoms improve after menopause
-Risk of infertility
-Recurrence after conservative surgery
-No malignant potential
-Quality of life significantly affected.
Therapeutic Targets:
-Hormonal therapy: GnRH agonists
-Progestins
-LNG-IUD
-Aromatase inhibitors
-Anti-inflammatory agents
-Uterine artery embolization
-Focused ultrasound
-Hysterectomy (definitive).

Differential Diagnosis

Similar Entities:
-Leiomyoma
-Endometrial polyp
-Endometriosis
-Adenosarcoma
-Endometrial stromal sarcoma
-Leiomyosarcoma
-Metastatic carcinoma.
Distinguishing Features:
-Adenomyosis: Endometrial glands in myometrium
-Leiomyoma: Pure smooth muscle
-Endometriosis: Outside uterus
-Adenosarcoma: Stromal atypia
-ESS: Stromal overgrowth
-Leiomyosarcoma: Smooth muscle atypia.
Diagnostic Challenges:
-Distinguishing from leiomyoma with entrapped glands
-Adenosarcoma in elderly patients
-Sampling limitations
-Crush artifact
-Associated pathology
-Depth measurement accuracy.
Rare Variants:
-Adenomyoma (focal adenomyosis)
-Cystic adenomyosis
-Adenomyosis with smooth muscle metaplasia
-Atypical adenomyosis
-Adenomyosis with endometrioid carcinoma.

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: [Heavy menstrual bleeding/Dysmenorrhea/Pelvic pain/Enlarged uterus]\nSymptoms: [Menorrhagia/Severe dysmenorrhea/Chronic pelvic pain/Pressure symptoms]\nProcedure: [Total hysterectomy +/- bilateral salpingo-oophorectomy]

Specimen Received

Specimen type: [Total hysterectomy/Hysterectomy with bilateral adnexa]\nOrgan weights: Uterus [X] grams, [Ovaries/Fallopian tubes] [X] grams\nFixative: 10% neutral buffered formalin

Gross Examination

The uterus measures [X] x [X] x [X] cm and weighs [X] grams. The serosal surface is [smooth/irregular]. The cervix measures [X] cm in length. On sectioning, the myometrium is [thickened/normal] measuring up to [X] cm in thickness and shows [ill-defined areas of soft, brown tissue/honeycombed appearance/trabeculated pattern]. Cystic spaces containing [blood/fluid] are [present/absent]. The endometrium measures [X] mm in thickness and appears [normal/irregular]. [Leiomyomas/Other lesions] are [present/absent].

Microscopic Examination

Sections show endometrial glands and stroma present within the myometrium at a depth of [X] mm from the basalis layer. The ectopic endometrial glands are lined by benign epithelium without atypia and are surrounded by endometrial stroma. The myometrium shows [smooth muscle hyperplasia and hypertrophy/reactive changes] around the ectopic endometrial foci. Hemosiderin-laden macrophages and chronic inflammatory cells are present. The adenomyosis is [focal/diffuse] in distribution and extends [superficially/deeply] into the myometrium. The surface endometrium shows [proliferative/secretory/atrophic] pattern. [Associated findings: leiomyomas/endometriosis] are [present/absent].

Final Diagnosis

ADENOMYOSIS\n\nType: [Diffuse/Focal] adenomyosis\nDepth of invasion: [X] mm from basalis layer\nExtent: [Superficial (<1/3 myometrium)/Deep (>1/3 myometrium)]\nAssociated findings: [Leiomyomas/Endometriosis/None]

Comments

• Adenomyosis is a benign condition characterized by ectopic endometrial glands and stroma within the myometrium.\n• Diagnosis requires invasion >2.5mm from the basalis layer.\n• Associated with dysmenorrhea, menorrhagia, and uterine enlargement.\n• Symptoms typically improve after menopause due to hormonal dependency.\n• No malignant potential.\n• Clinical correlation with preoperative symptoms recommended.

Reported By

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