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PATHOLOGY of the UTERUS - Coggle Diagram

- - - - covered by squamous epithelium
        
        metaplastic changes can lead to occlusion of the glands
        
        Naboth cysts
    - - covered by glandular epithelium
  - - - chlamydia
        
        trichomonas
        
        ureaplasma
        
        candida
        
        neisseria
        
        HSV
        
        papilloma
        
        common feature in PAP test smear
    - - endocervical polyps
        
        frequent (3% of adult women)
        
        inflammatory
        
        benign-looking glands interspersed in a fibromyxoid stroma
        
        no atypia
      - micro-glandular hyperplasia
        
        associated with oral contraceptives
        
        frequent squamous metaplasia
        
        architectural disarray
        
        no cytological atypia
        
        epithelial component predominates
        (exclusively made of glands)
    - - risk factors
        
        early sexual activity
        
        number of partners
        
        history of pregnancies
        
        genetic predisposition
        
        HPV
        
        HPV
        
        95% carcinomas; 98% condylomas
        
        risk
        
        low: 6, 11, 42, 43, 44
        
        intermediate: 35, 39, 51, 56, 59
        
        high: 16, 18, 31, 33, 45, 52, 58
        
        low risk: condyloma
        
        high risk: high grade dyaplasia
        
        2 more items...
        
        detection
        
        morphology: koilocytes (aspecific)
        
        IHC: HPV protein (e.g.p16), no phenotype definition
        
        molecular detection and typing
        
        lesion: KOILOCYTOSIS
        
        altered nuclear-to-cytoplasmic ratio
        
        bi-nucleation
        
        perinuclear halo
      - screening
        
        PAP test
        
        HPV test
        
        aka Molecular screening test
        
        more commonly used today
        
        program in Piedmont
        
        target population: 25-65 years
        
        invitation letter every 3 (PAP) - 5 (DNA) years
        
        level I
        
        cytology (PAP-TEST)
        
        triage molecular test for HPV-DNA
        
        level II
        
        colposcopy + biopsy
        
        laser or conization
      - pre-invasive epithelial lesions
        
        CIN
        
        dysplastic process still confined within the basal membtane (intraepithelial), which is a precursor of carcinoma
        
        grades
        
        CIN1
        
        low-grade
        
        self-limiting
        
        CIN3
        
        high-grade
        
        potential to transform in invasive cancer
        
        CIN2
        
        intermediate category
        
        unclear biological potential
        
        distinguishable at H&E with poor reproducibility
        
        age: 25-30 years
        
        about 20 years younger than women developing invasive SCC
        
        HPV-related
        
        abnormal epithelial maturation (loss of polarity, cellular disarray)
        
        mitoses (even atypical)
        
        nuclear atypia
        
        koilocytosis
        
        SIL
        
        aka Bethesda system
        
        levels
        
        CIN2-3 corresponds to H-SIL
        
        abnormal cell proliferation
        (more ptonounced)
        
        nuclear atypia
        (more pronounced)
        
        poor maturation in all three epithelial layers
        
        mitotic figures in all three epithelial layers
        
        CIN1 corresponds to L-SIL
        
        abnormal cell proliferation
        
        nuclear atypia (increased nucleus/cytoplasm ratio, irregular chromatin and nuclear contours)
        
        poor maturation in the basal layer (preserved upper and intermediate layers)
        
        mitotic figures in basal layer only
        
        KOILOCYTOSIS
        
        superficial cells are orange because the Papanicolau stain colours keratinized cells
        
        before the evaluation check sample adequacy
        
        endocervix and exocervix samples are needed
        
        if columnar cells are not present, the sample is not not adequate
        
        the lesion may arise in the endocervix
        
        additional tests
        
        Ki-67 proliferation index
        
        to evaluate where proliferating cells are
        
        in low-grade dysplasia: proliferating cells do not exceed the lower half of the epithelium
        
        basally-located
        
        in high-grade dysplasia: proliferating cells invade the entire epithelium
        
        p16
        
        proof of HPV presence (high-risk)
        
        helpful in grading the dysplasia
        
        p16 only positive in the lower part of the epithelium: low-grade dysplasia
        
        p16 positive in the full thickness of the epithelium: high-grade dysplasia
      - carcinomas
        
        squamous cell carcinoma
        
        microinvasion
        
        variants
        
        verrucous
        
        clear cell
        
        basaloid
        
        foci <1 mm surrounded by lymphocytic infiltrate
        
        high degree of dysplasia
        
        the degeneration from first degree dysplasia to invasive phase takes decades
        
        adenocarcinomas / adenosquamous (10%)
        
        found in any place in which you can have SCC
        
        more frequent in the cervix
        
        glandular & squamous cells coexist
        
        staging
        
        on conization or surgical sample
        
        stage 0
        
        "in situ"
        
        stage 1
        
        limited to the cervix
        
        survival 90%
        
        further division
        
        Ia
        
        depth of invasion <5 mm
        
        horizontal extension <7 mm
        
        Ib
        
        dimensions >Ia
        
        stage II
        
        extension to the vagina
        
        not to the pelvic walls
        
        survival 75%
        
        stage III
        
        extension to the pelvis or upper third of the vagina
        
        survival 35%
        
        stage IV
        
        estension to the adjacent organs (rectum, bladder)
        
        survival 10%
        
        small cell carcinoma
        
        5% of cervical cancers
        
        poorly differentiated
        
        very aggressive
        
        HPV-related or not
        
        usually found during the interval between two screening tests
- - - - endometriosis
        
        possibilities
        
        adenomyosis
        
        presence of endometrial tissue in the wall of the uterus, intramural or intraparietal
        
        full blown endometriosis
        
        presence of endometrial tissue in locations other than the uterus, e.g. ovaries
        
        pathogenesis
        
        hypothesis:
        RETROGRADE MENSTRUATION
        
        coherent with the fact that the most common locations are outside of the uterus
        
        possible complications
        
        pain
        
        desmoplastic reaction with sub-occlusion of the bowel
        
        bleeding because of menstruation in ectopic locations
        
        hemoperitoneum and chocolate cysts formation may happen
        
        differential diagnosis
        
        metastases from an adenocarcinoma of the rectum
        
        in endometriosis, the epithelium is glandular
        
        in rectal AC, it involves the surface
        
        endometrial tissue is normal (no atypia),
        JUST DISPLACED
        
        epithelial & stromal components together
        
        glands alone may be a signal of neoplasia
        
        endometrial stroma marker:
        CD10
        
        some rare cases of endometrial tissue displaced to the lungs has been found (unknown pathogenesis)
      - dysfunctional uterine bleeding
        
        definition: bleeding >5 days cause in women of childbearing age
        
        histology
        
        useful to understand whether it is more in the proliferative phase, in the secretory phase or in the premenstrual phase
        
        the timing of the menstrual cycle has to match what the pathologist says
        
        otherwise: dysfunctional
        
        causes
        
        adenomyosis, anovulatory cycle, chronic inflammation, drugs with hormonal side effects, ectopic pregnancy, endocrine disorder, endometrial carcinoma (5-15% of post-menopausal bleeding), endometrial hyperplasia, endometrial polyp, endometriosis, exogenous hormones, idiopathic stromal predecidualization in post-menopausal women, leiomyoma, luteal phase defect, malnutrition, obseity, ovarian granulosa-theca tumor, precocious puberty, pregnancy complication
        
        subgroups
        
        inadequate proliferative phase --> proliferative epithelium
        
        inadequate secretory phase --> secretory endothelium
        
        irregular shedding --> menstruation type of endometrium before the bleeding should start
        
        membranous dysmenorrhea
      - inflammatory diseases
        
        endometritis
        
        in women with PID, post-partum, post-abortion, tuberculosis (miliary or TB salpingitis), symptomatic bacterial vaginosis
        
        chronic, with agglutination of lymphocytes and plasma cells
        
        plasma cells marker: CD-138
        
        15% unknown cause
        
        often asymptomatic
        
        weakly proliferative glands
        
        plasma cells, histiocytes, lymphocytes and lymphoid follicles
        
        myometrium is usually spared unless inflammation is severe
        
        PID
        
        involvement of:
        
        endometritis
        
        salpingitis +/- ovarian involvement
        
        tubaric abscess
        
        pelvic peritonitis
        
        complications depend on the extent of the disease in the pelvic area
        
        transmission:
        
        sexually-transmitted pathogens
        
        lymphatic or hematogenous spread
    - - hyperplasia without atypia
        
        epithelial-stromal proliferation with architectural disarray WITHOUT CYTOLOGICAL ATYPIA
        
        risk factors
        
        obesity
        
        POS
        
        diabetes
        
        risk of evolution into endometrial cancer
        
        1-3%
      - endometrial intraepithelial neoplasia
        
        aka hyperplasia WITH ATYPIA
        
        dysplastic changes without invasion
        
        premalignant lesion
        
        1/3 of cases with EIN at biopsy have endometrial cancer at histerectomy
        
        45x risk of developing endometrial cancer as compared to the general population
        
        molecular features
        
        PTEN inactivation
        
        KRAS mutation
        
        MMR deficiency
      - endometrial carcinoma
        
        +++ invasion
        
        risk factors
        
        diabetes
        
        obesity
        
        hypertension
        
        infertility
        
        MMR system abnormalities (Lynch syndrome)
        
        age >40 years
        (peak at 60)
        
        pathology
        
        macroscopic
        
        friable
        
        infiltrative mass
        
        polypoid / exophytic
        
        don't measure the size of the lesion, but rather the depth of the invasion
        
        histology
        
        endometroid (adeno-)carcinoma
        
        micro: "endometrioid" glands, back-to-back, scarce stroma with no desmoplasia
        
        poor mucin content in cells
        
        columnar cells
        
        no specific marker
        
        G1, G2 and G3
        
        depending on the % of gland formation
        
        non-endometrioid carcinoma
        
        mucinous
        
        serous (BRCA1+)
        
        clear cell
        
        mixed malignant Mullerian tumors (CARCINOSARCOMA)
        
        molcular classification
        
        mismatch repair deficiency
        
        p53 mutant
        
        POLE-mutant
        
        most frequent type of alteration in endometrial cancer
        
        unclassified
        
        important to determine prognosis
        
        POLE-mutant subgroup has an excellent prognosis
        
        lots of errors
        
        neoantigens load
        
        immune response activation
        
        p53 mutant subgroup is associated with a very bad prognosis
        
        staging
        
        T stage
        
        T1a: invasion of less than one half of the myometrium
        
        T1b: invasion of more than one half of the myometrium (including endocervix)
        
        T2: cervical stroma invasion
        
        T3: invasion of serosa, ovaries, ligaments and vagina
        
        T4: invasion of adjacent organs (e.g. rectum, bladder)
      - stromal neoplasm
        
        LEIOMYOMA
        
        frequent
        
        aka fibroma
        
        variable size
        
        the bigger ones are in the subserosal component of the wall, growing in pelvis without any kind of sign and symptom
        
        spindle cell proliferation of stromal cells with smooth muscle differentiation and bland cytological atypia
        
        hypercellularity is an important parameter
        
        no necrosis and low mitotic index
        
        special entity: deficit of fumarate hydratase
        
        LEIOMYOSARCOMA
        
        rare
        
        similar to leiomyoma, but >10 mitoses x HPF
        
        it is important to count the mitotic figures in order to understand the severity of the lesion
        
        cellular atypia, increased cellularity and necrosis
        
        variants
        
        epithelioid
        
        spindle cell
        
        pleomorphic
        
        mixoid
        
        smooth muscle IHC markers
        
        desmin
        
        sm-actin
        
        caldesmon
        
        "STUMP"
        
        borderline lesions
        
        active mitotic activity, but no full criteria for leiomyosarcoma
        
        ENDOMETRIAL STROMAL SARCOMA
        
        from specialized loose connective tissue between endometrial glands
        
        rare
        
        forms
        
        low-grade
        
        IHC markers of endometrioid stroma (CD10) and variable expression of smooth muscle markers
        
        fusion: KAZF1-SUZ12
        
        high-grade
        
        small, undifferentiated cells, cyclin D1 overexpression, CD10 frequently negative
        
        fusion: YWHAE-FAM22