Explore key female reproductive pathologies: HPV-related cancers, endometrial hyperplasia, ovarian tumors, PCOS, & pregnancy complications. Essential notes for
SummaryThis document outlines key pathologies of the female reproductive system, covering disorders of the vulva, cervix, uterus, fallopian tubes, ovaries, and conditions related to pregnancy. It delves into the etiology, morphology, clinical presentation, and prognosis of various benign and malignant conditions, including inflammatory processes, neoplastic changes, and functional disorders. Emphasis is placed on the role of HPV in cervical and vulvar cancers, the mechanisms behind endometrial hyperplasia and carcinoma, the diverse origins of ovarian tumors, and the pathophysiology of pregnancy-related complications like ectopic pregnancy and preeclampsia. Key Points- Vulvar Disorders: Vulvitis can be caused by contact dermatitis or infections. Non-neoplastic epithelial disorders like Lichen Sclerosus and Lichen Simplex Chronicus require biopsy for differentiation and risk assessment. HPV subtypes 6 and 11 cause condylomata acuminata, while high-risk HPV types (16, 18) are associated with vulvar carcinoma through VIN. Extramammary Paget disease presents as a plaque but is typically not associated with underlying malignancy. - Cervical Disorders: Cervicitis is common, often caused by STIs. Cervical neoplasia is predominantly HPV-driven, occurring in the transformation zone. CIN grades (LSIL, HSIL) are managed based on severity, with the Pap smear being a highly effective screening tool. Invasive cervical carcinoma, predominantly squamous cell, arises from persistent HPV infection and can lead to significant morbidity and mortality. - Uterine Disorders: Endometritis can be acute or chronic, often linked to infection or retained products. Adenomyosis involves endometrial basal layer growth into the myometrium, causing pain and heavy bleeding. Endometriosis, ectopic endometrial tissue, causes pain and infertility. Abnormal uterine bleeding has multiple causes, frequently related to anovulation. Endometrial hyperplasia is a precursor to endometrial carcinoma, with atypia increasing risk. Endometrial carcinoma has two main types (Endometrioid and Serous), differing in pathogenesis and behavior. Leiomyomas are common benign smooth muscle tumors, while leiomyosarcomas are rare, aggressive malignancies arising de novo. - Fallopian Tube and Ovarian Disorders: Salpingitis is typically part of PID with potential for infertility and ectopic pregnancy. Ovarian tumors are diverse, originating from surface epithelium (most common, including serous, mucinous, endometrioid), germ cells (teratomas), or sex cord-stroma. Polycystic Ovarian Disease (PCOS) is characterized by hormonal imbalances and multiple ovarian cysts. - Diseases of Pregnancy: Placental infections can be ascending or haematogenous. Ectopic pregnancies are primarily tubal and can be life-threatening due to rupture. Gestational Trophoblastic Disease (GTD) includes hydatidiform moles, invasive moles, and choriocarcinoma, all characterized by hCG production and varying degrees of malignancy. Preeclampsia/Eclampsia is a pregnancy-specific hypertensive disorder linked to placental vascular dysfunction and antiangiogenic factors, resolving post-delivery. - Detailed Notes Female Reproductive Pathology — Must-Know Notes--- 1. Disorders of the Vulva Conditions covered: Vulvitis · Non-neoplastic Epithelial Disorders · Tumours --- Vulvitis Key causes: Contact dermatitis · Infections · Bartholin gland obstruction - Contact Irritant Dermatitis — reaction to urine, soaps, detergents, antiseptics, deodorants; presents as erythematous, weeping, crusting papules and plaques - Allergic Dermatitis — similar appearance; triggered by perfumes, additives in creams/lotions - Chronic scratching (pruritus) worsens both — important point - Infectious causes (mostly STIs): - - HPV → condyloma acuminatum and VIN - HSV-1/2 → genital herpes (vesicular eruption) - N. gonorrhoeae → suppurative infection of vulvovaginal glands - Treponema pallidum → primary chancre at vulvar inoculation site - Candida spp. → vulvitis - Bartholin Gland Complication — obstruction of excretory ducts → painful Bartholin cyst → abscess formation - --- Non-Neoplastic Epithelial Disorders Conditions covered: Lichen Sclerosus · Lichen Simplex Chronicus Lichen Sclerosus - Histology: Thinning of epidermis, loss of rete pegs, hydropic degeneration of basal cells, dermal fibrosis, scant perivascular mononuclear infiltrate - Appearance: Smooth white plaques/papules (leukoplakia); entire vulva may become atrophic and stiffened; vaginal orifice constricted - Who gets it: All age groups but most common in postmenopausal women - Pathogenesis: Likely autoimmune — activated T cells in subepithelial infiltrate; associated with other autoimmune disorders - Key clinical point: Benign BUT 1–5% develop squamous cell carcinoma of the vulva - Lichen Simplex Chronicus - Histology: Epithelial thickening (especially stratum granulosum), hyperkeratosis, increased mitotic activity in basal/suprabasal layers — NO epithelial atypia - Cause: Consequence of chronic irritation/pruritus from underlying inflammatory dermatosis - Key clinical point: Isolated lesions have no increased cancer risk BUT often found at margins of established vulvar cancer — possible association with neoplasia - Important: Lichen sclerosus and lichen simplex chronicus can coexist in the same person; both can appear as leukoplakia — biopsy is essential to differentiate from malignant lesions - --- Tumours Conditions covered: Condylomas · Carcinoma of the Vulva · Extramammary Paget Disease Condylomas - Condyloma Lata — flat, moist, minimally elevated lesions; occur in secondary syphilis; not common today - Condylomata Acuminata — papillary or flat rugose warty lesions; occur anywhere on anogenital surface; single or multiple - - Caused by HPV subtypes 6 and 11 (low-risk → low malignant transformation risk) - Histology: Koilocytosis — perinuclear cytoplasmic vacuolization + wrinkled nuclear contours — hallmark of HPV infection - Sexually transmitted; identical lesions occur in males (penis, perianal area) Carcinoma of the Vulva - Represents ~3% of all female genital tract cancers; mostly women 60 years - ~90% are squamous cell carcinomas; remainder are adenocarcinomas or basal cell carcinomas - Two distinct pathways: - Feature HPV-Related Non-HPV-Related --- --- --- Age Middle-aged women Older women Precursor VIN (vulvar intraepithelial neoplasia) Lichen sclerosus HPV type High-risk HPV 16 & 18 Not HPV-associated Tumour type Warty/basaloid, multifocal, poorly differentiated Unifocal, well-differentiated, keratinizing SCC Risk factors Cigarette smoking, immunodeficiency Reactive epithelial changes - VIN — precancerous epithelial change; may progress to carcinoma in situ; progression to invasive carcinoma not inevitable but possible after many years - Morphology: Early = leukoplakia (white patches); ¼ are pigmented; later become exophytic or ulcerative tumours - Spread: Remain confined for years, then spread to regional lymph nodes first - Prognosis: Tumours 20% of cervical cancers; normally activates AMPK → regulates cell growth via mTOR; also mutated in Peutz-Jeghers syndrome and lung cancer - HPV alone is NOT sufficient — immune status, hormonal factors, co-infections, and mutations (e.g. LKB1) all contribute - Risk Factors for CIN and Invasive Carcinoma - Early age at first intercourse - Multiple sexual partners - Male partner with multiple previous partners - Persistent high-risk HPV infection - Cigarette smoking - HIV/immunodeficiency - CIN Grading Grade Old Name New Name Features --- --- --- --- CIN I Mild dysplasia LSIL Dysplasia lower ⅓ of epithelium; koilocytosis in superficial layers CIN II Moderate dysplasia HSIL Dysplasia extends to middle ⅓; delayed keratinocyte maturation; mitoses in middle third CIN III Severe dysplasia/CIS HSIL Almost complete loss of maturation; all layers affected; no koilocytosis; marked atypia - CIN peaks at age 30; invasive carcinoma peaks at age 45 — reflects years of progress