Fa: Step 2 Ck. Gynecology.

Front 1

Give the length of each phase of the menstrual cycle.

Back 1

follicular phase: days 1-13, but varies
ovulation: day 14 (or first day following follicular phase)
luteal phase: days 15-28 (this is always 14 days, the length of time the corpus luteum can survive without further LH)

Front 2

Describe the hormonal trends (LH, FSH, estrogen, progesterone) of the normal menstrual cycle.

Back 2

Front 3

What is the definition of premature menopause?

Back 3

ovarian failure and menstrual cessation before age 40

Front 4

What are the predominant features of menopause?

Back 4

"HAVOC"

Hot flashes (vasomotor instability)
Atrophy of the
Vagina
Osteoporosis
Coronary artery disease

Front 5

What laboratory changes are observed in menopause?

Back 5

first: increased FSH
next: increased LH

total cholesterol increased, HDL decreased

Front 6

What is the treatment for the vasomotor symptoms of menopause?

Back 6

hormone replacement therapy with combination estrogen and progestin

Front 7

What are the risks associated with hormone replacement therapy (HRT)?

Back 7

increased cardiovascular morbidity and mortality

may increase risk of breast and endometrial cancers

Front 8

Why is progestin included in HRT?

Back 8

unopposed estrogen in patients with a uterus predisposes to endometrial cancer

post-hysterectomy patients do not need progestin

Front 9

What are contraindications to HRT (6)?

Back 9

vaginal bleeding
suspected or known BRCA
endometrial CA
history of thromboembolism
chronic liver disease
hypertriglyceridemia

Front 10

What non-HRT therapy can be offered to menopausal patients to reduce the frequency of hot flashes?

Back 10

venlafaxine
clonidine (less common)

Front 11

What is the treatment for vaginal atrophy of menopause?

Back 11

estrogen vaginal cream (short term)
estradiol vaginal ring (long-term)

Front 12

What percent of sexually active, premenopausal women will become pregnant within one year if no contraception is used?

Back 12

85%

Front 13

What are the absolute contraindications to estrogen-containing methods of contraception?

Back 13

pregnancy
history of CAD or DVT
BRCA
undiagnosd abnormal vaginal bleeding
estrogen-dependent CA
benign or malignant liver neoplasm
current tobacco use + age >35

Front 14

What are the absolute contraindications to use of IUDs?

Back 14

known or suspected pregnancy
unexplained vaginal bleeding
current purulent cervicitis
active or recurrent PID (within 3 mos)
confirmed symptomatic actinomycosis
bicornuate or septate uterus
cervical or uterine CA
Pap smear with SIL or two atypical Pap smears
history of heart valve replacement or artificial joints

Front 15

Give the DDx of pediatric vaginal discharge (5).

Back 15

infectious vulvovaginitis
STD resulting from sexual abuse
foreign objects
candidal infections
sarcoma botryoides (rhabdomyosarcoma)

Front 16

Describe the two types of precocious puberty.

Back 16

central: results from early activation of hypothalamic GnRH production; most commonly idiopathic; may be related to obesity; may be caused by CNS tumors

peripheral: also called pseudo-precocious; results from non-hypothalamic GnRH production

Front 17

Distinguish between signs of estrogen excess and signs of androgen excess in precocious puberty.

Back 17

estrogen excess: breast development and possibly vaginal bleeding

androgen excess: pubic and/or axillary hair, enlarged clitoris, acne, increased body odor

Front 18

What do estrogen excess and androgen excess suggest, respectively?

Back 18

estrogen excess: ovarian cysts or tumors

androgen excess: adrenal tumors or congenital adrenal hyperplasia

Front 19

What is the first step in the diagnosis of precocious puberty?

Back 19

obtain wrist/hand x-ray to assess bone age

if bone age is within 1y of chronological age, puberty has not begun or has just begun

if bone age is >2y from chronological age, puberty has been present for at least one year or is progressing rapidly

Front 20

What is the second step in diagnosis of precocious puberty, after determination of bone age?

Back 20

conduct a GnRH (leuprolide) stimulation test

Front 21

How can central precocious puberty be distinguished from peripheral precocious puberty using the GnRH (leuprolide) stimulation test?

Back 21

central: LH response to GnRH stim test is positive (obtain cranial MRI to look for CNS tumors)

peripheral: LH response to GnRH stim test is negative

Front 22

What steps should be taken if a GnRH (leuprolide) stimulation test for precocious puberty is negative?

Back 22

workup for peripheral precocious puberty:
obtain U/S of ovaries and/or adrenal glands
measure estradiol (increased in ovarian cysts/tumors)
measure androgens
measure 17-OH progesterone

Front 23

What is the treatment for central precocious puberty?

Back 23

leuprolide

with treatment, physical changes regress or cease to progress

Front 24

What is the treatment for peripheral precocious puberty?

Back 24

treat the cause

ovarian cysts: usually no Tx necessary
CAH: treat with corticosteroids; surgery not required for Tx of ambiguous genitalia
adrenal/ovarian tumors: surgical resection
McCune-Albright syndrome: antiestrogen medications (e.g. tamoxifen) and estrogen synthesis blockers (ketoconazole, testolactone)

Front 25

Define primary amenorrhea.

Back 25

absence of menses by age 16 with secondary sexual development present

or

absence of secondary sexual characteristics by age 14

Front 26

Give the possible etiologies of primary amenorrhea with absent secondary sexual characteristics (no estrogen production).

Back 26

constitutional growth delay (MCC)
primary ovarian insufficiency (most commonly Turner's)
central hypogonadism

Front 27

What factors may cause central hypogonadism?

Back 27

undernourishment
stress
prolactinemia
exercise
CNS tumors or cranial irradiation
Kallmann's syndrome (isolated gonadotropin deficiency; associated with anosmia)

Front 28

Give the possible etiologies of primary amenorrhea WITH secondary sexual characteristics (evidence of estrogen production but other genetic or anatomic problems).

Back 28

Mullerian agenesis
imperforate hymen
complete androgen insensitivity (breast development, but no menses or pubic hair)

Front 29

What is the first step in the diagnosis of primary amenorrhea?

Back 29

pregnancy test

Front 30

What is the second step in the diagnosis of primary amenorrhea, after obtaining a pregnancy test?

Back 30

radiograph to determine bone age

Front 31

How should bone age results be interpreted in the workup of primary amenorrhea?

Back 31

if bone age <12 years (short stature) with normal growth velocity, constitutional growth delay is probable cause

if bone age is >12 years but no sign of puberty, obtain LH, FSH and consider location of problem on HPA axis

Front 32

Interpret the following laboratory findings in a patient with primary amenorrhea:

1. low GnRH; low LH, FSH; low estrogen, progesterone (prepuberty levels)
2. low GnRH; low LH, FSH; low estrogen, progesterone
3. high GnRH; high LH, FSH; low estrogen, progesterone
4. high GnRH; high LH, FSH; high estrogen, progesterone
5. normal pubertal hormone levels

Back 32

1. constitutional growth delay
2. hypogonadotropic hypogonadism (hypothalamic or pituitary problem)
3. hypERgonadotropic hypogonadism (points to ovarian failure to produce estrogen)
4. PCOS or problem with estrogen receptors
5. anatomic problem (menstrual blood can't get out)

Front 33

Give the DDx of primary amenorrhea presenting with hypogonadotropic hypogonadism.

Back 33

Kallmann's syndrome
hypothyroidism
hyperprolactinemia
tumor
infection
trauma
chronic disease
anorexia
excess exercise
weight loss stress

Front 34

Give the DDx of primary amenorrhea presenting with hypERgonadotropic hypogonadism.

Back 34

Turner's syndrome
premature ovarian failure (chemo, radiation, idiopathic)
pure gonadal dysgenesis
Savage's syndrome (gonadotropin-resistant ovary)

Front 35

Give the DDx of secondary amenorrhea presenting with hypogonadotropic hypogonadism.

Back 35

Sheehan's syndrome
neoplasms
panhypopituitarism
hyperprolactinemia
hypothyroidism
anorexia
excess exercise
weight loss
stress

Front 36

Give the DDx of secondary amenorrhea presenting with hypERgonadotropic hypogonadism.

Back 36

premature ovarian failure (primary hypogonadism before age 40)
menopause
chemotherapy with alkylating agents

Front 37

Give causes of primary and secondary amenorrhea due to anatomic problems (normal hormone levels).

Back 37

primary:
imperforate hymen
transverse vaginal septum
vaginal and/or cervical agenesis
Mullerian agenesis

secondary:
Asherman's syndrome due to emdometritis, scarring after delivery, or D&C
cervical stenosis

Front 38

Give the treatment for the following causes of primary amenorrhea:

1. constitutional growth delay
2. hypogonadism
3. anatomic

Back 38

1. no treatment needed
2. begin HRT with estrogen alone at lowest dose; after 12-18 mos, begin cyclic estrogen/progesterone therapy
3. generally requires surgical intervention

Front 39

Define secondary amenorrhea.

Back 39

absence of menses for six consecutive months in women who have passed menarche

Front 40

What is the first step in the diagnosis of secondary amenorrhea?

Back 40

pregnancy test

Front 41

What is the second step in the diagnosis of secondary amenorrhea, following a pregnancy test?

Back 41

negative beta-hCG: measure TSH and prolactin to assess for hypothyroidism or hyperprolactinemia

normal beta-hCG: initiate a progestin challenge (10 days of progestin)

Front 42

Describe both positive and negative responses to a progestin challenge.

Back 42

positive progestin challenge (withdrawal bleed): indicates anovulation likely due to non-cyclic gonadotropin secretion, pointing to PCOS or idiopathic anovulation

negative progestin challenge (no bleed): indicates uterine abnormality or estrogen deficiency; check FSH levels

Front 43

What do high and low levels of FSH following a negative progestin challenge indicate, respectively?

Back 43

high FSH: indicates hypERgonadotropic hypogonadism/ovarian failure

low FSH: obtain a cyclic estrogen/progesterone test; a withdrawal bleed from this test indicates hypogonadotropic hypogonadism; no bleeding suggests endometrial or anatomic problem

Front 44

What is the next best step in a woman with secondary amenorrhea and signs of hyperglycemia (polyuria, -dipsia) or hypotension?

Back 44

1mg overnight dexamethasone suppression test to distinguish CAH, Cushing's, Addison's

Front 45

What is the next best step in a woman with secondary amenorrhea and clinical signs of virilization?

Back 45

measure testosterone, DHEAS, and 17-OH progesterone

mild virilization suggests PCOS, CAH, or Cushing's
moderate-severe virilization suggests ovarian or adrenal tumor

Front 46

Give the treatment for secondary amenorrhea of the following etiologies:

1. hypothalamic
2. tumors
3. premature ovarian failure

Back 46

1. reverse underlying cause; induce ovulation with gonadotropins
2. excision; medical therapy for prolactinomas (e.g. bromocriptine, cabergoline)
3. if uterus is present, treat with estrogen plus progestin replacement therapy

Front 47

Define primary dysmenorrhea.

What is the usual mechanism of primary dysmenorrhea?

Back 47

menstrual pain associated with ovulatory cycles in the absence of pathologic findings

uterine vasoconstriction leads to anoxia and sustained contractions mediated by an excess of prostaglandin (PGF2-alpha)

Front 48

What is the treatment for primary dysmenorrhea?

Back 48

NSAIDs
topical heat therapy
combined OCPs
Mirena IUD

Front 49

What is the definition of secondary dysmenorrhea?

Name some common causes of secondary dysmenorrhea (6)

Back 49

menstrual pain for which an organic cause exists

endometriosis, adenomyosis
tumors
fibroids
adhesions
polyps
PID

Front 50

What is the first step in the diagnosis of secondary dysmenorrhea?

Back 50

obtain beta-hCG to exclude ectopic pregnancy

Front 51

What is the second step in the diagnosis of secondary dysmenorrhea, following a negative pregnancy test?

Back 51

CBC w/ diff
UA (r/o UTI)
GC/CT swab (r/o STDs, PID)
stool guaiac (r/o GI pathology)

Front 52

What is the third step in diagnosis of secondary dysmenorrhea after pregnancy test and labs have been negative/normal?

Back 52

look for pelvic pathology causing pain

Front 53

Discuss endometriosis v. adenomyosis with respect to the following characteristic:

location

Back 53

endometriosis: endometrial glands and stroma outside the uterus

adenomyosis: endometrial tissue within the myometrium of uterus

Front 54

Discuss endometriosis v. adenomyosis with respect to the following characteristic:

history, physical exam

Back 54

endometriosis: classically, cyclic pelvic and/or rectal pain with dyspareunia

adenomyosis: noncyclical pain, menorrhagia, enlarged uterus

Front 55

Discuss endometriosis v. adenomyosis with respect to the following characteristic:

diagnosis

Back 55

endometriosis: direct visualization by laparoscopy (blue-black "raspberry" or dark brown "powder burned" appearance; "chocolate cysts" on ovaries)

adenomyosis: ultrasound or MRI

Front 56

Discuss endometriosis v. adenomyosis with respect to the following characteristic:

treatment

Back 56

endometriosis: pharmacologic with combination OCPs or GnRH analogs + danazol; conservative surgical management w/ excision of abnormal tissue; TAH/BSO +/- LoA

adenomyosis: NSAIDs for symptom relief, plus OCPs or progestins; endometrial ablation or resection w/ hysteroscopy; hysterectomy (definitive Tx)

Front 57

Discuss endometriosis v. adenomyosis with respect to the following characteristic:

complications

Back 57

endometriosis: infertility (MCC among menstruating women >30 years)

adenomyosis: endometrial carcinoma (rare)

Front 58

What is the provisional diagnosis for a woman with vaginal bleeding for six or more months following cessation of menstrual function?

Back 58

cancer, until proven otherwise

Front 59

Define the following terms:

1. menorrhagia
2. oligomenorrhea
3. polymenorrhea
4. metrorrhagia
5. menometrorrhagia

Back 59

1. incr. amount of flow (>80 mL blood loss per cycle) or prolonged bleeding (flow lasting >8 days); may lead to anemia
2. incr. length of time between menses (35-90 days)
3. frequent menstruation (<21-day cycle); anovular
4. bleeding between periods
5. excessive and irregular bleeding

Front 60

What are indications for endometrial biopsy?

Back 60

>4mm endometrium in a postmenopausal woman
patient >35 years
obese patient (BMI >35)
diabetic patient

Front 61

What is the management of uterine hemorrhage?

Back 61

high-dose IV estrogen (stabilizes endometrial lining and stops bleeding within 1h)

if bleeding not controlled within 12-24 hours, D&C is indicated

Front 62

What is the management of ovulatory bleeding?

Back 62

NSAIDs to decrease blood loss
if patient is hemodynamically stable, treat with OCPs or a Mirena IUD to thicken endometrium and control bleeding

if not effective within 24h, look for alternative diagnosis

Front 63

What is the general strategy for treating anovulatory bleeding?

Back 63

convert proliferative endometrium to secretory endometrium

Front 64

What is the management of anovulatory bleeding?

Back 64

progestins x10 days to stimulate withdrawal bleeding

if young patient with suspected bleeding disorder, desmopressin followed by rapid incr. in vWF and factor VIII (lasts ~6h)

Front 65

What treatment options are available to stop uterine bleeding if medical management fails?

Back 65

D&C
hysteroscopy (ID polyps, aid in performance of directed uterine biopsies)
hysterectomy or endometrial ablation

Front 66

Define congenital adrenal hyperplasia (CAH).

Back 66

21-hydroxylase deficiency that can present in its most severe, classic form as newborn female infant with ambiguous genitalia and life-threatening salt wasting; milder forms present later in life

11-beta-hydroxylase deficiency is a less common cause of adrenal hyperplasia

Front 67

What is the usual presentation of CAH (5)?

Back 67

excessive hirsutism
acne
amenorrhea and/or abnormal uterine bleeding
infertility
palpable pelvic mass (rare)

Front 68

How is CAH diagnosed?

Back 68

incr. androgens = testosterone >2ng; DHEAS >7mcg/mL (r/o adrenal or ovarian neoplasm
incr. serum testosterone alone, suspect ovarian tumor
incr. DHEAS alone, suspect adrenal source e.g. tumor, Cushing's, CAH
incr. 17-OH progesterone (either basally or in response to ACTH)

Front 69

What is the prevalence and alternative name for PCOS?

Back 69

6-10% among US women of childbearing age

Stein-Leventhal syndrome

Front 70

What criteria must be met for diagnosis of PCOS?

Back 70

Must have two of the following three:

1. polycystic ovaries
2. oligo-/anovulation
3. clinical or biochemical evidence of hyperandrogenism

Front 71

What are the typical findings on history and physical in a patient with PCOS (3)?

Back 71

1. high BP
2. BMI >30
3. stigmata of hyperandrogenism or insulin resistance:
menstrual cycle disturbances
hirsutism
acne
androgenic alopecia
acanthosis nigricans

Front 72

What is the most severe form of PCOS?

Back 72

HAIR-AN syndrome:

HyperAndrogenism
Insulin Resistance
Acanthosis Nigricans

Front 73

How is the diagnosis of PCOS made?

Back 73

laboratory findings of incr. testosterone, DHEAS, DHEA

exclude other causes of hyperandrogenism (check TSH, prolactin, 17-OH progesterone)

evaluate for metabolic abnormalities with 2h glucose tolerance test, fasting lipid panel

Front 74

What is the "pearl necklace" sign?

How common is it?

Back 74

>8 small, subcapsular ovarian follicles seen on ultrasound

found in 2/3rds of women with PCOS

Front 75

What is the ratio of LH:FSH in PCOS?

Back 75

LH:FSH will be >2:1

Front 76

Give the treatment of PCOS for the following:

1. women who are not attempting to conceive
2. women who ARE attempting to conceive

Back 76

1. combination of OCPs, progestin, metformin (or other insulin-sensitizing agents)
2. clomiphene +/- metformin (first-line treatment for ovulatory stimulation)

Front 77

Give the treatment for the following symptoms of PCOS:

1. hirsutism
2. CV risk factors/lipid levels

Back 77

1. combination OCPs (first-line); antiandrogens (spironolactone, finasteride) and metformin (second-line)
2. diet, weight loss, exercise +/- statin

Front 78

What are the complications of PCOS?

Back 78

incr. risk of early-onset type 2 DM
incr. risk of miscarriages
incr. long-term risk of breast, endometrial cancers due to unopposed estrogen secretion

Front 79

What is the definition of infertility?

Back 79

inability to conceive after 12 months of normal, regular, unprotected sexual activity

Front 80

What %of infertile couples are due to male causes; what % due to female causes?

Back 80

male causes: 25%
female causes: 58%
unexplained: 17%

Front 81

What are the four major causes of male infertility?

Back 81

In order of descending frequency:

unknown
primary hypogonadism (high FSH)
disordered sperm transport
secondary hypogonadism (low LH and FSH)

Front 82

What are the four major causes of female infertility?

Back 82

In order of descending frequency:

hypothalamic/pituitary causes
PCOS
premature ovarian failure
uterine or outflow tract disorders

Front 83

What is the presentation of vaginitis?

Back 83

change in discharge
malodor
pruritus
irritation
burning
swelling
dyspareunia
dysuria

Front 84

Name two normal vaginal secretions.

Back 84

midcycle estrogen surge: clear, elastic, mucoid secretions

luteal phase/pregnancy: thick and white secretions; adherent to vaginal wall

Front 85

What are common causes of acute pelvic pain?

Back 85

"A ROPE"

Appendicitis
Rupture ovarian cyst
Ovarian torsion/abscess
PID
Ectopic prenancy

Front 86

What are the available outpatient regimens for treatment of PID?

Back 86

1. ofloxacin/levofloxacin x14d +/- metronidazole x14d

2. ceftriaxone IM x1 dose

3. cefoxitin + probenecid + doxycycline x14d +/- metronidazole x14d

Front 87

What are the available inpatient regimens for treatment of PID?

Back 87

1. cefoxitin/cefotetan + doxycycline x14d

2. clindamycin + gentamicin x14d

Front 88

What is the risk of infertility following successive eipsodes of PID?

Back 88

1st episode: 10%
2nd episode: 25%
3rd episode: 50%

Front 89

What is the causative agent of toxic shock syndrome?

What are the presenting symptoms?

Back 89

pre-formed S. aureus toxin (TSST-1)

abrupt onset of fever, vomiting, watery diarrhea
diffuse macular erythematous rash
nonpurulent conjunctivitis
desquamation, especially of palms and soles

Front 90

What is the treatment of toxic shock syndrome?

Back 90

rapid rehydration
antistaphylococcal drugs (nafcillin, oxacillin; vancomycin if penicillin allergy)
corticosteroids to decrease symptoms, fever
manage renal or cardiac failure

Front 91

What is the mortality rate associated with toxic shock syndrome?

What are the three major causes of death?

Back 91

3-6%

ARDS
intractable hypotension
hemorrhage secondary to DIC

Front 92

What is the most common benign neoplasm of the female genital tract?

What is the rate of malignant transformation of these neoplasms?

Back 92

uterine leiomyoma (fibroids)

0.1-0.5%

Front 93

What is the pharmacologic treatment of uterine fibroids?

Back 93

NSAIDs
combined OCPs
medroxyprogesterone/danazol (slow or stop bleeding)
GnRH analogs (decr. size of myomas, suppress further growth, decr. surrounding vascularity)

Front 94

What is the surgical treatment of uterine fibroids?

When is emergent surgery indicated?

Back 94

myomectomy or hysteroscopy with leiomyoma resection
hysterectomy for women who have completed childbearing
uterine artery embolization (~25% will need further invasive Tx)


for torsion of pendunculated myoma

Front 95

What health risks are associated with exposure to diethylstilbestrol (DES)?

Back 95

for woman who took DES:
incr. risk of BRCA (~30% over general population)

female offspring of women treated with DES:
incr. risk of clear cell adenocarcinoma of vagina and cervix
incr. risk of genital tract structural anomalies
incr. risk of fertility problems

Front 96

What is the five-year overall survival for women with carcinoma of the cervix?

Back 96

68% in Caucasians
55% in African-Americans

Front 97

Where does vaginal cancer typically present?

Back 97

upper 1/3rd of vagina (75% of patients)

Front 98

Give the tumor marker for the following types of ovarian tumors:

1. epithelial
2. endodermal sinus
3. embryonal carcinoma
4. choriocarcinoma
5. dysgerminoma
6. granulosa cell

Back 98

1. CA-125
2. AFP
3. AFP, hCG
4. hCG
5. LDH
6. inhibin

Front 99

What are causes of female urinary incontinence without specific urogenital pathology?

Back 99

"DIAPPERS"

Delirium/confusional state
Infection
Atrophic urethritis/vaginitis
Pharmaceutical
Psychiatric causes (esp. depression)
Excessive urinary output (hyperglycemia, hypercalcemia, CHF)
Restricted mobility
Stool impaction

Front 100

Describe the following types of female urinary incontinence:

1. total
2. stress
3. urge
4. overflow

Back 100

1. uncontrolled loss at all times, in all positions
2. after incr. intra-abdominal pressure e.g. sneezing, lifting
3. strong, unexpected urge to void that is unrelated to position or activity
4. chronic urinary retention

Front 101

Give the treatment for the following types of female urinary incontinence:

1. total
2. stress
3. urge
4. overflow

Back 101

1. surgery
2. Kegel exercises and pessary; vaginal vault suspension surgery
3. anticholinergic medications or TCAs; biofeedback training
4. placement of urethral catheter in acute settings; timed voiding; treat underlying disease

Front 102

What is the role of fine-needle aspiration in the evaluation of breast masses?

Back 102

if cyst: alleviates pain and confirms cystic nature

diagnosis of fibroadenoma

Front 103

Fibrocystic change v. fibroadenoma: which changes in size during menstrual cycle?

Back 103

fibrocystic change

as name implies, this is a condition that involves exaggerated stromal tissue response (change) to hormones and growth factors

Front 104

What % of breast cancers occur in the upper outer margin of the breast, including the axillary "tail?"

Back 104

60%

Front 105

What is the first step in evaluation of a suspicious breast mass?

Back 105

depends on woman's age:

mammography in postmenopausal women or those older than 30

ultrasound in women younger than 30

Front 106

What are tumor markers for recurrent BRCA?

Back 106

CEA
CA15-3
CA27-29

Front 107

What laboratory values suggest metastatic breast cancer?

Back 107

incr. ESR
incr. alk phos (indicates liver/bone mets)
incr. Ca2+

Front 108

What is the pharmacologic treatment of breast cancer?

Back 108

all hormone receptor positive patients should receive tamoxifen
ER negative patients should receive chemotherapy
trastuzumab for HER2/neu-expressing cancers

Front 109

What are contraindications to breast-conserving surgical treatment?

Back 109

large tumor size
subareolar location
multifocal tumors
fixation to chest wall
involvement of nipple or overlying skin

Front 110

Give the staging criteria for breast cancer.

Back 110

Stage I: tumor size <2cm
Stage II: tumor size 2-5 cm
Stage III: axillary node involvement
Stage IV: distant metastasis