Pathology of the reproductive systems. Pathology of the breast V. Žampachová I. PAÚ LF MU Male genital system • Prostatitis, benign prostatic hyperplasia • www.nature.com > Prostatitis •Bacterial (acute purulent) •Systemic symptoms, dysuria, frequency, local pain •Ascending infection in UTI (urinary tract infection) •Iatrogenic (cathetrisation, surgery, …) •ATB therapy • •Chronic prostatitis/ chronic pelvic pain syndrome •Most common (90%) •Recurrent chronic genitourinary pain •Sexual dysfunction • Benign prostatic hyperplasia •epidemiologic factors: •age (BPH prevalence rising with age, 70% by age 60, 90% by 80) •geographic/racial (low in Asia, more common in W Europe) • •pathogenesis: •not completely clear •hormonal dysbalance •Gross: nodular hyperplasia •periurethral (transition zone) mostly affected→ urethral compression + obstruction • Benign prostatic hyperplasia • •Clinical signs + complications: partial → complete urethral obstruction, urinary residuum, risk of infection lower urinary tract symptoms (disturbances of the urine flow) •Storage symptoms – nocturia, frequency, urgency •Voiding symptoms – weak stream •acute/chronic urinary retention, bladder trabecular hypertrophy, cystitis •+ ascending infection – pyelonephritis, •Hydronephrosis. •Benign, but setting for possible preneoplastic changes •Th: surgery, drugs Image055 Complications of prostatic hyperplasia Image053 Benign prostatic hyperplasia Benign prostatic hyperplasia - implications •Urination more than every 2 hours •More than once during the night •Weak, interrupted urine stream •Difficulty emptying the bladder •Genital/pelvic pain •Pain associated with intercourse •Urine leakage •Possible pelvic floor disorder • Prostatic cancer •↑ incidence •1st – 3rd of the most common male malignancies (prostate – lungs – colorectal) • •peripheral zone of prostate, dorsal part (palpation per rectum- digital rectal examination) • •dg.: •needle biopsy (by suspicion – nonspecific signs, general screening questioned) •transurethral resection ( BHP treatment – incidental) •Spread: regional LN, bones (!diff. dg. of pain x local mechanic origin) Prostatic cancer •Risk factors: •Age •African American •Family history •High-fat diet •Alcohol consumption •Protective factors: •Physical activity •Tomato (lycopene) • Prostatic cancer •Staging/grading important for therapy method choice •Low grade tumors in older males/limited survival expectations – observation – watchful waiting •Any tumor in younger males – therapy •Surgery •Radiation •Hormone therapy (androgen deprivation) •Chemotherapy •Age ˃ 50 years + unknown cause of musculoskeletal pain + past history of prostatic cancer: suspicion!! • Prostatic cancer therapy complications •Urinary incontinence (may be temporal) •Impotence/sexual dysfunction •Rectal injury with fecal incontinence, diarrhea •Muscle atrophy, osteoporosis • •Pelvic physical therapy necessary – pre- + postoperative Prostatic arcinoma (dorsal, blue) + benign hyperplasia (central) Image056 Prostatic cancer Prostatic cancer – spine metastases Disorders of the testes •Congenital defects •cryptorchidism (undescended testis) – infertility, ↑ risk of testicular cancer •Inflammation: orchitis/epididymitis, mostly bacterial (in UTI, sepsis) •Epididymis >>> testis •Viral (mumps) → possible infertility •Testicular torsion: sudden onset of severe scrotal pain, without immediate surgery → necrosis (haemorrhagic infarction due to twisting of vessels) – ! emergency • • • Testicular tumors •Germ cell tumors • •Testicular enlargement, firm consistency, may be painful •Regular testicular self-examination •Metastasis •Regional (retroperitoneal) lymph nodes •Lung, liver •Bones – late metastasis (pain) • • • • Germ cell tumors •~90 % of primary testicular tumors •Most common solid organ tumors in young males (15-35 years) •Classification: •Seminoma: 4th decade, good prognosis, combined therapy •Non-seminomatous tumors: variable types – variable age; different prognosis •Serum tumor markers: •detection in serum, tissues •important in diagnosis, monitoring the response to therapy, patient check-up after therapy • • Germ cell tumors •Prognosis: early detection (stage I, limited to the testis) – 95% cured •Therapy: combination of surgery (orchiectomy, LN dissection) + radiotherapy, chemotherapy •Implications: •Possible lymphedema, infertility + sexual dysfunction •Side effects + toxicity of chemo/radiotherapy •Second malignancy possible • • • Germ cell tumors Characteristics • age laboratory serum marker •Seminoma 30-50 10% HCG • •Embryonal 20-30 90% HCG/AFP •carcinoma •Yolk sac <3 90% AFP •Choriocarcinoma 20-30 100% HCG •Teratoma no predilection possible HCG,AFP •Mixed tu 15-30 possible HCG,AFP Penile disorders •Inflammations •balanoposthitis (glans + inner surface of the prepuce) •STD (gonorrhoea, genital herpes, syphilis …) •risk factors: •phimosis, chronic mechanical/chemical irritation •Immunodeficiency (DM) - candidiasis • Penile disorders •Benign epithelial tumors •condyloma accuminatum – viral wart • HPV 6, 11 • •Malignant epithelial tumors •invasive squamous cell carcinoma •geography (Latin America, East Asia) •circumcision - protective factor (↓HPV, carcinogenes in smegma) •risk factor – smoking, occupational (mineral oil, tar) •Macro: non-healing red patch, ulcer, verruca • Penile disorders •Erectile dysfunction: impotence •Risk factors: age, smoking, medical history (DM, heart disease, hypertension, obesity, alcoholism, local surgery, drugs •Causes: organic (neurogenic, venogenic, arteriogenic) x psychogenic (more common in young) •Sensitive situation /questions, diagnosis necessary •Treatment: pharmacology, prosthetic devices, pelvic floor exercises • Female genital tract • Menopause •1 year without menses •Perimenopause: hormonal decline, menstrual cycle irregularity •Physiological changes: reduced hormones‘ level incl. growth hormone, changes in tissue responsiveness mainly to estrogen throughout the body (skin, bone, muscles, heart, intestinal tract, blood vessel, brain, bladder) • Menopause •Clinical signs: •Thermoregulatory + vasomotor changes (hot flashes, night sweats) •Sleep disturbances •Anxiety, mood swings, irritability •Fatigue •Pain: headache, peripheral and/or spinal joint pain •Vaginal atrophy, infections •Sexual dysfunction •Pelvic floor dysfunction / prolapse • • • Menopause •Musculoskeletal system changes •Muscle mass decline, slower repair •Osteoporosis: ↑ resorption →↓ bone mass (density); risk factors: smoking, low calcium + vitamin D; beneficial: exercise •↑ peripheral (periostal) bone growth – part of osteoarthritis •↑ fracture risk •Kyphosis – spinal deformity Menopause •Medical management: •Hormone replacement therapy: decreasing benefits + increasing risk with the HRT duration + postmenopausal age (thrombosis, hormone-sensitive cancers, stroke) •Alternative + complementary therapy: individual results possible; not significant benefits in studies Menopause – implications for the terapists •Regular physical activity (↓ the risk for weight gain, fat distribution) •Moderate-intensity: reduction of osteoporosis, cardiovascular disease, sleep disturbances •Resistance training: reduction of muscle loss (+ adequate nutrition) •Pelvic floor muscle rehabilitation Genital tract infections •Genital tract – open to the outside, barriers necessary •Barrier function - vaginal flora, endocervical mucus; during fertile age •Predisposing factors – nonexistent barrier (age), barrier defect (loss of protective vaginal flora, menstruation, abortion, delivery + residua, instrumentation and other mucosal microtraumata, systemic diseases, drugs,…) • Genital tract infections •Ascending infection most usual (sexually transmitted disease/infection – STD/STI; G- fecal bacteria – E. coli, Proteus,…) •Lower genital tract (STD – HSV, molluscum contagiosum, HPV, trichomonas, chancroid, granuloma inguinale; endogenous – candida) •Entire genital tract (STD – gonorrhea, chlamydia, mycoplasma, syphilis; endogenous – enteric bacteria), may end in pelvic inflammatory disease • Sexually Transmitted Infections •Sexually Transmitted Disease - STD •Infection transmitted through vaginal, anal or oral sex •Every sexually active individual is at risk •Women acquire infections from men more than men from women •2/3 of STD occur in people under 25 yrs of age •Infection by multiple agents common (↑ risk) •Fetus or infants – vertical transplacental or perinatal transmission of STD → abortus, inborn defects, neonatal infection. Diagnosis + treatment!! Genital warts •May be asymptomatic; single or multiple painless cauliflower-like growths on the vulva, vagina, perineum, urethra, cervix, anus •Productive infection – low risk types (6, 11) •Other subtypes of HPV (i.e. 16, 18) strongly associated with cervical dysplasia and/or carcinoma •HPV - higher risk of vaginal, vulvar, penile, anal dysplasia/carcinoma •Some types in oral/laryngeal carcinoma •Vaccination preferably before start of sexual activity; males + females, 2 doses sufficient STI - complications gyn-PID-sch-transm03 Pelvic inflammatory disease •Infection + inflammation of upper genital tract (endometritis, salpingitis – fallopian tube inflammation, tuboovarian abscess, pelvic peritonitis) •May lead to infertility, ectopic pregnancy, sepsis •Signs: pelvic pain incl. chronic, painful intercourse, painful menstruation, vaginal bleeding; in acute stage incl. fever, chills •Prevention of STD • gbp360 PID – chronic inflammation + ovarian torsion – hemorrhagic necrosis Endometriosis •Foci of functional endometrium (glands + stroma) in an ectopic localisation – outside of the uterus; possible retrograde flow + migration, implantation, ?vascular spread, ?inborn •Ovaries, cavum Douglasi, fallopian tubes, peritoneum, bladder, umbilical skin, … lung, bones …) •Estrogen dependent, changes during menstruation cycle •Hemorrhagic (chocolate) cysts, hemosiderin pigmentation, scarring •Pain (dysmenorrhea – painful menstruation, dyspareunia), adhesions, infertility •Possible source of endometrioid adenocarcinoma • Image085 Endometroid cyst Ovarian cystic disease •Non-neoplastic •inclusion cyst: small, from superficial epithelium •functional cyst: stages of ovum maturation/release: follicular, luteal •polycystic ovary syndrome: systemic metabolic/hormonal disorder, obesity, infertility, male type of face/body hair, •endometriosis • •Neoplastic: according to the tissue of origin: surface epithelial tumors, germ cell tu, sex-cord stromal tu, metastatic tu, etc. • Ovarian cystic disease •Signs: according to the size + localization, hormone production •Pain, abdominal pressure •Discomfort during urination, bowel movement, intercourse •Sudden/sharp pain: rupture, torsion •Endometrial changes due to excessive hormone level (mostly estrogen) Follicular cyst • Non-ruptured (no ovulation) enlarging follicle •Prolongated estrogen release without progestins •Endometrial hyperplasia common Ovarian tumors •3rd most common tumors of female genital tract •80% benign, mostly 20-45 years of age •20% malignant, 40-65 years of age, commonly late diagnosis (metastatic disease) → high mortality •Risk factors variable, according to the type of tumor •Familiar genetic factors (+ breast ca), nulliparity → risk of ovarian carcinoma •90% sporadic • gbp5100 Dermoid cyst – mature cystic teratoma: most common female germ cell tumor, benign Ovarian cancer •Signs: abdominal bloating/discomfort, flatulence, local pelvic pain, fatigue •No reliable screening test, marker Ca-125 used •Pelvic ultrasound possible •High risk of recurrence •Lung, liver, lymph node metastasis •Treatment: surgery (→premature menopause), chemotherapy (side effects) Surface epithelial tumors •Biologic potential •Benign •commonly in form of cystadenoma •Low malignant potential •borderline malignancy – moderate atypias, mitotic activity, architectonic changes (multilayering, irregular papillary budding), ! no invasion, but non-invasive peritoneal implants possible •Malignant •carcinoma • ov-tu-max-ma01 Mucinous cystic tumor of low malignant potential Menstruation cycle ut-cyklus-sch03 Early proliferation Late proliferation Early secretion Late secretion Menstruation Disorders of menstruation cycle •Psychogenic – sec. amenorrhea, psychogenic sterility •Hypothalamic •Pituitary – idiopatic, secondary (inflammation, tumors,…) •Gonadal •Uterine •Metabolic – endocrine (thyroid, adrenals), hepatic •Nutritional Abnormal menstruation cycle •Usual clinical presentation – abnormal bleeding •Hormonal dysbalance, variable origin •Non-secretory ← abnormal estrogenic stimulation •↑ E → hyperproliferative → hyperplastic endometrium (anovulatory cycle) • •Secretory ← abnormal progestins •↓ P → hyposecretory endometrium (luteal phase insufficiency) •↑ P exogenous (contraception) - stroma-glandular dissociation – pseudo-decidualized stroma + atrophic glands • •Irregular, mixed ← E+P dysbalance •irregular shedding – mixed secretory + menstrual + proliferative • Endometrial polyp •up to ¼ women during fertile life •common in climacterium •dysfunctional bleeding •possible cause of infertility •possible start/localisation of endometrial ca • Tumors of the uterine body •Endometrial lesions: •Non-physiological non-invasive proliferation of endometrium, benign lesion (reactive) → premalignant condition (monoclonal) •Endometrial carcinoma •Tumors of myometrium: •Smooth muscle tumor: leiomyoma (fibroid) • • • Endometrial carcinoma •Most common malignant tumor of female genital tract •2. cervical ca, 3. ovarian tumors • •type I: perimenopause (55-65 years of age) •Cca 80% • •Risk factors: •unopposed estrogenic stimulation – endo-/exogenous •DM, obesity, early menarche - late menopause •Infertility, nulliparity (childless) •Precursor: atypical endometrial hyperplasia •Better prognosis, lymphatic spread possible Endometrial carcinoma •type 2 – cca 15-20%, not directly connected with permanent estrogenic stimulation, in later postmenopause, high grade, aggressive, worse prognosis •Staging – according to the invasion into the uterine wall, cervix, surrounding structures Endometrial carcinoma •Signs: abnormal bleeding – menometroragia in pre- and perimenopause, metrorrhagia in postmenopause; • uncommonly accidental finding • rarely - generalisation •Gross: exophytic, ulcerated, whitish • Endometrial carcinoma gbp420 Leiomyoma •most common benign female tumor (usual in later reproductive age), 40-70% of females •size: mm - cca 20 cm •symptoms due to localisation/topography (bleeding, pain, infertility, compression of adjacent organs) •in pregnancy ↑ risk of abortion, uterine rupture, possible barrier of normal delivery •uterus myomatosus (multiple leiomyomas) •common regressive changes (edema, fibrosis, hyalinisation, calcification) Leiomyoma Image074 Cervical epithelium Image063 Transformation zone: immature epithelium, risk zone for HPV infection, preneoplastic changes Cervical cancer - precursors •LR (low-risk) HPV (6,11) →→ koilocytic atypia of squamous cells •Cervical dysplasia – intraepithelial neoplasia associated with HR (high-risk) HPV: •HR HPV: • 16, 18, 31, 33, 35 • deregulation of the cell cycle, ↑ proliferation, ↓ or arrested maturation •Other risk factors: smoking, high number of births, multiple sexual partners, young age at 1st intercourse (˂17 years), oral contraceptives (in combination with other risk factors), ↓ immunity, other STD • • Cervical cancer - precursors •2 categories of cervical epithelial lesions, according to the risk of progression and clinical management: •LSIL (low-grade squamous intraepithelial lesion) • = CIN I (cervical intraepithelial neoplasia), exophytic or flat condylomatous lesion •mostly self-limited (viral clearance), productive infection, lower rate of progression •only regular check in young, local excision in older females • •HSIL (high-grade squamous intraepithelial lesion) • = CIN II/III + carcinoma in situ (non-invasive carcinoma) •majority persists or progresses to invasive carcinoma •treatment necessary in any age (very careful observation in pregnancy, CIN II in young females) Invasive cervical squamous cell carcinoma •almost always by HSIL progression •mostly starts in the transformation zone •growth: •local progression •size + depth of the invasive component (bleeding) •direct invasion into adjacent organs (bladder, rectum), fistulae •regional LN metastases •distant metastases via blood (lung, liver, bone marrow) •↑ incidence, but mostly lower stages (if screened), ↓ mortality •Treatment side effects common •Prevention: vaccination (incl. males), most common types are covered by the immunization, crossed immunity possible; further evolution ? – spread of less common types possible Cervical cancer gbp340 Cervical cancer – late stage Image070 Pelvic floor disorders •Lesions of variable pelvic structures: •Organ based / medical treatment (UTI, PID, …) •Common musculoskeletal disorders (lumbar, sacroiliac dysfunction) – treated by most physical therapist •Special musculoskeletal disorders (painful bladder syndrome, pelvic floor muscles dysfunction) - treated by specialist physical therapist • Pelvic floor disorders •Pelvic organ prolapse •Cystocele: bladder prolapse (loss of support), displacement of the bladder, bulging of anterior vaginal wall •Rectocele: rectum prolapse, bulging of posterior vaginal wall •Uterine prolapse: herniation of the uterus into vagina, variable stages, protrusion to the outside possible • • • Pelvic floor disorders •Risk factors: multiple pregnancies, familial risk, aging, history of heavy weight lifting, obesity, chronic constipation, chronic cough •Signs varible, not directly related to the stage •Sense of heaviness/pressure in perineum •Foreign „lump“ in the vagina •Backache, bleeding (irritation) •Cystocele: frequency/urgency, incontinence •Rectocele: incomplete emptying, constipation Pelvic floor disorders •Treatment: •surgery, •mechanical treatment (pessary) •Conservative: pelvic floor muscles rehabilitation/strengthening, biofeedback, stimulation •! Exacerbation of prolapse during other exercises (increased intraabdominal pressure) Breast • Benign breast disorders •Benign epithelial lesions •benign alterations in ducts and lobules •common lesions (benign breast changes) •classification according to the risk of developing subsequent breast carcinoma •Nonproliferative/non-atypical lesions (cyst, fibrosis, usual hyperplasia, …) no risk •palpable irregularities (lumps, granularity), +/-tender •etiology: •hormone dependent •inflammation-associated •diff. dg.: malignant tumors • Benign breast disorders •Symptom + findings •Cyclical swelling, tenderness •Breast pain •Cysts •Nodularity •Nipple discharge •Infections, inflammations Benign breast disorders •Fibroadenoma •Most common breast tumor in young females (peak incidence before 30 years) •Benign, circumscribed, mobile, rubbery •May be painful before menses •Proliferating ducts + increased amount of stroma Breast cancer •Atypical hyperplasia (ductal, lobular)– 5x ↑ risk of invasive cancer • •Carcinoma in situ: intraductal (DCIS) • lobular carcinoma in situ (LCIS) •Monoclonal neoplastic lesions •Direct precursors of invasive cancer •High relative risk of subsequent invasive carcinoma (10x) •Histopathological diagnosis necessary • Breast cancer •commonest malignancy in females in high-income countries • •rising incidence • •falling mortality •screening + better diagnostics •known modifiable risk factors •more effective therapy • •metastases •lymphatic spread – regional LN (mostly axillary) •hematogenous spread (bones, lung, liver, brain…) • Breast cancer •Risk factors: •Age (65+ x younger) •High endogenous estrogen levels, chronic inflammation (incl. obesity) •Early menarche (˂12 years), late menopause (˃55 years) •No full-term pregnancy, no breastfeeding •Late age (˃30 years) at first full term pregnancy •Smoking, alcohol •Radiation exposure •Hormone replacement therapy (long-term) • Breast cancer •Sporadic carcinomas (≈95%) •accidental sequential mutations •mostly perimenopausal/postmenopausal, old age (50-75) • •Familial carcinomas (≈ 5%) •hereditary mutations in some TSG (BRCA1, BRCA2…) •typical in young females (after age of 20) •possible multicentric, bilateral → prophylactic mastectomy •↑ risk of ovarian carcinomas • Breast cancer •Invasive carcinoma of non-specific type (former invasive ductal carcinoma) •Invasive lobular carcinoma •Others • •Screening: mammography, ultrasound •Signs: palpable mass, firm, irregular, painless •New asymmetry, distortion •Nipple discharge •Axillar lympadenopathy Breast cancer •Diagnosis by histopathology •Core-cut biopsy •Excision •Molecular markers important for diagnosis, prognosis, treatment •Combined treatment: •Surgery •Radiation •Hormonal therapy •Biologic therapy •Chemotherapy • • Breast cancer - implications •Possible help with diagnosis •Upper quadrant symptoms of unknown origin •Axillar lymphadenopathy – compression of adjacent structures •Signs of recurrence; local/regional/distant metastasis •Preoperative assessment of general and local functional status •Postoperative rehabilitation, complications and their prevention (lymphedema, decreased range of movements, scarring) •Side effects of chemo-, radiotherapy, hormonal therapy, …