Class 23 Pt. 2 - Alterations in Reproduction, Neoplasia

Question 1

Fibrocystic Changes (FCC) in the Breast

Answer 1

Benign
Most common non-proliferative type of lesion that occurs in the breast
- Increase in the number or formation fo cysts and fibrous tissue in the brest

Risk factors

• Hormonal changes
• Genetics
• Age
• Number of pregnancies regardless of breast feeding
• Associated with diet (caffeine seems to increase fibrocystic changes)
• Exposure to exogenous hormones

Manifestations

• Tend to correlate with hormonal cycles
• Lumpy, bumpy, tender breasts and sometimes nipple discharges during certain parts of the menstrual cycle

Proliferative changes can occur in the breast, but involve the epithelial cells that line the ducts and stroma of the breast

• Epithelial hyperplasia
• Increases chance of breast cancer

Question 2

Breast Cancer

Answer 2

Incidence

• Most common type of cancer
• 2nd leading cause of cancer deaths in Canadian women
• 2012: 22,700 Canadian women diagnoses, 5,100 deaths, 14 die each day, 1/9 women will develop breast cancer in her lifetime
• 2012: 200 men diagnosed, 55 deaths

Risk factors (women)

• Age
• Obesity
• Physical inactivity
• Alcohol
• Heredity (BRCA1 mutated DNA on chromosome 17 and BRCA2 mutated DNA on chromosome 13)
• Reproductive and hormonal factors: the older the woman is at the time of her first birth of her child, the earlier she went through menarche (her first period) and the later at which she experienced menopause; longer exposure to hormonal menstrual cycle
• Irregular periods, birth control, combined hormone replacement therapy (estrogen and progesterone)

Risk factors (men)

• Age (>60)
• Gynecomastia (increased breast tissue)
• Exposure of radiation of the chest wall
• BRCA2 mutated DNA on chromosome 13

Pathogenesis

• Most (70%) arise from epithelial cells of the mammary ducts
• Doesn’t grow large, but metastasize very quickly
• Estrogen thought to be in part responsible for the alterationsin cells, the dysplasia that eventually occurs
• Majority of the tumours are in the upper, outer quadrant of the breast and spread via the lymphatic chains to the opposite breast, to the bones, to the pelvis, lungs, and liver; also adrenal glands, pituitary, and ovaries

Manifestations

• Painless lump, commonly in the upper, outer quadrant of the breast
• Can also be associated with dimpling of the skin (orange like texture)
• May be asymmetry or elevation of the affected breast
• Nipple may be retracted or have a change in appearance or discharge (clear or bloody)

Diagnosis:

• Prevention: self-examination and mammography
• Definitive: biopsy, taking part of the tumour and seeing i the cells have gone through anaplasia

Treatment:

• Surgery (lumpectomy if it is locatlized tumour or radical mastectomy involving the entire breast, lymph nodes and supportive structures
• Usually radiation and or chemotherapy that follows
• Some have hormonal therapy

Question 3

Inflammatory Breast Cancer

Answer 3

Rare but aggressive cancer that develops rapidly

• 1/6% of breast cancers in US, survival rates lower than other forms
• Breast looks very red and swollen, render feeling
• Usually the lump is absent until the cells invade the lymphatic vessels, and then the redness and swelling appears
• Often confused with breast infection, but the whole breast is involved rather than a quadrant

Question 4

Cervical Dysplasia

Answer 4

1/8 women have some degree of cervical cell dysplasia by the time they are 20

• Accounts for 1.1% of female cancer deaths, 1/150 will develop cervical cancer in her lifetime
• HPV is a necessary precursor to the development
• Relatively easily treated and cured if diagnosed early
• Slow growing type of cancer; normally takes 10-12 years before it changes from dysplasia to neoplasia
• Incidence has decreased by 50% and deaths by 60% since 1977; Pap smears
• Vaccine: Gardasil

Risk Factors

• Intercourse before the age of 16 (cerivx cells are not mature and vulnerable to HPV)
• Multiple sexual partners
• Smoking
• Poor nutrition

Manifestation
- Cervix appears white and shiny as a first sign of cancer development

Diagnosis

• Prevention: pap smear detects changes in the cervical cells
• Definitive: biopsy

Treatment: based on staging and severity of the cancer

Question 5

Polyps

Answer 5

Benign masses of endometrial glands, stroma, and blood vessels

• Often mistaken for adenocarcinoma
• Often located in the fundus of the uterus, or right at he top of uterus
• Most common in women 40-60
• Can cause heavy menstrual flow and bleeding between periods
• Tends to occur around the menopausal stage

Question 6

Endometrial Cancer

Answer 6

“Adenocarcinoma”

• Most common type of gynaecological cancer in women
• Originates from the epithelial cells which form the endometrial gland

Risk factors

• Average age of diagnosis is 60
• More common in Caucasians than African ancestry
• Obesity, consume a high fat diet
• Diabetes
• High socioeconomic status
• Infertile or have had no pregnancies, early menarche or late menopause

Manifestations

• Painless abnormal bleeding or persistant irregular bleeding, especially in obese women
• As it progresses, there can be cramping, pelvic discomfort, and enlarged lymph nodes

Diagnosis

• Biopsy
• Can use ultrasound, blood work, x-rays to see if it has metastasized to other areas

Treatment

• Surgery (endometrial ablation: removes just the lining of the uterus or hysterectomy: complete removal of the uterus
• Radiation and chemotherapy

Question 7

Benign Ovarian Cysts

Answer 7

• Usually an increase in the number of these cysts around puberty and menopause (related to hormonal imbalance)
• Often a symptomatic unless seize causes abdominal enlargement
• Occasionally can secrete estrogens and or androgens; signs and symptoms will show
• Growth is directed in the centre of the ovary is encapsulated and contained within the ovary and will push the normal, healthy tissue to the outer rim.

Question 8

Ovarian Cancer

Answer 8

“Silent Killer”

• Second most common reproductive cancer in women
• Most lethal
• Incidence increases with age and greatest between 65-84
• BRCA1 and BRCA@ mutation
• 90% arises from the epithelial cells on the surface of the ovary

Risk factors

• Age (older)
• Family history
• The length of time a woman’s ovarian cycle has not been suppressed by pregnancy, lactation, or birth control pills.

Manifestations

• Very few until the cancer has metastasized; difficult and almost impossible to treat, otherwise vague
• Nausea, vomiting and some bowel changes
• Might have abnormal vaginal bleeding
• Might have a feeling of pressure in the pelvis and in the legs

Question 9

Benign Prostatic Hyperplasia

Answer 9

Gland increases in size.

• Urethra becomes compressed, can cause obstruction
• Common: 80% of men will have some degree of BPH by the time they reach 80, 25-35% change of needing a prostatectomy by 50 .

Risk factors

• Family history
• Race and ethnicity (higher for African ancestry, lowest for Japanese ancestry)
• Age (older)
• Hormonal imbalances (aging causes imbalance in the testosterone-estrogen ratio) and gonadotropin and growth factors
• Consuming a high fat diet
• Use of tobacco

Pathophysiology

• Starts around 40-45 and grows slowly until death
• Begins in the inner layers, norming nodules (nodule hyperplasia)

Symptoms

• Urinary frequency, hesitancy (hard to start)
• Decreased force in the flow (tends to tribble)
• Overflow incontinence due to urethra obstruction
• Backflow of urine into the ureters (hydroureters and increased UTI’s)

Question 10

Prostatic Cancer

Answer 10

Incidence

• One of the most common types of cancer in men
• # 1 cause of cancer in Canadian and American men, and #3 worldwide (Albertan’s have highest risk in Canada)
• Prognosis of surviving in improving. 85% of cancers are now found in a local or regional states, and for those types of cancers, 5-year survival rate is almost 100%

Risk Factors

• Age #1
• High fat diet (alters the production of hormones)

Pathophysiology: multifactorial

• Genetics and environment
• Multifactorial hypothesis: androgens act as a strong tumour promoter by androgen receptor mediated mechanisms; this enhances the weak but carcinogenic effect of estradiol and enhances the growth of cells and eventually leads to a cancerous tumour
• Tumour will invade and metastasize to the lymph nodes, bones, lungs, and liver

Manfestations

• Often asymptomatic until it is far advanced
• First signs are urinary in nature
• There may be rectal obstruction or bone pain (dependent on the tumour)
• May lead to sexual dysfunction (cancer and treatment)

Question 11

Diagnosis for BPH and Prostatic Cancer

Answer 11

Digital Rectal Exam (DRE)

• Men over 50 and men over 45 with family history should have DRE on a regular basis
• Involves putting a finger into the rectum and palpating for the prostate to see if there are any tumours of if it has increased in size

Transrectal Ultrasound (TRUS)
- Ultrasound probe is put into the rectum and the actual size of the prostate can be determined on ultrasound 

Prostate Specific Antigen (PSA) test

• Blood test
• Measure levels of PSA (the bigger the prostate, the more PSA)
• PSA level changes low, may indicate BPH
• PSA level changes rapidly and increases drastically - malignancy

Others

• MRI
• CT scans

TNM scale used

• Tumour
• Nodes
• Malignancy

Question 12

Treatment for BPH or Prostatic Cancer

Answer 12

Watchful waiting

• Because the growth is slow, they watch and wait and PSA levels are monitored closely
• If there is a large increased in PSA levels, they will likely do some vigorous interventions

Cryotherapy

• Probes put into the prostate gland
• Put insome liquid ice and freeze the tumour and tissue to destroy it
• Done with aid of transrectal ultrasound

Brachytherapy

• Implant little radioactive seeds into the tumour and prostate gland, radiation kills the tumour
• Done with aid of transrectal ultrasound

Chemotherapy, hormonal therapy, and surgery

Transurethral Prostatic Resection (TURP)

• Prostate gland is accessed through the urethra via probe
• Probe is knife-like/scalpel device which will cut away and remove the tumour and glandular tissue inside the prostate

Accessing the prostate through the perineum
- More invasive and associated with more adverse effects

Surgery associated with a number of complications

• Infection
• Blood clots
• Scarring of urethra (TURP; can lead to stenosis (abnormal narrowing))
• Bleeding
• Erectile dysfunction (rare) (cutting some of the nerves in perineal approach)
• Absorption of fluid during the procedure (TURP syndrome) (from trying to prevent blood clots by constant irrigation of the bladder with fluid)
• Permanent incontinence (very rare)