Practice 6 structured short- and long-answer medical questions on Female Reproductive Pathology — Must-Know Notes. Review model answers for exam revision.
Answer: This 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 <2 cm → ~90% 5-year survival; advanced stage → only 20% survive 10 years #### Extramammary Paget Disease - Intraepidermal proliferation of malignant epithelial cells occurring in the skin of the vulva - **Key difference from breast Paget disease:** In the breast, almost always associated with underlying carcinoma; in the vulva, majority have NO demonstrable underlying tumour - Paget cells arise from epidermal progenitor cells; occasionally associated with subepithelial tumour from sweat glands - **Appearance:** Red, scaly, crusted plaque — may mimic inflammatory dermatitis - **Histology:** Large epithelioid cells with abundant pale granular cytoplasm and cytoplasmic vacuoles infiltrating the epidermis; mucin present (PAS positive) — distinguishes it from vulvar melanoma (which lacks mucin) - **Behaviour:** May persist for years without invasion; if associated sweat gland tumour present → local invasion and metastasis possible → poor prognosis once metastasis occurs --- ## 2. Disorders of the Cervix **Conditions covered:** Cervicitis · Neoplasia of the Cervix · Invasive Carcinoma · Endocervical Polyp --- ### Cervicitis **Key causes:** Infectious (STIs) · Non-infectious - Extremely common; presents with purulent vaginal discharge - Normal vaginal flora (streptococci, staphylococci, enterococci, E. coli) makes interpretation of cultures difficult — only known pathogens are significant - **Important pathogens:** - **C. trachomatis** — most common, accounts for up to 40% of STD clinic cases; causes prominent lymphoid follicles on histology - Ureaplasma urealyticum, T. vaginalis, Candida, N. gonorrhoeae, HSV-2, HPV - **HSV** — important because maternal-infant transmission during childbirth can cause serious/fatal neonatal herpes - **Morphology:** - Acute cervicitis — uncommon; limited to postpartum period; caused by staphylococci/streptococci - Chronic cervicitis — common in all reproductive-age women; epithelial hyperplasia, reactive changes, squamous metaplasia of columnar epithelium --- ### Neoplasia of the Cervix **Key concepts:** Transformation zone · HPV pathogenesis · CIN grading · Pap smear · Vaccine #### Pathogenesis - Most cervical tumours are epithelial and caused by oncogenic HPV strains - **Transformation zone** — where columnar endocervical epithelium meets squamous exocervical epithelium; with puberty, columnar epithelium everts onto exocervix and undergoes squamous metaplasia → forms transformation zone - HPV has tropism for immature squamous cells of the transformation zone - Most HPV infections are transient and cleared within months by immune response - Persistent infection → CIN → invasive carcinoma #### HPV Molecular Mechanism - HPV encodes two key oncoproteins: **E6** and **E7** - **E6** → binds and inactivates **p53** tumour suppressor - **E7** → binds and inactivates **Rb** tumour suppressor - Together they promote cell growth and accumulation of further mutations → carcinogenesis - **High-risk HPV** (types 16, 18) → account for ~70% of CIN and cervical carcinoma; integrate into host genome → drives progression - **Low-risk HPV** (types 6, 11) → condylomas; remain as episomal DNA; do not integrate - **LKB1 tumour suppressor** — somatically mutated in >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 progression - Higher grade = greater likelihood of progression (but even high-grade lesions can regress) - **Management:** LSIL → conservative observation; HSIL → surgical excision (cone biopsy); lifelong follow-up for HSIL patients #### Pap Smear - Cells scraped from transformation zone and examined microscopically - Most successful cancer screening test ever developed - Has dramatically lowered invasive cervical cancer incidence - Paradox: incidence of CIN has increased (better detection) while invasive cancer has decreased #### HPV Vaccine - Quadrivalent vaccine covers types 6, 11, 16, 18 - Very effective in preventing HPV infection → expected to lower genital warts and cervical cancer - Does NOT replace routine screening — many women already infected; vaccine covers only some oncogenic serotypes --- ### Invasive Carcinoma of the Cervix - **Types:** SCC 75% · Adenocarcinoma + mixed adenosquamous 20% · Small cell neuroendocrine <5% - All types caused by HPV - Adenocarcinoma proportion increasing — due to decreasing SCC incidence and poor detection of glandular lesions by Pap smear - Peak incidence ~45 years (10–15 years after CIN) - **Morphology:** Develops in transformation zone; ranges from microscopic stromal invasion to grossly exophytic tumours; "barrel cervix" when tumour encircles cervix; parametrial extension affixes uterus to pelvic structures - **Spread:** Risk of lymph node spread correlates with depth of invasion; <1% risk at <3mm depth → >10% risk once invasion exceeds 3mm - **Clinical features:** Unexpected vaginal bleeding, leukorrhea, dyspareunia, dysuria; seen in women never screened or not screened for many years - **Treatment:** Hysterectomy + lymph node dissection; cone biopsy for small microinvasive lesions - **Death:** Most commonly from local invasion — renal failure due to ureteral/bladder obstruction is common cause of death --- ### Endocervical Polyp - Benign polypoid masses protruding from endocervical mucosa (sometimes through exocervix) - Soft, glistening surface with cystically dilated spaces filled with mucinous secretions - Lined by mucus-secreting columnar cells; stroma is oedematous with scattered mononuclear cells - Chronic inflammation → squamous metaplasia and ulceration - **May bleed** — causes concern but has NO malignant potential --- ## 3. Disorders of the Uterus **Conditions covered:** Endometritis · Adenomyosis · Endometriosis · Abnormal Uterine Bleeding · Proliferative Lesions (Endometrial Hyperplasia · Endometrial Carcinoma · Endometrial Polyps · Leiomyoma · Leiomyosarcoma) --- ### Endometritis **Key types:** Acute · Chronic - Classified as acute (neutrophilic response) or chronic (lymphoplasmacytic response) - **Diagnosis of chronic endometritis requires plasma cells** — lymphocytes are normally present so they are not diagnostic - Common causes: - PID — N. gonorrhoeae or C. trachomatis - Retained products of conception (post-miscarriage/delivery) - Foreign body (e.g. intrauterine device) - Tuberculosis → granulomatous endometritis (associated with TB salpingitis and peritonitis; common in endemic areas) - **Histology:** Neutrophilic infiltrate in superficial endometrium and glands + stromal lymphoplasmacytic infiltrate; prominent lymphoid follicles more common in chlamydial infection - **Clinical features:** Fever, abdominal pain, menstrual abnormalities; increased risk of infertility and ectopic pregnancy from fallopian tube scarring --- ### Adenomyosis - Growth of the **basal layer** of endometrium down into the myometrium - Nests of endometrial stroma, glands, or both found deep in myometrium between muscle bundles - Reactive myometrial hypertrophy → enlarged, globular uterus with thickened wall - Glands derive from stratum basalis → **do NOT undergo cyclic bleeding** (unlike endometriosis) - **Symptoms:** Menorrhagia, dysmenorrhea, pelvic pain before onset of menstruation --- ### Endometriosis - Presence of endometrial glands and stroma **outside** the endomyometrium - Affects ~10% of reproductive-age women; ~50% of women with infertility - **Common sites:** Ovaries, pouch of Douglas, uterine ligaments, tubes, rectovaginal septum; rarely lungs, heart, bone #### Theories of Aetiology - **Regurgitation theory** — menstrual backflow through fallopian tubes → implantation (most accepted) - **Metaplastic theory** — coelomic epithelium differentiates into endometrial tissue - **Vascular/lymphatic dissemination** — explains distant sites (lungs, skeletal muscle) #### Pathogenesis Key Points - Endometriotic tissue has increased prostaglandin E2 and high aromatase activity → increased local oestrogen → promotes survival and persistence of ectopic tissue - This explains why COX-2 inhibitors and aromatase inhibitors are beneficial treatments #### Morphology - Contains **functioning** endometrium → undergoes cyclic bleeding - Appears as red-brown nodules/implants on serosal surfaces - Ovarian involvement → large blood-filled **chocolate cysts** (old blood turns brown) - Widespread fibrosis, adhesions, sealed tubal fimbriated ends, distorted ovaries/oviducts - **Histologic diagnosis** requires at least 2 of 3: endometrial glands + endometrial stroma + hemosiderin pigment #### Clinical Features - Severe dysmenorrhea and pelvic pain (from intrapelvic bleeding and periuterine adhesions) - Infertility (from tubal/ovarian scarring) - Dyspareunia (uterine/bladder serosa involvement) - Pain on defecation (rectal wall involvement) - Dysuria (bladder serosa involvement) --- ### Abnormal Uterine Bleeding **Types:** Menorrhagia · Metrorrhagia · Postmenopausal bleeding - Bleeding without organic uterine lesion = **dysfunctional uterine bleeding** - **Four categories of causes:** **1. Failure of Ovulation (most common)** - Causes: hypothalamic-pituitary-adrenal/thyroid dysfunction, functional ovarian lesions (excess oestrogen), malnutrition, obesity, severe stress - Result: oestrogen excess without progesterone → endometrium stays in proliferative phase (no secretory phase) → prone to breakdown and bleeding **2. Inadequate Luteal Phase** - Corpus luteum fails to mature or regresses prematurely → relative progesterone deficiency - Endometrium fails to show expected secretory changes **3. Contraceptive-Induced Bleeding** - Older oral contraceptives → decidua-like stroma + inactive nonsecretory glands - Current pills no longer cause these changes **4. Endomyometrial Disorders** - Chronic endometritis - Endometrial polyps - Submucosal leiomyomata --- ### Endometrial Hyperplasia - Prolonged oestrogen excess without progestin counterbalance → exaggerated endometrial proliferation → important precursor to endometrial carcinoma - **Causes of oestrogen excess:** Anovulation (perimenopause), exogenous oestrogen therapy, oestrogen-secreting ovarian tumours, **obesity** (adipose tissue converts steroid precursors to oestrogens) #### Classification and Cancer Risk | Type | Carcinoma Risk | |---|---| | Simple hyperplasia without atypia | <1% | | Complex hyperplasia without atypia | <5% | | Complex hyperplasia WITH atypia | 20–50% | - Hyperplasia with atypia must be evaluated for cancer and monitored with serial endometrial biopsies - **PTEN tumour suppressor gene** — inactivating mutations are early events; PTEN normally brakes PI-3-kinase/AKT signalling; loss promotes progression to endometrial carcinoma - In time, hyperplasia may proliferate autonomously (no longer needs oestrogen) → carcinoma --- ### Endometrial Carcinoma - Appears between ages 55–65; uncommon before 40 - Most frequent cancer of female genital tract in developed countries (where cervical cancer prevalence is low) #### Two Distinct Types | Feature | Endometrioid (Type I) | Serous (Type II) | |---|---|---| | Frequency | 80% | ~15% | | Background | Oestrogen excess, hyperplasia | Endometrial atrophy | | Patient | Perimenopausal | Older postmenopausal | | Key mutations | PTEN, mismatch repair genes | TP53 (nearly all cases) | | Histology | Resembles normal endometrium; glands | Small tufts and papillae; high cytologic atypia | | Behaviour | Gradual | Aggressive (high-grade by definition) | | p53 IHC | Low | High (mutant p53 accumulates) | - **Endometrioid risk factors:** Obesity, diabetes, hypertension, infertility, unopposed oestrogen, tamoxifen use - Cowden syndrome (germline PTEN mutation) → high risk for endometrioid carcinoma - Coexistence with breast carcinoma more frequent than by chance (both oestrogen-dependent) - **Clinical features:** Leukorrhea + irregular/postmenopausal bleeding; slow to metastasize but eventually spreads to regional nodes and distant sites - **Prognosis:** Early-stage 5-year survival ~90%; drops sharply with higher stage; serous type prognosis depends heavily on operative staging and peritoneal washings --- ### Endometrial Polyps - Sessile, hemispheric lesions 0.5–3 cm; larger ones project into uterine cavity - Histology: Resembles endometrial basalis; frequently with small muscular arteries; glands often cystically dilated - Stromal cells are **monoclonal** — neoplastic component; often with rearrangement of chromosomal region 6p21 - Most common around menopause - Clinical significance: Abnormal uterine bleeding + rare but real risk of malignant transformation --- ### Leiomyoma (Fibroids) - Benign tumours of smooth muscle cells of the myometrium - **Most common benign tumour in females** — affects 30–50% of reproductive-age women; more frequent in Black women - Monoclonal; associated with recurrent chromosomal abnormalities (rearrangements of chromosomes 6 and 12) - Oestrogen-stimulated growth → shrink postmenopausally - **Locations:** - Intramural — within myometrium - Submucosal — beneath endometrium (most likely to cause bleeding) - Subserosal — beneath serosa; may develop parasitic blood supply from surrounding organs - **Morphology:** Sharply circumscribed, firm, grey-white, whorled cut surface; may be solitary or multiple; foci of fibrosis, calcification, degenerative softening - **Leiomyomas almost NEVER transform into sarcomas** — multiple lesions do not increase malignancy risk - **Symptoms:** Often asymptomatic (found incidentally); most frequent sign is **menorrhagia ± metrorrhagia**; large ones cause dragging sensation --- ### Leiomyosarcoma - Arise **de novo** from mesenchymal cells of myometrium — NOT from pre-existing leiomyomas - Almost always solitary; most often in postmenopausal women (opposite of leiomyoma) - **Morphology:** Soft, haemorrhagic, necrotic masses - **Diagnostic features of malignancy (all three needed):** - Tumour necrosis - Cytologic atypia - Mitotic activity - Well-differentiated tumours at the borderline are called **smooth muscle tumours of uncertain malignant potential** - Recurrence after removal is common; metastases typically to lungs - **5-year survival ~40%**; anaplastic tumours carry worse prognosis --- ## 4. Disorders of the Fallopian Tubes and Ovaries **Conditions covered:** Salpingitis · Tubal Carcinoma · Follicle & Luteal Cysts · PCOS · Ovarian Tumours (Surface Epithelial · Germ Cell) --- ### Fallopian Tube Disorders #### Salpingitis - Most common disorder of fallopian tubes; almost always a component of PID - **Causative organisms:** With declining gonorrhoea incidence, nongonococcal organisms now dominate — Chlamydia, Mycoplasma hominis, coliforms, streptococci, staphylococci (postpartum) - Tuberculous salpingitis — rare; almost always combined with tuberculous endometritis - **Complications:** - Tuboovarian abscess / tuboovarian complex (when infection subsides) - Adhesions of tubal plicae → increased risk of **tubal ectopic pregnancy** - Damage/obstruction of tubal lumina → **permanent sterility** - Nongonococcal infections can penetrate tube wall → blood-borne spread to meninges, joints, heart valves - **Clinical features:** Fever, lower abdominal/pelvic pain, pelvic masses from tube distention #### Fallopian Tube Carcinoma - Primary adenocarcinomas — serous or endometrioid type - Increased in women with **BRCA mutations** — 10% of prophylactic oophorectomy specimens in BRCA mutation carriers had occult malignancy, equally split between ovary and fallopian tube (usually at fimbria) - Frequently involve omentum and peritoneal cavity at presentation (due to access to peritoneal cavity) --- ### Follicle and Luteal Cysts - So common they may be considered variants of normal physiology - Originate from unruptured graafian follicles or follicles that ruptured and immediately resealed - Usually small (1–1.5 cm), filled with clear serous fluid; occasionally up to 4–5 cm causing palpable mass and pelvic pain - Lined by granulosa or luteal cells; pressure atrophy of lining cells as fluid accumulates - **Complication:** Rupture → intraperitoneal bleeding and acute abdomen --- ### Polycystic Ovarian Disease (PCOS) - Multiple cystic follicles producing excess androgens and oestrogens - Presents after menarche with: **oligomenorrhea, hirsutism, infertility, obesity** - **Gross:** Ovaries twice normal size, grey-white with smooth outer cortex, subcortical cysts 0.5–1.5 cm - **Histology:** Thickened fibrotic ovarian capsule; innumerable cystic follicles lined by granulosa cells with hyperplastic luteinized theca interna; **conspicuous absence of corpora lutea** - **Biochemical abnormalities:** Excess androgens + high LH + low FSH - Mechanism: Ovaries elaborate excess androgens → converted to oestrogens in peripheral fat → inhibit FSH secretion via hypothalamus → no follicle maturation → no ovulation --- ### Tumours of the Ovary **Three cell types giving rise to ovarian tumours:**
Answer: Model answer pending
Answer: Model answer pending
Answer: **General risk factors for ovarian cancer:** - Nulliparity, family history, BRCA1/BRCA2 mutations - BRCA1 carriers → ~30% lifetime risk; BRCA2 carriers → lower risk - Prolonged oral contraceptive use → reduces risk #### Surface Epithelial Tumours **Origin:** Coelomic epithelium; with repeated ovulation, surface epithelium becomes entrapped in cortex → forms epithelial cysts → neoplastic transformation **Categories:** - Benign: usually cystic (cystadenoma) ± stromal component (cystadenofibroma) - Borderline: low malignant potential — low-grade with limited invasive potential; better prognosis - Malignant: cystic (cystadenocarcinoma) or solid (carcinoma) ##### Serous Tumours - Most common ovarian epithelial tumour - 60% benign · 15% borderline · 25% malignant - Benign: ages 30–40; malignant: ages 45–65 - Together, borderline + malignant serous = most common ovarian malignancies (~60% of ovarian cancers) - **Two types of serous carcinoma:** - **Low-grade** — arise from benign/borderline lesions; stepwise progression; KRAS, BRAF, or ERBB2 mutations - **High-grade** — develop rapidly; may arise from tubal intraepithelial carcinoma; **96% have TP53 mutations**; also Notch signalling pathway and FOXM1 mutations - **Morphology:** - Large, spherical-ovoid cystic structures up to 30–40 cm - 25% of benign tumours are bilateral - Papillary projections more prominent in malignant tumours - Histology: tall columnar ciliated cells lining cysts; **Psammoma bodies** (concentrically laminated calcified concretions) common at papillary tips — characteristic finding - Malignant: complex multilayered papillae, anaplasia, stromal invasion - **Prognosis:** Confined to ovary → ~70% 5-year survival; penetrated capsule → <15% 10-year survival; borderline → nearly 100% survival ##### Mucinous Tumours - Similar to serous but lined by mucin-secreting cells - 80% benign · 10% borderline · 10% malignant (much less likely to be malignant than serous) - More likely to be larger and multicystic; much less likely to be bilateral - **Pseudomyxoma peritonei** — implantation of mucinous cells in peritoneum with copious mucin production; most cases caused by metastasis from GI tract (primarily appendix), not ovarian primary - **Krukenberg tumour** — metastatic mucinous adenocarcinoma from GI tract (often bilateral) — bilateral involvement helps differentiate from primary ovarian mucinous tumour - Prognosis better than serous counterpart; stage is major determinant of outcome ##### Endometrioid Tumours - May be solid or cystic; sometimes develop in association with endometriosis - Histology: tubular glands resembling endometrium lining cystic spaces - Usually malignant; bilateral in ~30% of cases - **15–30% of women have concomitant endometrial carcinoma** — important clinical point - PTEN mutations — similar to endometrioid endometrial carcinoma ##### Brenner Tumour - Uncommon, solid, usually unilateral - Abundant stroma containing nests of **transitional-type epithelium resembling urinary tract epithelium** - Smoothly encapsulated, grey-white, ranges from a few cm to 20 cm - Most are benign; borderline and malignant forms exist --- #### Germ Cell Tumours — Teratomas - 15–20% of ovarian tumours - Arise in first 2 decades of life; **younger patient = greater likelihood of malignancy** - >90% are benign mature cystic teratomas; immature malignant variant is rare ##### Benign (Mature) Cystic Teratoma — Dermoid Cyst - Contain mature tissues from all 3 germ cell layers (ectoderm, endoderm, mesoderm) - Usually cysts lined by epidermis with adnexal appendages → **dermoid cysts** - Filled with sebaceous secretion and matted hair; may contain teeth, bone, cartilage, bronchial/GI epithelium - ~90% unilateral (right side more common); rarely >10 cm - Found in young women as ovarian masses or incidentally on imaging (calcification from tooth-like structures) - **Complications:** - Torsion (10–15% of cases) → acute surgical emergency - Infertility (unknown mechanism) - Limbic encephalitis (rare paraneoplastic complication) — remits with tumour resection - Malignant transformation in ~1% (usually to SCC) ##### Immature Malignant Teratoma - Mean age at detection: **18 years** - Bulky, predominantly solid, areas of necrosis; occasionally cystic foci - Histology: presence of **immature elements** — minimally differentiated cartilage, bone, muscle, nerve - **Neuroepithelial differentiation** particularly ominous — aggressive and widely metastasizing - Graded and staged: Grade I, Stage I often curable; higher grade/stage = guarded prognosis ##### Specialized Teratomas - **Struma ovarii** — composed entirely of mature thyroid tissue; may produce **hyperthyroidism**; small, solid, unilateral, brown - **Ovarian carcinoid** — may produce carcinoid syndrome (rare) --- #### Clinical Correlations — Ovarian Tumours - Symptoms usually appear only when tumours are **well advanced** → management is challenging - 30% of ovarian neoplasms discovered incidentally on routine gynaecologic examination - Large masses → increased abdominal girth; smaller masses (dermoid cysts) → torsion → acute abdomen - Functioning tumours → present with endocrinopathies; serous tumours → ascites from peritoneal seeding - **CA-125** — elevated in 75–90% of women with epithelial ovarian cancer; BUT undetectable in up to 50% of cancers limited to ovary; elevated in benign conditions too → limited screening value; **most useful for monitoring treatment response** --- ## 5. Diseases of Pregnancy **Conditions covered:** Placental Inflammations & Infections · Ectopic Pregnancy · Gestational Trophoblastic Disease · Preeclampsia/Eclampsia --- ### Placental Inflammations and Infections **Two routes of infection:**
Answer: - Histology: neutrophilic infiltration of chorioamnion + oedema + congestion = **acute chorioamnionitis** - Extension → umbilical cord and villi → **funisitis** (acute vasculitis of cord) - Organisms: Mycoplasma, Candida, vaginal bacteria
Answer: - Organisms: Syphilis, TB, Listeria, Toxoplasma, Rubella, CMV, HSV → **TORCH complex** (Toxoplasmosis, Other, Rubella, CMV, Herpes) - Can affect foetus → congenital infections --- ### Ectopic Pregnancy - Implantation of fertilized ovum anywhere other than the uterus - ~1% of all pregnancies - **>90% are tubal pregnancies**; other sites: ov