Aims Prostate pathologies Endometriosis Toxemia of Pregnancy Lecture #28 Aims Prostate pathologies Endometriosis Toxemia of Pregnancy Readings; Robbins, Chapters 18 & 19

Prostate Gland Relatively small through childhood Begins to grow at puberty and maintains a constant size from age 20-50. Around age 50 in some men there is a decrease in testosterone and an involution of the prostate gland. Robbins Basic Pathology 18-10

Benign Prostatic Hyperplasia Hyperplasia of prostatic stroma and epithelial cells forming large and discrete nodules. Symptoms Difficulty urinating. Distention of bladder. Due to the compression of the urethra.

Benign Prostatic Hyperplasia Onset Common disorder in men over the age of 50. 20% of men 40 years old. 70% of men 60 years old. 90% of men 70 years old.

Benign Prostatic Hyperplasia Robbins & Cotran’s Pathologic Basis of Disease 21-32

Benign Prostatic Hyperplasia Pathogenesis Dihydrotestosterone (DHT) is a metabolite of testosterone and is the ultimate mediator of prostatic growth. DHT is synthesized in the prostate stroma cells from testosterone. DHT is 10-times more potent in inducing cell division than testosterone. Binds to the receptor longer. Robbins & Cotran’s Pathologic Basis of Disease 21-32

Benign Prostatic Hyperplasia Pathogenesis DHT has an ______________________________ function inducing stromal cell growth. DHT binds to a nuclear receptor and signals the transcription of growth factors that induce cell division. Robbins & Cotran’s Pathologic Basis of Disease 21-32

Benign Prostatic Hyperplasia Pathogenesis DHT had a _______________________________ function inducing epithelial cell growth. DHT binds to a nuclear receptor and signals the transcription of growth factors that induce cell division. Robbins & Cotran’s Pathologic Basis of Disease 21-32

Benign Prostatic Hyperplasia Morphology Not considered a premalignant lesion. Nodules can be diverse Nodules which are primarily glandular are yellow-pink and soft and secrete milky white prostatic fluid. Nodules which are primarily fibromuscular are gray, tough, and non-secretory. Robbins Basic Pathology 18-11 7th Ed.

Benign Prostatic Hyperplasia Histology Nodules may be due to glandular proliferation, glandular dilation, fibrous stroma proliferation (most prevalent), or muscular stroma proliferation. All of these elements are present in each case. Robbins & Cotran’s Pathologic Basis of Disease 23-19B

Benign Prostatic Hyperplasia Treatment Watchful waiting Finasteride (Proscar) Transurethral resection of the prostate gland (400,000/ year in US)

Prostate Cancer Symptoms Early microscopic cancers are usually asymptomatic. Later larger cancers can cause difficulty urinating. Metastasis to the bone can cause back pain.

Prostate Cancer Onset Most common form of cancer in men. Ethnicity is an important factor. Asians rarely have this disease. Caucasian Americans 50-times more likely to have disease than Asians. 2-3% of adult male deaths. Disease of men over the age of 50. Only 1% of cancers are diagnosed before age 50.

Prostate Cancer Factors Age Race Hormone levels (testosterone) Family history Environment.

Prostate Cancer Pathology Cancer cell growth usually stimulated by testosterone. Cancer is spread via direct local invasion (seminal vesicles), blood stream (bone), or lymphatics.

Prostate Cancer Morphology Most common form of ______________________________________. Well defined. Robbins & Cotran’s Pathologic Basis of Disease 21-34 6th Ed.

Prostate Cancer Treatment Early localized disease can be treated by surgery and radiation. Advanced metastatic disease is treated by endocrine therapy (Lupron). Growth can be inhibited by inhibiting the production of testosterone via removal of testes. Additionally, estrogen treatment can inhibit production of testosterone.

Endometriosis Endometriosis is a painful, chronic disease that affects 5 1/2 million women and girls in the USA and Canada, and millions more worldwide. The presence of endometrium in abnormal places including ovaries. This misplaced tissue develops into growths or lesions which respond to the menstrual cycle in the same way that the tissue of the uterine lining does: each month the tissue builds up, breaks down, and sheds.

Endometriosis Symptoms Menstrual irregularities. Pelvic pain. Dysmenorrhea Pelvic pain. Due to internal bleeding, breakdown of the blood and tissues, and inflammation Infertility (30-40%).

Endometriosis Onset Disease of women in active reproductive life (most commonly in their 20-30’s). Effecting ~10% of women.

Endometriosis Morphology Sectioned ovary revealing large endometriotic cyst. Robbins Basic Pathology 19-11

Endometriosis Pathogenesis Regurgitation theory Metaplastic theory Retrograde menstruation through the fallopian tubes. Metaplastic theory Endometrium could arise from originating tissue (coelomic epithelium). ___________________________________ theory Endometrial cells spread via the blood and lymphatics. Robbins Basic Pathology 19-10

Endometriosis Genetics Immune factors Hormone levels Acromase cytochrome P450 in endometriotic tissue can synthesize estrogen. Immune factors Association with allergies.

Endometriosis Treatments Pain mediations Hormonal therapy Surgery Hormonal treatment aims to stop ovulation. Surgery Conservative surgery seeks to remove or destroy the growths. Radical surgery, which may be necessary in severe cases, involves hysterectomy, removal of all growths, and removal of ovaries.

Toxemia of Pregnancy (Preeclampsia and Eclampsia) Symptoms Rapid elevation of blood pressure (hypertension). Weight gain. Large amounts of protein in urine (proteinuria). Excess salt and water retention (edema). Arterial spasm.

Toxemia of Pregnancy (Preeclampsia and Eclampsia) Onset 4-6% of pregnant women in the last few months of pregnancy.

Toxemia of Pregnancy (Preeclampsia and Eclampsia) Pathology Hypotheses: Excess secretion of adrenal or placental hormones. Autoimmune or ___________________________________

Toxemia of Pregnancy (Preeclampsia and Eclampsia) 3 Important Events in Pathogenesis Placental ischemia (Abnormality of placentation leads to ischemia.) Hypertension Due to vasoconstriction Disseminated intravascular coagulation (DIC) unregulated thrombin and plasmin generation → widespread microvascular thrombosis & hemorrhage → ischemia and fibrinolysis → organ damage. Without treatment a high percentage of mothers die.

Toxemia of Pregnancy (Preeclampsia and Eclampsia) Robbins and Cotran’s Pathologic Basis of Disease 22-61

Toxemia of Pregnancy (Preeclampsia and Eclampsia) Treatment Vasodilating drugs Termination of pregnancy Cesarean section.

Next Time Neoplasia Readings; Robbins, Chapter 6

Objectives Understand the symptoms, onset, histology/ morphology, pathogenesis, & treatment of benign prostatic hyperplasia and prostate cancer. Understand the symptoms, onset, histology/ morphology, pathogenesis, & treatment of endometriosis and toxemia of pregnancy.