Patho Chapter 33

Enterocele

Herniation of the rectouterine pouch into the rectovaginal septum Congenital or acquired

Breast Cancer: Physical Activity

-May reduce overall risk of breast cancer -May reduce the invasiveness of breast cancer -Sedentary lifestyle may increase risk *Increased insulin resistance *Inflammation *Decreased immune function

Cervical cancer

-Almost always associated with HPV infection *Causes high-grade dysplasia and cancer =Cervical intraepithelial neoplasia (CIN) and cervical carcinoma in situ (CIS) *Ability of HPV to act as a carcinogen depends on the viral proteins E6 and E7 =Interfere with activity of tumor suppressor proteins *Other risk factors include multiple sexual partners, young age at first sexual intercourse, high parity, immunosuppression, oral contraceptives, use of nicotine -Progresses slowly *Normal cervical epithelial cells to dysplasia to carcinoma in situ and, eventually, invasive cancer -Predominantly asymptomatic -Pap and HPV testing -Treatment based on neoplastic change, size and location of lesion, extent of metastasis

Secondary amenorrhea

-Absence of menses after previous menstrual periods -Common in early adolescence, pregnancy, lactation, and during perimenopause *Anovulation -Also associated with thyroid disorders, hyperprolactinemia, excessive stress or weight loss, and polycystic ovary syndrome -Pregnancy must be ruled out before any further evaluation

Pelvic inflammatory disease (PID)

-Acute inflammatory process caused by infection -May involve any organ of the upper genital tract *Entire pelvic cavity in severest form -Sexually transmitted diseases migrate from the vagina to the upper genital tract (usually chlamydia and gonorrhea) -Associated with multiple sexual partners, previous PID, douches, IUD for birth control -Salpingitis (inflammation of fallopian tubes) *Inflammatory process induces changes in the columnar epithelium that line the upper reproductive tract =Localized edema =Necrosis *Gonorrhea gonococci attaches to fallopian tubes *Chlamydia enters the tubal cells and replicates, bursting the cell membrane as it reproduces, causing permanent scarring -May cause infertility and tubal obstruction, ectopic pregnancy, pelvic pain, and intestinal obstruction -Manifestations vary from no pain to sudden severe abdominal pain with fever -Symptoms often vague -Rapid empiric treatment to prevent complications

Abnormalities of the Female Reproductive Tract

-Androgen insensitivity syndrome *Disorder of hormone resistance due to mutations in androgen receptor *May result in female phenotype despite male genotype =Testes produce normal concentrations of androgens =Absence of cervix, uterus, and ovaries =May have short vagina that ends blindly =Mild forms with less dramatic phenotypic manifestations -Uterine abnormalities *Most stem from abnormal cell migration in the müllerian ducts during key moments in fetal development *Rarely diagnosed until difficulty with getting pregnant or carrying fetus to term -Lower genital tract abnormalities *Two vaginas *Vaginal septum

Proliferative breast lesions with atypia

-Atypical hyperplasia *Increase in the number of cells or proliferation and the cells have some variation in structure *Atypical ductal hyperplasia =Abnormal proliferating cells in breast ducts *Atypical lobar hyperplasia =Proliferation of cells in the lumen of lobular units -Associated with increased risk of breast cancer *The younger a woman is when diagnosed with atypical hyperplasia, the higher the risk that breast cancer will develop

Endometrial Polyps

-Benign mass of endometrial tissue -Structurally diverse *Hyperplastic (Stalk mushroom like) *Atrophic (Inactive) *Functional -Intermenstrual bleeding; excessive bleeding can occur. Malignancy rare

Benign Growths and Proliferative Conditions

-Benign ovarian cysts *Unilateral *Produced when a follicle or number of follicles are stimulated but no dominant follicle develops and reaches maturity *Cysts can cause ovarian torsion (sufficiently large cyst that twists the ovary on its ligament and decrease blood supply, cause extreme pain. Medical emergency) (rare) *Follicular cysts =Fluid-filled cyst caused when dominant follicle fails to rupture or one or more of the nondominant follicles fail to regress *Corpus luteum cysts =Highly vascularized cyst formed by the granulosa cells left behind after ovulation Can rupture and cause hemorrhage *Dermoid cysts =Ovarian teratomas that contain elements of all three germ layers (have hair, bone, muscle fibers, sweat glands) =Have malignant potential

Cancer

-Cervical cancer -Vaginal cancer -Vulvar cancer -Endometrial cancer -Ovarian cancer

Proliferative breast lesions without atypia(deviation from the normal)

-Characterized by proliferation of ductal epithelium or stroma, or both, without cellular signs of abnormality -Usual ductal hyperplasia *Additional or proliferating epithelial cells that fill and distend the ducts and lobules. Benign cells. -Intraductal papillomas *Solitary papillomas: monotonous papillary cells that grow in wall of cyst into lumen *Diffuse papillomatosis:multiple papillomas, min of 5. *Can harbor areas of atypia requiring surgical excision -Sclerosing adenosis *Lobular lesion with increased fibrous tissue and scattered glandular cells, increased chance of cancer. -Radial scar *Irregular, radial proliferation of ductlike small tubules entrapped in a dense central fibrosis -Simple fibroadenomas *Benign solid tumors that contain glandular and fibrous lesions. Influence risk of breast cancer if proliferative, not simple

Vulvodyniavestibulitis

-Chronic vulvar pain without visible dermatosis; inflammation of the vulva or vaginal vestibule, or both; infection; neoplasia; or identifiable neurologic disorder -Classified based on pain *Localized *Generalized *Provoked or unprovoked *Mixed -Unknown cause—likely multifactorial -Few treatment options

Breast Cancer: Oral contraceptives

-Combined estrogen-progestogen oral contraceptives (OCs) increase the risk for breast, cervix, and liver cancers

Leiomyomas

-Commonly called myomas or uterine fibroids (Scar tissue) -Benign tumors of smooth muscle cells in the myometrium *Estrogen- and progesterone-sensitive *Classified as subserous, submucous, or intramural -Cause abnormal uterine bleeding, pain, and symptoms related to pressure on nearby structures

Uterine prolapse

-Descent of the cervix or entire uterus into the vaginal canal or completely through the vagina *Grade 1: Not treated unless it causes discomfort *Grade 2 and 3: Cause feelings of fullness, heaviness, and collapse through the vagina -Pessary *Removable mechanical device that holds the uterus in position *Kegel exercises *Estrogen therapy *Surgery is treatment of last resort

Breast Cancer: Environmental chemicals

-Difficult to link to breast cancer *Must consider life history of chemical exposure -Xenoestrogens *Synthetic chemicals that mimic the actions of estrogens *Found in many pesticides, fuels, plastics, detergents, and drugs *May contribute to breast cancer

Breast Cancer: Environmental factors

-Environmental causes of breast cancer possibly affect the breast the most during critical phases of development *Mitotic activity and cell division are greater than they are later in life

Primary amenorrhea

-Failure of menarche and absence of menstruation by age 13 without development of secondary sex characteristics or by age 15 regardless of presence of secondary sex characteristics -Compartment disorders *I—Anatomic defects: absence of vagina or uterus *II—Involve the ovary, genetic disorders, and androgen insensitivity syndrome AIS lack of estrogen *III—Involve anterior pituitary gland and result in failure of hormonal signaling to ovaries *IV—CNS disorders, primarily hypothalamic defects -Treatment to correct underlying disorder

Breast Cancer: Prolactin and growth hormone

-GH induces the production of IGFs in the liver; IGF signaling is important for breast development and is implicated in breast carcinogenesis

Disorders of the Female Breast

-Galactorrhea *Persistent and sometimes excessive secretion of milky fluid from the breasts of a woman who is not pregnant or nursing (Hormone imbalances of hypo-thalamic pituitary gland) =Can also occur in men *Nonpuerperal hyperprolactinemia =Excessive amounts of prolactin in the blood not related to pregnancy or childbirth =Associated with certain drugs, hypothyroidism, and pituitary tumors *Women with galactorrhea also experience menstrual abnormalities

Breast Cancer: Inherited cancer syndromes, genes, epigenetic considerations

-Genetic heterogenicity (genetic profile) -Risk of breast cancer increases with number of first-degree relatives affected *BRCA1 (breast cancer 1 gene) =Located on chromosome 17 =Tumor-suppressor gene =Carriers are at higher risk for breast and ovarian cancer *BRCA2 (breast cancer 2 gene) =Located on chromosome 13 =More likely in men who develop breast cancer

Breast Cancer: Insulin and insulin-like growth factors

-IGFs regulate cellular functions involving cell proliferation, migratory, differentiation, and apoptosis -Insulin therapy and sulfonylurea were found to be mildly associated with increased breast cancer risk

Breast Cancer: Obesity

-Increases cancer risk from cellular pathways that involve hormonal regulation, cellular proliferation, and immunity *Associated with a reduced risk of premenopausal breast cancer -Associated with poor survival among women with breast cancer

Impaired Fertility

-Infertility *Inability to conceive after 1 year of unprotected intercourse *Female infertility results from dysfunction of the normal reproductive process =Menses and ovulation =Fallopian tube function =Implantation of fertilized egg *Initial workup includes semen analysis, determination of ovulation, and hysterosalpingography of the fallopian tubes *Treatment aimed toward correction of problems identified

Bartholinitis

-Inflammation of one or both ducts that lead from the vaginal opening to the Bartholin glands -Caused by microorganisms that infect the lower female reproductive tract -Inflammation narrows the distal portion of the ducts -Leads to obstruction and stasis of glandular secretions -Treated with antibiotics

Cervicitis

-Inflammation of the cervix:must have 2 different diagnostic signs, purulent or mucopurulent discharge, or endocervical bleeding from gentle cotton swab. -Infectious or noninfectious cause *Chemicals and substances introduced into the vagina *Disruptions in the normal vaginal flora -Mucopurulent cervicitis *Caused by one or more sexually transmitted pathogens *Mucopurulent exudate drains from the external cervical os *Symptom of PID *Treat with antibiotics

Breast Cancer: Radiation

-Ionizing radiation is a known mutagen and established carcinogen for breast cancer *Accidentally or medically induced radiation *Women treated with chest radiation for a pediatric or young adult cancer have a substantially increased risk of breast cancer

Vaginitis

-Irritation/inflammation infection of the vagina -Sexually transmitted pathogens, overgrowth of normal flora, and Candida albicans -Acidic nature of the vagina provides some protection *Maintained by cervical secretions and normal flora *Altered by douching, soaps, spermicides, feminine hygiene sprays, deodorized pads or tampons, pregnancy, and diabetes -Treatment to develop and maintain acidic environment; administration of antimicrobials or antifungals; symptom relief

Adenomyosis

-Islands of endometrial glands surrounded by benign endometrial stroma within the myometrium (looks like hunks of cheese) -Asymptomatic or abnormal bleeding, dysmenorrhea, uterine enlargement, and tenderness

Sexual Dysfunction

-Lack of satisfaction with sexual function resulting from pain or a deficiency in sexual desire, arousal, or orgasm/climax -Organic and/or psychosocial -Disorders of desire *Most common sexual dysfunction in women *Increases with age -Anorgasmia *Inability of a woman to reach or achieve orgasm -Dyspareunia *Pain at any time from the beginning of arousal to after intercourse *Psychosocial and organic causes -Vaginismus *Involuntary muscle spasm in response to attempted penetration

Ductal carcinoma in situ (DCIS)

-Limited to breast ducts and lobules without invasion of the basement membrane -Does not appear to progress from sequential steps of low grade to higher grades *Most lesions of DCIS will not evolve to invasive cancer -Identified on mammography *Detection and treatment of nonpalpable DCIS often overdiagnosed and overtreated

Breast Cancer: Manifestations and Treatments

-Manifestations: *Painless lump *Palpable nodes in axilla *Dimpling of skin *Edema *Bone pain -Treatment: *Based on stage of cancer *Surgery *Radiation *Chemotherapy *Hormone therapy *Biologic therapy

Abnormal uterine bleeding

-Menstrual irregularity -Dysfunctional uterine bleeding *Heavy or irregular bleeding in the absence of organic disease *Associated with lack of ovulation *Usually perimenopausal (age 40-50) *Can lead to iron deficiency anemia and associated symptoms *Treated with NSAIDs, oral hormonal contraceptives, levonorgestrel intrauterine device, ablation, or hysterectomy

Breast Cancer: Pathogenesis

-Most adenocarcinomas -Arise from the ductal/lobular epithelium as carcinoma in situ *Proliferation of epithelial cells that is confined to the ducts and lobules -Infiltrating (invasive) ductal type *Tumors stay small but metastasize early *70% of breast cancers -Heterogeneous *Diverse molecular, biologic, phenotypic, and pathologic changes

Endometrial cancer

-Most common type of uterine cancer and gynecologic malignancy -Primary risk factor is unopposed estrogen exposure (no progesterone) *Leads to endometrial hyperplasia -Associated with type 2 diabetes -Usually occurs in postmenopausal women -Manifested by abnormal vaginal bleeding

Breast Cancer

-Most frequently diagnosed cancer in women, most common cancer in American women. -Leading cause of death in women ages 40-44 -Risk related to timing, duration, and pattern of exposures -Reproductive factors: Pregnancy *Reduced risk if pregnancy at young age *Pregnancy-associated breast cancer =Breast cancers that occur during pregnancy and risk may persist to at least 5 years postpartum and longer *Delayed child bearing will show rise in breast cancer. *Lifetime risk is higher is nulliparous women than parous women -Lobular involution and age and postlactational involution *Terminal duct lobular units =Predominant source of breast cancers =Lobular involution +Associated with reduced risk of breast cancer =Postlactational involution (regress) +Mammary gland regresses and remodels to its prepregnant state

Lobular carcinoma in situ (LCIS)

-Originates from the terminal duct-lobular unit -Cells grow noncohesively due to a loss of the tumor-suppressive adhesion protein E-cadherin -Found as an incidental lesion from biopsy *Not associated with calcifications or stromal reactions that produce mammographic densities -Risk factor for invasive carcinoma

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)

-PMDD considered a severe, sometimes disabling extension of PMS -Cyclic physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usual activities -Occurs in luteal phase of the menstrual cycle -Multiple theories to explain causes/symptoms *Hormones *Genetics *Environmental -Symptomatic treatment

Infection and Inflammation

-Pelvic inflammatory disease (PID) -Vaginitis -Cervicitis -Vulvodyniavestibulitis -Bartholinitis

Endometriosis

-Presence of functioning endometrial tissue or implants outside the uterus -Responds to hormone fluctuations of the menstrual cycle -Possible causes *Coelomic metaplasia *Retrograde menstruation *Embryonic cell rest *Iatrogenic mechanical transplantation *Lymphatic and vascular dissemination *Genetic predisposition -Highly associated with infertility -Dyschezia (pain on defecation) is hallmark symptom -Treatment to prevent progression, alleviate pain, and restore fertility

Hormonal and Menstrual Alterations

-Primary dysmenorrhea *Painful menstruation associated with prostaglandin release in ovulatory cycles (beginning of cycle) =Excessive prostaglandin F2α +Increased myometrial contractions +Constricted endometrial blood vessels +Increased nerve hypersensitivity -Secondary dysmenorrhea *Related to pelvic pathology *May occur any time in the menstrual cycle -Dysmenorrhea *Chief symptom is pelvic pain associated with onset of menses *NSAIDs for pain *May be relieved with hormonal contraceptives -Primary amenorrhea -Secondary amenorrhea -Abnormal uterine bleeding -Polycystic ovary syndrome] -Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)

Breast Cancer: Diet

-Prospective epidemiologic studies on diet and breast cancer risk fail to show an association that is consistent, strong, and statistically significant except for alcohol intake, being overweight, and weight gain after menopause

Alterations of Sexual Maturation

-Puberty *Development of secondary sex characteristics *Rapid growth *Ability to reproduce *Age of onset is multifactorial—typically ages 8-13 years -Delayed or absent puberty *Delayed puberty is normal in about 95% of cases *Other 5% caused by disruption of hypothalamic-pituitary-gonadal axis or systemic disease -Precocious puberty *Sexual maturation before age 6 in black girls and age 7 in white girls *Sexual maturation before age 9 in boys *Multifactorial =Obesity (and delayed, depends on reason for obesity) =Increased protein consumption =Effects of common household products =Lethal CNS tumors

Breast Cancer: Mammographic breast density

-Radiologic appearance of the breast, reflecting variations in breast composition. *Higher MBD, higher risk of cancer. Strong and consistent risk factor for breast cancer

Vaginal cancer

-Rare -Usually squamous cell carcinoma *Associated with high-risk HPVs

Ovarian cancer

-Responsible for more deaths than all other gynecologic malignancies combined -Risk reduced by factors that suppress ovulation -Three ovarian cell types: *Germ cells 3%-5% *Endocrine and interstitial hormone- *producing cells 7% *Epithelial cells 90% =Benign and malignant tumors come from each of the three ovarian cell types -Usually no early symptoms *Advanced cancer when caught -Surgery to remove tumor

Breast Cancer: Hormonal factors

-Six factors that affect risk of breast cancer: *Protective effect of an early (i.e., in the 20s) first pregnancy *Protective effect of removal of the ovaries and pituitary gland *Increased risk associated with early menarche, late menopause, and nulliparity *Relationship between types of fat, free estrogen levels, and oxidative changes in estrogen metabolism *Hormone-dependent development and differentiation of mammary gland structures *Efficacy of antihormone therapies for treatment and prevention of breast cancer -Vast majority of breast cancers are initially hormone dependent *Estrogens play prominent roles in cellular proliferation, differentiation, and apoptosis *Androgen receptor (AR) has been implicated in prostate cancer and now in the development and progression of breast cancer -Hormone replacement therapy and breast cancer risk: estrogen plus progesterone therapy (MHT) and estrogen-only therapy (ET) *Estrogen-progestogen menopausal therapy and estrogen-progestrogen contraceptives are carcinogenic agents for breast cancer

Benign Breast Disease

-Spectrum of noncancerous changes in the breast -Most common symptoms are pain, palpable mass, or nipple discharge -Broadly classified *Nonproliferative breast lesions *Proliferative breast disease without atypia *Atypical (atypia) hyperplasia

Pelvic Organ Prolapse

-The bladder, urethra, and rectum are supported by the endopelvic fascia and perineal muscles -The muscular and fascial tissue loses tone and strength with aging -Fails to maintain organs in proper position -Associated with aging, obesity, and hysterectomy

Polycystic ovary syndrome

-Two of the following: *Few or anovulatory menstrual cycles *Elevated levels of androgens *Polycystic ovaries -Associated with genetic predisposition and obesity *Insulin resistance *Excessive insulin and androgens -Symptoms related to anovulation and hyperandrogenism (DUB or amenorrhea, hirsutism, acne, infertility, obesity) -Treated with oral contraceptives

Nonproliferative breast lesions

-Usually not associated with an increased risk of breast cancer -Simple breast cysts *Fluid-filled sacs *Often rupture with release of secretory material into the adjacent tissue resulting in chronic inflammation and scarring fibrosis -Papillary apocrine change *Increase in ductal epithelial cells that has apocrine changes or an eosinophilic cytoplasm -Mild hyperplasia of the usual type *Increase in the number of epithelial cells within a duct that is more than two but not more than four cells in depth

Vulvar cancer

-Usually squamous cell carcinoma -Associated with HPV, increasing age, previous cancer, autoimmune conditions, and immunosuppression

Rectocele

Bulging of the rectum and posterior vaginal wall into the vaginal canal Genetic and familial predisposition

Cystocele

Descent of a portion of the posterior bladder wall and trigone into the vaginal canal (bladder in front of uterus) Associated with childbirth