Renal, Genitourinary & Breast Pathology Flashcards
Kidney – Function
Structurally complex - —% of body weight, but filters —% of blood through glomeruli
0.4
25
Excretes nitrogenous waste products of metabolism - cleans the blood – turns — L into urine
1.5
Kidney Function
Regulates (2)
Maintains appropriate —- balance
Endocrine organ – secretes —
body water and electrolytes
acid-base
hormones
Endocrine organ – secretes hormones
Renin –
Erythropoietin –
blood pressure
proliferative effect on bone marrow to make RBCs
Nephron – Functional Unit
Morphologic Components
(3)
Glomeruli
Convoluted tubules
Collecting ducts
Juxtaglomerular cells in wall of afferent arteriole
Sensor for
blood pressure
Macula densa in wall of distal convoluted tubule
Sensor for
sodium
Azotemia – Laboratory Findings
(4)
Elevation of blood urea nitrogen and creatinine levels
Usually related to reduced glomerular filtration rate (GFR)
Associated with many primary renal disorders
May also be associated with extra-renal disorders
skipped
Pre-renal azotemia –
hypoperfusion of the kidneys decreases GFR in the
absence of parenchymal damage
Post-renal azotemia –
urine flow obstructed below the level of the kidney
Uremia – Clinical Findings
(3)
Progression of azotemia to produce clinical manifestations and systemic
biochemical abnormalities
Failure of renal excretory function
Metabolic and endocrine alterations
skipped
Uremia
Secondary involvement of organ systems
(4)
Uremic gastroenteritis
Peripheral neuropathy
Uremic fibrinous pericarditis
Uremic stomatitis
Nephrotic syndrome –
(glomerular syndrome) – heavy proteinuria,
hypoalbuminemia, severe edema, hyperlipidemia and lipiduria
Nephritic syndrome –
(glomerular syndrome) – acute onset of grossly-
visible hematuria, mild-to-moderate proteinuria, azotemia, edema and
hypertension (classic presentation of acute post-streptococcal
glomerulonephritis)
Acute renal failure –
oliguria or anuria with recent onset of azotemia. May
result from glomerular injury or acute tubular necrosis
Chronic renal failure –
prolonged symptoms and signs of uremia – the end
result of all renal disease
Urinary tract infections –
bacteriuria and pyuria –
symptomatic or asymptomatic - kidney (pyelonephritis)
or bladder (cystitis)
Nephrolithiasis –
kidney stones - colic, hematuria
Nephrotic Syndrome
(7)
Glomerular syndrome
A non-specific disorder in which the kidneys are damaged, causing them to leak large
amounts of protein from the blood into the urine.
Heavy proteinuria
Hypoalbuminemia
Severe edema
Hyperlipidemia
Lipiduria
Nephritic Syndrome
(8)
Glomerular syndrome
A non-specific disorder in which the kidneys are damaged, causing them to leak protein and red blood cells from the
blood into the urine.
Acute onset
Grossly-visible hematuria
Mild-to-moderate proteinuria
Azotemia
Edema
Hypertension
Glomerulonephritis -
def
tx
an immune mediated disease of
the renal glomeruli
Treated with steroids
Pyelonephritis -
def
tx
an infection of the kidney (not the
glomerulus) usually caused by bacteria and of
retrograde origin
Treated with antibiotics
Post-Streptococcal Glomerulonephritis
(Postinfectious Glomerulonephtitis)
(2)
Acute onset of nephritic syndrome in 9-14 days following
Streptococcal infection
Type III immune injury (Immune complex-mediated inflammation)
skipped
Pyelonephritis
Pathway of Renal Infection
Hematogenous dissemination –
Ascending infection –
Fecal bacteria from —
Culture and sensitivity –
Pyelonephritis is much more common than —
least common
most common
perineal area
Bactrim
glomerulonephritis
Kidney Stones (Nephrolithiasis)
Urolithiasis
(7)
Common
May cause obstruction
Pain
Ascending infection
Hematuria
Pyuria
Lithotripsy
Kidney Stones (Nephrolithiasis)
Urolithiasis
May be associated with
hypercalcemia (for example,
hyperparathyroidism, metastatic skeletal disease,
multiple myeloma)
Renal Cell Carcinoma
(3)
Arises from renal tubular epithelium
Often silent
May grow into renal vein
Wilm’s Tumor
(Nephroblastoma)
(5)
Children under 5 years
Abdominal mass
Chronic low-grade fever
Histopathology consists of several cell
types, some of which resemble abortive
glomeruli and others that resemble skeletal
muscle
Better than 90% 5-year survival
Urothelial Carcinoma
Arises from the
epithelium (transitional epithelium)
— most common site
Painless —
urinary tract lining
Bladder
hematuria
skipped
Urothelial Carcinoma
from (5)
Cigarette smoking, industrial solvents
(beta-naphthlylamine), chronic cystitis,
schistosomiasis, drugs (cyclophosphamide)
Urothelial Carcinoma
Clinical significance depends on (2)
histologic
grade, differentiation and depth of invasion
Prostate – Three Major Diseases
(3)
Prostatitis
Benign prostatic hyperplasia
Adenocarcinoma of prostate
Prostate-Specific Antigen - PSA
(4)
Protein present in the serum at low levels (nl: < 4 ng/mL)
Increased levels may suggest the presence of prostate cancer
Elevated in prostatitis
Velocity of change significant
Prostate-Specific Antigen - PSA
Physiologic functions
(2)
Liquefy semen, allowing sperm to swim freely
Dissolution of cervical mucous cap
Prostatitis
Acute bacterial disease treated with antibiotics
Nodular (Benign)
Prostatic Hyperplasia - BPH
(6)
Obstruction to flow
Urinary frequency
Ascending infections
Rule-out neoplasia
Pharmacologic treatment
Surgical treatment (TURP)
Adenocarcinoma of Prostate
(5)
70% of men develop prostate cancer by 70-80 years of age
Digital prostate examination
Biopsy – multiple cores
Wide variation in clinical behavior
Gleason grading
Testes
Cryptorchidism –
Seminoma –
Infections – (4)
undescended testes
germ cell tumor (malignant)
tuberculosis, mumps, syphilis, gonorrhea
Cryptorchidism
(5)
Absence of one or both testes in the scrotum
Failure of testis to descend from an abdominal position through the
inguinal canal into the scrotum (“undescended” testes)
Infertility
Increased risk for neoplasia
Orchiopexy
Seminoma
(5)
Most common germ cell tumor of testis
Young adults (15-34 years)
Surgery plus radiation therapy and chemotherapy
One of the most treatable and curable cancers
Over 95% long-term survival in early stages
skipped
Infectious Parotitis
(Mumps)
Complications rare in the young and more common in
older individuals
(8)
Orchitis,
Oophoritis,
Mastitis,
Meningitis,
Thyroiditis,
Pancreatitis
Sterility
Hearing loss
Hypospadias
(3)
Developmental defect of the urethra in the
male
Abnormally placed urethral meatus
Urethral meatus opens on the glans penis most
commonly (first degree hypospadias)
Phimosis
Foreskin cannot be fully retracted from the head of the penis
Priapism
(4)
Erect penis or clitoris does not return to its flaccid state, despite the
absence of both physical and psychological stimulation, within
four hours
Medical emergency
Hematologic diseases
Trauma
skipped
Hematologic diseases
(2)
Sickle cell disease
Leukemia
Uterine Leiomyoma
(4)
Benign smooth muscle neoplasm
“Fibroids”
May cause irregular bleeding (metrorrhagia) or
Painful intercourse (dyspareunia)
skipped
Proliferative Lesions:
Endometrial Hyperplasia and Polyps
(2)
Glandular epithelium
Bleeding
Two Major Diseases of the Endometrium
(2)
Endometriosis
Adenocarcinoma
Endometriosis
(4)
Endometrial tissue outside the uterine cavity
Ectopic endometrial tissue influenced by hormonal
changes
Recurring pelvic pain
Symptoms depend on the site involved and worsen with
the menstrual cycle
Risk Factors for
Endometrial Carcinoma
Age –
Obesity –
Infertility –
most common in the 55 to 65 age group
greater synthesis of estrogen in body fat
women who are nulliparous are at
increased risk of endometrial carcinoma
Cervical
Squamous Cell Carcinoma
(4)
Exfoliative cytologic screening for early detection
(Papanicolau smear)
Squamo-columnar junction
High risk HPV sub-types – 16, 18
Vaccination
Cervical Intraepithelial Neoplasia -
Grades I, II, III
(2)
LSIL (low-grade squamous intraepithelial lesion)
HSIL (high-grade squamous intraepithelial lesion)
Teratoma
(5)
A tumor containing tissues from all three germ layers
Most tumors are derived from one cell layer – ectoderm,
endoderm, mesoderm
Generally arise in gonadal tissues
Most commonly seen in the ovary
“Dermoid cyst” of the ovary – a benign cystic teratoma – may
contain a variety of tissues including hair, teeth, bone, cartillage,
thyroid, etc.
Gonorrhea
(5)
Neisseria gonorrhea
“Mother nature’s birth control”
Pelvic inflammatory disease
Tubal scarring
Ectopic pregnancy
Breast
(5)
Glandular epithelium
Ducts
Lobules
Interstitial tissue
Lymphatics
Gynecomastia
(4)
Enlargement of male breast may occur in response to estrogen
Hyperestrinism in male
Bilateral – rule-out hormonal
Unilateral – rule out tumor
Hyperestrinism in male
(4)
Cirrhosis of liver – inability to metabolize estrogens
Klinefelter syndrome
Estrogen-secreting tumors
Estrogen therapy
Fibroadenoma
(3)
Most common benign neoplasm of breast
Discrete, usually solitary, moveable nodule
Young women (third decade)
Lobules - lobular carcinoma
(2)
Lobular carcinoma-in-situ
Invasive lobular carcinoma
Ducts - ductal carcinoma
(2)
Ductal carcinoma-in-situ
Invasive ductal carcinoma
Pathogenesis of Breast Cancer
(3)
Genetic changes
Hormonal influences
Environmental variables
Risk Factors in Breast Cancer
Well-established risk factors
(6)
Age – uncommon < 30 y
Genetics and family history - p53, BRCA1/2
genes
Menstrual history – early menarche (<12y),
late menopause (>55y)
Length of reproductive life
Nulliparous – having children is protective
Geographic variation
Risk Factors in Breast Cancer
Other risk factors
(3)
Exogenous estrogens – postmenopausal
hormone replacement therapy
Oral contraceptives – newer formulations of
balanced, low doses of estrogen and
progestin safe
Ionizing radiation during breast development
Risk Factors in Breast Cancer
Less well-established risk factors
(4)
Alcohol consumption
High fat diet
Obesity
Cigarette smoking
skipped
Genetic Changes
Familial syndromes
(4)
Li-Fraumeni Syndrome –
Cowden Syndrome –
Ataxia-telangiectasia
gene –
BRCA1/BRCA2 –
Li-Fraumeni Syndrome –
germ-line mutations in p53
Cowden Syndrome –
germ-line mutations in
PTEN
Ataxia-telangiectasia
gene –
DNA repair genes
BRCA1/BRCA2 –
germ-line
mutations
Genetic Changes
HER2/NEU proto-oncogene
(4)
Epidermal growth factor
receptor
Amplified in 30% of breast
cancers
Overexpression
associated with poor
prognosis
Therapeutic intervention –
Herceptin (trastuzumab)
skipped
Genetic Changes con’t
(5)
Amplification of RAS and MYC
(proto-oncogenes)
Mutations of Rb and p53 (tumor
suppressor genes)
Estrogen receptor positivity
Therapeutic intervention -
Tamoxifen
Progesterone receptor
positivity
Hormonal Changes – Risk Factors
Increased exposure to estrogen
(3)
Long duration of reproductive life (More estrogen)
Nulliparity – having children is protective
Late age at birth of first child
skipped
Summary of Exposure to Estrogen
and Breast Cancer Risk
Estrogen exposure has a proliferative effect on breast tissue.
Proliferative breast disease found on biopsy indicates an exposure
to increased levels of estrogen. An increased risk of breast cancer
is found in women who have proliferative breast disease.
The more estrogen the breasts are exposed to over a lifetime, the
higher the risk of breast cancer. During each monthly menstrual
cycle, the breasts are exposed to increased estrogen levels,
especially at the time of ovulation.
Both early age at the start of menstrual cycles (menarche) and
late menopause increase breast cancer risk through increased
exposure to estrogen during more menstrual cycles.
Late age for menarche and early age for menopause decrease
breast cancer risk through fewer menstrual cycles.
Birth control pills and hormone replacement therapy increase
breast cancer risk through increased exposure to estrogen.
Removal of both ovaries before natural menopause decreases
breast cancer risk by decreasing levels of estrogen.
Alcohol consumption. The more alcohol consumed, the more
impaired the liver becomes in its ability to metabolize estrogen.
Therefore, alcohol consumption increases breast cancer.
Obesity. This is because adipose tissue produces small amounts of
estrogen. After menopause, obesity increases breast cancer risk
by increasing the level of estrogen. The more fat, the higher the
estrogen level. Premenopausal obesity does not increase breast
cancer risk. Before menopause, obesity causes hormonal changes
which decrease estrogen production by the ovaries and can even
result in infertility.
Age at birth of first child. There is a change in structure of breast
lobule at pregnancy. Late age at birth of first child increases breast
cancer risk. With late age at birth of first child, type 1 and type 2
breast lobules persist longer. They are more sensitive to
carcinogens. Therefore, risk increases. During the 3rd trimester of
pregnancy (after 32 weeks), the breast lobules mature into Type 3
lobules. Type 4 lobules are formed after childbirth and produce
milk. Both Type 3 and Type 4 lobules are resistant to carcinogens.
Breast Cancer Location
Upper outer quadrant –
Central portion –
Lower outer quadrant –
Upper inner quadrant –
Lower inner quadrant –
50%
20%
10%
10%
10%
Classification of Breast
Cancers (Abridged)
Noninvasive –
(3)
have not penetrated the basement membrane
Ductal carcinoma in situ (DCIS, intraductal carcinoma)
Lobular carcinoma in situ (LCIS)
Classification of Breast
Cancers (Abridged)
Invasive –
(3)
have penetrated the basement membrane (infiltrating)
Invasive ductal carcinoma – most common (scirrhous carcinoma)
Invasive lobular carcinoma
Ductal Carcinoma in Situ
(6)
Precursor lesion to invasive carcinoma
When invasive carcinoma develops in a woman with a previous diagnosis of
DCIS, it is usually in the same breast.
Treatment – surgery and radiation
Tamoxifen –
Aromatase inhibitors –
Good long-term prognosis
Tamoxifen –
antiestrogenic if estrogen receptor + (blocks estrogen receptor)
Aromatase inhibitors –
post-menopausal women (blocks estrogen formation)
Paget’s Disease of Nipple
(4)
Clinical variant of DCIS
Extension of DCIS up to the lactiferous ducts and into
the contiguous skin of the nipple
Crusting exudate over the nipple and areolar skin
Underlying invasive carcinoma in 50%
Lobular Carcinoma in Situ
(4)
One-third of women with LCIS develop invasive
carcinoma
The invasive carcinoma may arise in either breast
LCIS is a marker of increased risk for developing breast
cancer in either breast
Bilateral prophylactic mastectomy may be performed
Invasive Ductal Carcinoma
(4)
Most breast carcinomas (70-80%)
Term used for all carcinomas that cannot be sub-classified into a
specific type (not discussed)
Does not imply that the tumor specifically arises from the duct
system
Carcinoma of “no special type” or “not otherwise specified” (NOS)
are synonyms for invasive ductal carcinoma
skipped
Clinical Features Common to
all Invasive Carcinomas
(3)
Fixation secondary to adherence to pectoral muscles
or deep fascia of chest wall
Adherence to overlying skin with retraction or dimpling
of the skin or nipple
Lymphatic involvement may cause localized
lymphedema with the skin thickened around
exaggerated hair follicles (peau d’orange – orange
peel appearance)
TNM Staging of Breast Cancer
- AJCC
Stage 1 –
metastases
Stage 2 -
Stage 3 –
Stage 4 –
tumor <2 cm, without nodal involvement, no
tumor <5 cm with <3 nodes and no distant
metastases (or more than 5 cm without nodes)
* many categories, any cancer infiltration into skin
and chest wall, with nodes, without disseminated metastases
any cancer with disseminated metastases
skipped
Prognostic Factors
(9)
Size of primary carcinoma
Lymph node involvement and
number of nodes
Distant metastases
Histologic grade
Histologic type
Estrogen or progesterone receptor
expression - Tamoxifen
Proliferative rate
Aneuploidy
HER2/NEU overexpression -
Herceptin
Five Year Survival of
Breast Cancer by Stages DCIS or LCIS - 92%
Stage 1 – –%
Stage 2 – –%
Stage 3 – –%
Stage 4 – –%
For all stages combined, 10 year survival is about –%
Natural history is long with metastases sometimes appearing decades after the initial diagnosis
87
75
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