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Chapter 5 • Amenorrhea
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59
DIFFERENTIAL DIAGNOSIS OF
Common Causes of Amenorrhea
CONDITION HISTORY PHYSICAL FINDINGS DIAGNOSTIC STUDIES
PREGNANCY
Pregnancy
CONSTITUTIONAL PROBLEMS
Delayed puberty No menstruation beyond
Anorexia nervosa/
bulimia
Exercise-induced
amenorrhea
Breast tenderness, morning
sickness, urinary frequency
age 16; more than 5 yr
between initiation of breast
growth and menarche
Mean age 13-14; fear of
being fat; low self-esteem;
depression; isolation; overachiever; food is parental
battleground; preoccupation; hair loss; abdominal
bloating, pain, constipation
Began athletic training at
young age; more common
with long distance runners,
ballerinas, gymnasts
Globular, enlarged uterus;
soft, bluish color cervix
Breast stage 1 persists
beyond age 13.4;
PH stage 1 persists
beyond age 14.1
Amenorrhea before or after
weight loss; cachexia;
low body fat; short
stature; yellow, dry,
cold skin; acrocyanosis:
increased lanugo hair;
hypotension, systolic
murmurs, often mitral
valve prolapse
BMI ,17% body fat
b-hCG pregnancy test
positive; ultrasonography
positive
Prolactin normal; TSH,
T4 normal; CBC, U/A
normal; chemistry
profile normal; bone age
normal; skull radiograph
normal
TSH normal; prolactin
normal; FSH and LH
usually low; glucose
normal; ECG: bradycardia, low-voltage changes,
T wave inversions, and
occasional ST segment
depression
TSH normal; prolactin
normal
CONGENITAL OR CHRONIC DISORDERS
Turner syndrome Congenital; short stature; in-
fantile sexual development
Cushing syndrome Weight gain; weakness; back
pain
Thyroid dysfunction Hypothyroid: delayed growth,
weight gain, fatigue,
constipation, cold
intolerance; hyper-thyroid:
weight loss, nervousness,
Polycystic ovary syn-
drome
UTERINE AND OUTFLOW TRACT PROBLEMS
Imperforate hymen/
stenotic cervical os
Asherman syndrome History of uterine infection;
heat intolerance
Infertility Hirsutism; obesity; enlarged
Monthly bloating, cramping,
and pelvic pressure; no
menses; cryotherapy or
other procedure to cervix
tuberculosis, schistosomiasis;
uterine iatrogenic scarring;
curettage, irradiation
Characteristics: webbed
neck, low-set ears,
shield-like chest, short
fourth metacarpal
Moon face, acne, hirsutism,
purple striae of abdomen
Hypothyroid: dry skin,
fine hair, galactorrhea;
hyperthyroid: moist skin,
hyperpigmentation over
bones, thin hair, goiter
ovaries
Fibrotic hymen without
patent opening; stenotic
cervical os
Pelvic examination normal PCT negat ive; E/PCT
Karyotype (45,X)
Cortisol increased;
17-ketosteroids
increased; CT adenoma
Hypothyroid: TSH high;
hyperthyroid: TSH low;
T3 high; T4 high
LH/FSH ratio higher than
3:1; DHEA-S may be
elevated
Clinical diagnosis by history
and findings
negative; hystero scopy
adhesions
Continued
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Chapter 5 • Amenorrhea
DIFFERENTIAL DIAGNOSIS OF
Common Causes of Amenorrhea—cont’d
CONDITION HISTORY PHYSICAL FINDINGS DIAGNOSTIC STUDIES
HYPOTHALAMIC-PITUITARY-OVARIAN AXIS PROBLEM
Ovarian failure Hot flashes, night sweats,
Sheehan syndrome Recent history of postpartum
Medications/chest
wall or nipple
stimulation
Pituitary adenoma Delayed puberty; history of
BMI, Body mass index; CBC, complete blood cell count; CT, computed tomography; DHEA-S, dehydroepiandrosterone sulfate; ECG, electrocardiogram; E/PCT, estrogen/progesterone challenge test; FSH, follicle-stimulating hormone; LH, luteinizing hormone; MRI, magnetic resonance imaging;
PCT, progesterone challenge test; PH, pubic hair; RBCs, red blood cells; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; U/A,
urinalysis.
insomnia, mood changes
hemorrhage and shock
during delivery
Breast nipple discharge;
history of dopamine
antagonists, estrogens, or
illicit drugs; stimulation to
nipples: exercise or sexual;
history of chest wall
surgery or herpes zoster
visual changes, increasing
headaches
References and Readings
Bielak KS, Harris S: Amenorrhea, e-Medicine, 2010. Retrieved from
http://emedicinemedscape.com/article/953850-overview.
Deligeoroglou E, Athanasopoulos N, Tsimaris P, et al: Evaluation
and management of adolescent amenorrhea, Ann NY Acad Sci
1205:10, 2010.
Deligeoroglou E, Tsimaris P: Menstrual disturbances in puberty,
Best Pract Res Clin Obstet Gynaecol 24:157, 2010.
Goswami D, Conway GS: Premature ovarian failure, Hum Reprod
Update 11:391, 2005.
Gray S: Menstrual disorders, Pediatrics Rev 34:1, 2013.
Heiman D: Amenorrhea, Prim Care 36:1, 2009.
Pale, dry vaginal
mucosa; few rugae
Hair loss; depigmentation
of skin; mammary and
genital atrophy
Nipple discharge: bilateral;
multiduct; milky, clear,
or yellowish discharge
Visual field defects;
galactorrhea
Javed A, Tebben PJ, Fischer PR, Lteif AN: Female athlete triad and
its components: Toward improved screening and management,
Mayo Clinic Proc 88:996–1009, 2013. Retrieved from www.
sciencedirect.com/science/article/pii/S0025619613005545.
Klein DA, Poth MA: Amenorrhea: An approach to diagnosis and
management, Am Fam Physician 87:781, 2013.
Practice Committee of American Society for Reproductive Medicine.
Current evaluation of amenorrhea, Fertil Steril 90:S219–225, 2008.
Welt CK, Carmina E: Lifecycle of polycystic ovary syndrome
(PCOS): From in utero to menopause, J Clin Endocrinol Metab
98:4629, 2013.
Wilson GR, Haddad JE, Haddad CJ: Amenorrhea: Common causes
and evaluation, Compr Ther 31:270, 2005.
FSH and LH high;
estradiol low
Pituitary and end-organ
hormones low;
hemoglobin low
Wet mount or hemoccult
of nipple discharge:
negative for RBCs;
prolactin high; conedown view of sella
turcica; MRI or CT
with contrast
Prolactin high; cone-down
view of sella turcica
positive; MRI or CT with
contrast positive
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Breast Lumps and Nipple
6
p to 90% of all breast lumps are found by the
U
woman or her partner before diagnosis using
clinical breast examination (CBE) or mammography. The three most common breast lumps are broadenomas, brocystic breast changes, and breast
carcinoma. Fibroadenomas are benign solid tumors
most frequently seen in women younger than age 30.
Fibrocystic breast changes are a heterogeneous
group of nonproliferative changes of stromal and/or
glandular elements of the breast tissue that includes
benign cysts, diffuse and localized nodularity, nipple
discharge, and breast tenderness. Fibrocystic symptoms are seen with great frequency in women age
30 to 50 years, but less often in those who are
menopausal.
Breast carcinoma is the most common cancer in
women and the second leading cause of cancerrelated death. The risk of breast cancer in women
rises steadily with age and accelerates rapidly after
the age of 50. Although benign conditions that affect
the breast are more common, the presence of a lump
raises legitimate fears. The goal of the assessment
process is to reach a diagnosis that addresses the
possibility of breast cancer.
Nipple discharge is a common complaint among
postmenarchal female clients. It is often related to
pregnancy, recent breastfeeding, or estrogenic medications. In women who are not lactating, nipple
discharge is most frequently caused by intraductal
papilloma, duct ectasia, or cancer. Nipple discharge
is more commonly caused by benign lesions than by
cancerous ones. Physiological stimulation (e.g.,
sucking, pregnancy, mechanical stimulation) of the
breasts can produce discharge, as can breast trauma
and inflammation (e.g., herpes zoster, mammoplasty), pituitary disorders (e.g., irradiation of pituitary), or tranquilizing drugs (e.g., phenothiazines,
methyldopa).
Discharge
DIAGNOSTIC REASONING: FOCUSED
HISTORY FOR BREAST LUMPS
Is this lump likely to be malignant?
Key Questions
l
How long has the lump been present?
l
Is the lump changing (e.g., getting bigger, worse, or
more painful)?
l
Is the lump in one breast only, or are there lumps in
both breasts?
l
When was your last menstrual period?
l
Is there any discharge from the nipple? If so, describe it.
l
Have you recently been treated for a breast infection?
Duration and Growth
The primary presenting complaint of a malignant lesion
is that of a single, hard, painless lump in the breast that
is unchanged by the cyclic hormonal milieu. A change
from the patient’s normal physical ndings is the
most persuasive criterion for considering a diagnosis
of breast cancer.
Malignant lumps are more likely to be new lumps
that show progressive increase in size. The lump
grows until there is an alteration in the contour of the
breast tissue. An unchanged lump of long duration
(years) is almost always benign. Half of all newly
appearing benign cysts resolve within two or three
menstrual cycles.
Unilateral versus Bilateral
Breast lumps found bilaterally in identical quadrants of
the breast are more likely to be benign. A solitary unilateral lump, although usually a cyst, broadenoma, or
lipoma (rare), raises more suspicion for malignancy.
Postmenopausal
Cyclic cysts of the breast are less common after
menopause and necessitate diagnostic investigation.
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Chapter 6 • Breast Lumps and Nipple Discharge
A postmenopausal woman with unilateral mastalgia
(breast pain) has a greater risk for breast cancer. Perimenopausal and postmenopausal women are also at
greater statistical risk for breast cancer because of the
higher incidence of breast cancer as they age. A new
breast lump in a postmenopausal woman warrants a
high degree of suspicion for cancer.
Nipple Discharge With a Lump
The occurrence of nipple discharge, with the presence of
a lump, is worrisome because it can represent a ductal
cancer. This condition demands further investigation
such as mammogram, ductogram, or biopsy.
Infection
Any residual masses in the breast after antibiotic therapy
are suspicious for malignancy and require biopsy.
Does the person have additional risk factors for breast
cancer?
Key Questions
l
Have you ever had breast cancer or ductal cancer in
situ?
l
Have you ever had a breast biopsy that showed
atypical cells?
l
Do you have a family history of breast cancer (i.e.,
rst-degree relative)?
l
Have you ever had ovarian, endometrial, colon, or
thyroid cancer?
l
Do you have a family history of ovarian, endome-
trial, colon, or prostate cancer?
l
Have you ever received radiation to the chest, or had
a malignancy in childhood?
Risk Factors
The presence of risk factors in a woman who has a
lump, raises the index of suspicion for malignancy. It
is important to remember that the absence of such risk
factors is not cancer protective. About 70% to 80% of
all women with breast cancer have no risk factors for
malignancy. Women with a personal history of breast
cancer, ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia
(ALH), or lobular carcinoma in situ (LCIS) are usually
evaluated every 6 months by a breast specialist, because of their increased risk for malignancy. Malignant
breast tumors in adolescents are more likely to be a
metastasis than a primary tumor such as Hodgkin lymphoma, rhabdomyosarcoma, or neuroblastoma.
A history of chest wall irradiation is a risk factor. See
Box 6-1 for a summary of characteristics that could
increase a woman’s risk for breast cancer.
Is this condition more likely to be benign?
Key Questions
l
How old are you?
l
Do you have a history of cystic breast changes or
lumpy breasts?
l
Does this lump feel like other lumps you have had?
l
Do the lumps change with your periods?
l
Have you ever had a mammogram or ultrasound?
Why was it done? What were the results?
l
Have you ever had a lump drained or biopsied? What
was the diagnosis?
l
Do you have breast implants?
Age
Fibrocystic breast changes occur predominantly between the ages of 20 and 30. Fibroadenomas are more
frequent in women age 15 to 39. Intraductal papilloma
Box 6-1
Primary Risk Factors
for Breast Cancer
FEMALE GENDER
AGE
75% of all cases occur after age 50; no plateau effect with
age.
PERSONAL HISTORY OF BREAST CANCER OR CANCER IN SITU
DCIS is a precursor of cancer and increases the risk for
invasive breast cancer, usually in the same breast
PREVIOUS HISTORY OF BREAST BIOPSIES FOR NONMALIGNANT
BREAST DISEASE
Biopsy-proved proliferative changes or atypical epithelial
hyperplasia; fibrocystic histological findings that indicate
increased risk of breast cancer are moderate or severe hyperplasia (1.5 to 2 times the risk), atypical hyperplasia
(5 times the risk), and LCIS (8 to 10 times the risk); LCIS
is a marker for cancer rather than a precursor; the cancer
may occur in either breast.
LABORATORY EVIDENCE OF SPECIFIC GENETIC MUTATION
Presence of breast cancer mutation genes BRCA1 or
BRCA2.
PERSONAL HISTORY OF CANCER
Ovarian, endometrial, colon, or thyroid cancers.
FAMILY HISTORY OF BREAST CANCER
In first-degree relatives (mother, sister, or daughter) or in two
or more close relatives.
Chapter 6 • Breast Lumps and Nipple Discharge
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63
and ductal ectasia occur in the age range of 35 to
55 years, whereas breast carcinoma is most prevalent
in women age 40 to 70 years. Any woman older than
25 years who has a breast lump should be evaluated by
CBE, diagnostic mammography, and/or ultrasound.
Magnetic resonance imaging (MRI) sometimes can be
used in addition to mammography and ultrasound. Additional evaluation with tissue biopsy may be required.
Timing, Consistency, and Duration
The most frequent breast complaint is that of a painful,
mobile lump that increases in size and tenderness as
the menstrual cycle approaches. The lump commonly
has discrete borders that allow for measurement of the
length, width, and depth of the lesion by the patient
(e.g., size of a pea). The lump remains prominent on
breast self-examination, is almost always painful to
palpate, and frequently causes pain with changes in
position of the arm on the affected side. Fibrocystic
breast changes exist on a continuum that corresponds
with the menstrual cycle. Tenderness and size variations occur throughout the month.
Previous Mammograms or Biopsies
History or documentation of cyclic changes in lumps
or the presence of glandular breast tissue on a mammogram or ultrasound supports a clinical diagnosis of
benign disease. More convincing evidence of benign
disease occurs when there is a clear uid aspirate from
the cyst, with no residual or recurring breast lump,
with the caveat that benign disease and malignant disease can occur simultaneously.
Breast Implants
With a ruptured implant, augmented breast tissue is
pushed away from the chest wall by the implant.
in a lactating woman is usually associated with mastitis, an inammation of breast tissue, and a blocked
duct. It occurs most often in primiparous nursing mothers, and is usually caused by coagulase-positive Staph-
ylococcus aureus. It can also occur during periods of
weaning, when the ow of milk is disrupted. Inammatory breast cancer in lactating women is rare, but
must be considered.
Sore, Cracked, or Pierced Nipples
Cracked or pierced nipples can be a site for the introduction of infection.
Painful or Hot Breast
Mastitis is characterized by a breast that is painful, hot,
and red. In lactating women, the most frequent symptom is a painful, erythematous lobule in an outer quadrant of the breast. Although mastitis is most common in
lactating women, it can also occur in nonlactating
women, usually as the result of a generalized dermatitis
occurring from insect bites, sunburn, or allergic reactions. However, the most common cause of an inamed
breast in nonlactating women is inammatory breast
cancer. In inammatory breast cancer the entire breast
is swollen, heavy, and edematous.
Fever
Fever is a sign of infectious mastitis and occurs most
often in association with lactation and breastfeeding.
High fever does not occur because of simple breast
engorgement in the postpartum period. Fever does not
usually occur in inammatory breast cancer and is rare
in dermatitis reactions.
DIAGNOSTIC REASONING: FOCUSED
HISTORY FOR NIPPLE DISCHARGE
Could this lump be mastitis related to lactation?
Key Questions
l
Have you recently given birth?
l
Are you currently breastfeeding or breast suckling?
l
Are your nipples sore or cracked?
l
Have you had pierced nipples?
l
Is your breast painful or hot? Are there any areas of
redness?
l
Have you had a fever?
Childbirth
Engorgement or congestive mastitis begins on day 2 or
3 after delivery and affects both breasts. A breast mass
A focused history can help sort out the causes of the
most frequently presenting cases of nipple discharge.
Questioning should address normal lactation, high circulating levels of prolactin, and malignancy.
Is this normal lactation?
Key Questions
l
When was your last normal menstrual period? How
frequent are your cycles?
l
Is it possible that you are pregnant? What are you
using for birth control?
l
When was your last delivery or miscarriage? How
long were you pregnant?
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l
Did you breastfeed? For how long? When did you stop?
l
Is the nipple discharge clear or milky?
l
How long have you had the nipple discharge?
Chapter 6 • Breast Lumps and Nipple Discharge
Menstrual Cycle
Frequently, brocystic breast changes are most marked
just before menses and manifest as a spontaneous multiple duct discharge that can be either unilateral or bilateral.
Pregnancy and Lactation
Pregnancy is the most common cause of breast tenderness and clear or milky nipple discharge (galactorrhea).
A bloody nipple discharge during pregnancy is usually
the result of vascular engorgement and clears within
weeks. Recent pregnancy and/or breastfeeding (within
8 weeks) can account for a prolonged, clear, or milky
discharge that is successfully suppressed by decreased
breast stimulation or by the administration of dopamine
agonist therapy (bromocriptine or pergolide). If the
patient has had prolonged lactation, there can be milk
formation even though prolactin levels are normal.
Color of Discharge
Normal lactation produces a discharge that is milky
and nonpurulent. Mastitis associated with breastfeeding
can produce purulent discharge. A subareolar abscess
can also produce a purulent discharge. Mastitis and
abscesses that produce purulent nipple discharge must
be distinguished from inammatory breast cancer by
biopsy, or by evoking remission with antibiotic therapy.
Oral contraceptives can cause a clear, serous, or
milky discharge from single or multiple ducts. Ductal
ectasia and papillomatosis can produce a greenish or
brownish nipple discharge. A serous or serosanguineous discharge from a single duct is usually indicative
of an intraductal papilloma, but can be from an intraductal cancer. A bloody nipple discharge can occur
with benign or cancerous conditions.
Duration of Discharge
Women who breastfeed sometimes experience a milky
discharge long after the termination of nursing. Newonset discharge in a woman, who is not pregnant or
lactating, requires further investigation.
Is the discharge related to high prolactin levels?
Key Questions
l
What medications are you taking?
l
Do you jog or run? If yes: Do you wear a sports bra?
Do your nipples rub on your clothing?
l
Are your breasts fondled, squeezed, or suckled during
sexual activity?
l
Do you have a thyroid condition?
l
What medical conditions or health problems do
you have?
l
If a newborn: Has the discharge been present since
birth?
Medicines
Patients taking multiple tranquilizing medications are
often found to have nipple discharge. Discontinuation of
the medication(s) usually eliminates most clear, or milky,
bilateral nipple discharge. However, the condition might
not warrant a drug cessation trial. See Box 6-2 for
medications that can produce nipple discharge.
Behavioral Activities
Nipple stimulation (sexual or during jogging) increases
prolactin levels, as does the use of marijuana. Only
about 13% of men with hyperprolactinemia will develop
gynecomastia and galactorrhea. Women with increased
prolactin levels commonly experience both galactorrhea
and amenorrhea.
Other Causes of Galactorrhea
Certain genetic disorders, medical conditions, and central nervous system (CNS) lesions can be responsible
for galactorrhea.
l
Genetic disorders: Chiari-Frommel syndrome,
Argonz-del Castillo (Forbes-Albright) syndrome
Box 6-2
Drugs That Can Produce
Nipple Discharge
ESTROGENS OR DRUGS THAT INCREASE ESTROGEN
• Digitalis
• Marijuana
• Heroin
DOPAMINE RECEPTOR BLOCKERS
• Phenothiazines
• Haloperidol
• Metoclopramide
• Isoniazid
CNS DOPAMINE DEPLETERS
• Tricyclic antidepressants
• Reserpine
• Methyldopa
• Cimetidine
• Benzodiazepines
Chapter 6 • Breast Lumps and Nipple Discharge
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65
l
Medical conditions: chronic renal failure, sarcoid-
osis, Schüller-Christian disease, Cushing disease,
hepatic cirrhosis, hypothyroidism
l
CNS lesions: pituitary adenoma, empty sella, hypo-
thalamic tumor, head trauma
Newborn
The breasts of a newborn can be abnormally enlarged
secondary to the effects of maternal estrogens. A dis-
charge that is usually white can be present, and is com-
monly referred to as witch’s milk.
Can the nipple discharge be a sign of malignancy?
Key Questions
l
Is the nipple discharge spontaneous or must it be
expressed?
l
Does it come from one or both nipples?
l
Does it come from one or multiple nipple ducts?
l
Do you also have a breast lump?
l
Are you postmenopausal?
Spontaneous versus Expressed Discharge
Spontaneous discharge is more concerning than expressed
discharge. Bilateral spontaneous discharge is likely re-
lated to lactation or systemic causes (e.g., hyperprolac-
tinemia). Unilateral spontaneous discharge is associated
with intraductal papilloma or cancer.
Unilateral versus Bilateral Discharge
Unilateral discharge is usually associated with an intra-
ductal papilloma or cancer. Bilateral breast ndings
seldom represent cancer.
Single-Duct versus Multiple-Duct Discharge
Single-duct involvement is more suspicious for intra-
ductal papilloma or cancer. Multiple-duct discharges
usually are caused by hyperprolactinemia or duct ectasia.
Associated Mass
An associated mass could be benign or malignant.
Further evaluation is mandatory. Ultrasonography is
helpful in differentiating solid from cystic lesions and
is often the rst step in the evaluation of a cyst, or a
mass, in the woman with rm, dense, breast tissue.
Postmenopausal
Postmenopausal women have a higher incidence of
breast cancer. Other risky signs for a cancerous cause
of nipple discharge are presence of a mass or lump,
unilateral nipple discharge, abnormal cytology, and an
abnormal mammogram.
Nipple discharge that is spontaneous, unilateral, and
from a single duct is suspicious for a cancerous etiology.
DIAGNOSTIC REASONING: FOCUSED
PHYSICAL EXAMINATION
Perform a multiposition physical examination of the
breasts and nipples. See the Evidence-Based Practice
box on the effectiveness of CBE.
Inspect Breasts and Nipples
Inspect the breasts while the patient is sitting with her
arms at her sides, arms pushing down on hips (to contract the pectoralis muscles), arms elevated above the
head, and while the patient is bending forward from the
waist (gravity pulling on breast tissue). Look for
changes in breast shape or contour, a lump, or dimpling. Contraction of underlying muscles in the different arm positions will accentuate skin ndings caused
by a xed adherent lesion characteristic of cancer.
Look for breasts that are notably asymmetrical. The
skin over the lesion could then atten or dimple inward, or the nipple could be directed differently than
the nipple of the opposite breast. Normal nipples are
everted and point in like directions. Lifelong inversion,
EVIDENCE-BASED PRACTICE
Detecting Breast Cancer
In this systematic review of randomized clinical trials, the authors estimated CBE sensitivity at 54% and specificity at 94%.
The ability of CBE to detect breast cancers missed on screening mammograms ranged from 3% to 45%. The lack of standardized examination techniques contributed to differences in
findings among clinicians. Longer time spent in performing
CBE and use of specific techniques were associated with
Reference: Barton MB, Harris R, Fletcher SW: Does this patient have breast cancer? The screening clinical breast examination: Should it be done? How?
JAMA 282:1270, 1999.
Effectiveness of Clinical Breast Examination in
greater accuracy. The authors concluded that CBE should be
performed as part of screening for breast cancer. The authors’
bottom line for the CBE procedure: position the patient properly; use a vertical-strip pattern covering all breast tissue; make
circular motions with the pads of the fingers, depressing tissue
with light, medium, and deep pressure; and spend at least
3 minutes examining each breast.
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Supraclavicular nodes
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Chapter 6 • Breast Lumps and Nipple Discharge
either unilateral or bilateral, is also normal, but a new
inversion is suspicious. Engorgement (congestive mastitis) involves both breasts, which are enlarged and
tense. Infectious mastitis usually involves one lobe or
a quadrant of one breast.
Observe Skin of Breasts and Nipples
Observe skin color for erythema and unilateral prominent blood vessels, which may be a presentation of
breast cancer. Prominent vessels, plus a tender cordlike
vein, suggest thrombophlebitis of the supercial veins
of the breast. Both conditions require a CBE and a mammogram to look for a mass. Paget disease begins as a
scaling eczematoid area on the nipple and progresses to
a deep lump behind the nipple well. Paget disease can
produce darkly pigmented lesions that are suspicious for
malignant melanoma. An excisional, or punch biopsy is
recommended to distinguish Paget disease from malignant melanoma or other ulcerative lesions like Bowen
disease, eczema, or papillomatosis. Observe the condition of the skin of the nipples for cracks or dried exudate
or the presence of nipple attening or retraction.
Palpate Breasts With Patient Sitting
Stand in front of the patient and place the palm of
your right hand at the patient’s right clavicle at the
sternum. Sweep downward from the clavicle to the
nipple, feeling for supercial lumps. Repeat the
sweep until you have covered the entire right chest
wall. Repeat the procedure using your left hand for
the left chest wall.
Perform bimanual digital palpation. Place one hand,
palmar surface facing up, under the patient’s right
breast. Position your hand so that it acts as a at surface against which to compress the breast tissue. With
the ngers of the other hand walk across the breast
mound, feeling for lumps as you compress the tissue
between your ngers and your at hand. Repeat the
procedure for the other breast.
If the woman has augmentation of breast tissue,
small masses, including those from ruptured implants,
can best be felt with the patient in the sitting position.
Palpate Lymph Nodes
Palpate the supraclavicular, infraclavicular, and axillary lymph nodes (Figure 6-1). The supraclavicular
lymph nodes can be accessed by having the patient
shrug her shoulders; then feel deep in the supraclavicular hollow. Feel for lymph nodes, noting their size,
shape, consistency, and mobility. The presence of a
small (less than 1 cm), single, rubbery, and mobile
lymph node can be a sign of inammation; rarely is it
Lateral
axillary
(brachial)
nodes
Subscapular
Anterior axillary
(pectoral) nodes
subdiaphragmatic
nodes and liver
FIGURE 6-1 Six groups of lymph nodes accessible to palpation. (From Ball JW, Dains JE, Flynn JA, et al:
Seidel’s guide to physical examination, ed. 8, St. Louis, 2015, Mosby.)
Interpectoral
(Rotter) nodes
Midaxillary
nodes
nodes
Pathways to
Subclavicular
(infraclavicular) nodes
Internal mammary
nodes
Cross-mammary pathways
to opposite breast
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67
a sign of early malignancy. However, nding one or
more lymph nodes in the same region that are greater
than 1 cm, rm, xed to the chest wall, or of a matted
consistency is highly suggestive of metastatic disease.
Palpate Breasts and Nipples With Patient Supine
With the patient supine, ask her to position one arm
above her head. Place a small towel behind the scapula
to aid in attening the breast tissue. Palpate all areas of
breast tissue, feeling for lumps or nodules. Remember
that the breast tissue extends from the second or third
rib to the sixth or seventh rib, and from the sternal
margin to the midaxillary line. It is essential to include
the tail of Spence in palpation. Recall that the greatest
amount of glandular tissue lies in the upper outer quadrant of the breast, with tissue extending from this quadrant into the axilla, to form the tail of Spence.
Palpate using your nger pads, because they are
more sensitive than your ngertips. Palpate systematically, pushing gently but rmly toward the chest, with
your ngers rotating in a clockwise or counterclockwise pattern. At each point, press inward using three
depths of palpation: light, then medium, and nally
deep palpation. Strip, concentric circle, or wedge
methods are commonly used for ensuring palpation of
the entire breast. The vertical strip method has evidence of greater accuracy. Be sure that every part of
the breast is palpated. Regardless of the method, glide
your ngers from one point to the next. Avoid lifting
your ngers off the breast tissue, because doing so
makes it easy to miss tissue.
Assess Nipple Well
At the completion of the examination, return to the
nipple, and with two ngers gently depress the tissue
inward into the well behind the areola. Your ngers
and tissue should move easily inward. A normal nipple
well is a smooth concave structure. Most lumps in this
area are found at the areola border. Repeat with the
other breast.
Examine Nipple for Discharge
Palpate for discharge only if the patient presents with a
report of nipple discharge. Place the thumb and rst
nger 1 to 2 cm outside the border of the areolar complex, and gently compress, sliding the ngers toward
the nipple in a milking fashion. Repeat this maneuver
twice, cephalocaudally and laterally. Determine if the
discharge is unilateral or bilateral. Look closely to determine if the discharge is from a single duct or multiple ducts. Palpation of a single site on the areola border
may reproduce the discharge, and reveal the responsible duct. Specimen collection is often easier, and of a
larger quantity, when the patient is sitting.
Inammatory symptoms and a purulent nipple dis-
charge are suggestive of a breast abscess.
Transilluminate Breast Masses
Transillumination of a breast mass (best performed in
a darkened room) sometimes provides diagnostic clues.
A uid-lled cyst will transilluminate, whereas a solid
mass will not. A solid lump is more frequently a malignant mass, whereas a cystic, uid-lled lump is more
commonly benign.
Characterize Lumps
Accurately measure any lumps by marking the edges
with a pen, and measure the width and length with a
centimeter ruler. Estimate the depth of the lesion, contour, shape, uctuation, rmness, and mobility.
Fluctuation can be determined by holding the edges
of the mass against the chest wall and pressing the
center with nger pads. Fluctuation (“bouncy” consistency) occurs with cysts, lipomas, and abscesses. Cysts
are frequently tender, especially premenstrually. Reexamination in 1 or 2 weeks will usually demonstrate
cyclic hormonal changes of the tissue, and lump size
and tenderness will have changed. In the postmenopausal woman, hormone replacement therapy can
stimulate similar symptoms of breast lumps and pain
(mastodynia). A single, rm, asymmetrical, immobile
mass in a postmenopausal woman will, when biopsied,
prove to be cancerous 75% of the time.
LABORATORY AND DIAGNOSTIC STUDIES
The diagnostic accuracy of ultrasound, mammography,
and aspiration biopsy ranges from about 70% to 80%,
and varies with the training and skills of the clinician
or technician. Therefore, a high degree of suspicion for
cancer and excellent patient follow-up should be sustained for a breast lump or nipple discharge.
Ultrasound
Ultrasound is helpful in differentiating solid from cystic
lesions. In women under age 30 years, ultrasound is often the rst step in the evaluation of a cyst or a mass.
The ultrasound nding of a cystic lesion can be followed
by aspiration of the cyst, eliminating it to make sure it is
not concealing another abnormal breast nding. The ultrasound identication of a solid mass can be followed
by tissue biopsy.
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Chapter 6 • Breast Lumps and Nipple Discharge
Mammography: Diagnostic
In the presence of a palpable mass or nipple discharge,
a diagnostic mammogram is necessary to identify palpable lumps or abnormal screening mammograms. It
consists of additional views to clarify the features and
location of palpable masses. Additional views could
include spot compression, magnication, exaggerated
craniocaudal (CC) to the medial or lateral side, tangential, and 90-degree lateral views. Mammography is of
less diagnostic value in women younger than age 30
because of the density of the breast tissue.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is used primarily
to evaluate abnormal areas that are seen on a mammogram, and to assess breast implants for leaks or ruptures. MRI is sometimes useful in viewing breast abnormalities that can be felt, but are not visible with
mammography or ultrasound. It also can be used to
image dense breast tissue, which is often found in
younger women. Contrast is used to enhance the vascularity of malignant lesions. Although MRI is highly
sensitive (85% to 100%), it lacks specicity. MRI is
inferior to mammography in detecting in situ cancers
and cancers smaller than 3 mm. The role of MRI in the
evaluation of nipple discharge is evolving.
Fine Needle Aspiration and Cytological
Examination
Fine needle aspiration (FNA) biopsy uses a smallgauge needle to obtain uid and cellular material. FNA
is a routinely performed ofce procedure that is both
diagnostic and therapeutic. It immediately determines
if the lump is a cyst or a solid tumor. The aspirate is
sent for cytological evaluation to determine the presence or absence of malignant cells. If cytology ndings
of the aspirate are negative, the mass completely goes
away, and is not present on follow-up examinations, no
further treatment is necessary.
Stereotactic or Needle Localization Biopsy
Fine needle aspiration can also be used with ultrasonography or stereotactic imaging to further assess and
obtain adequate sampling in poorly dened palpable
masses. The lesion is located, marked, and veried by
imaging to assist in the identication of the tissue to be
sampled.
Core Needle Biopsy
Core needle biopsy (CNB) uses a large-gauge needle to
obtain several cores of tissue. It produces a larger tissue
sample than FNA. It can be used in conjunction with
ultrasonography or stereotactic imaging for small or
difcult to palpate lesions. Local anesthesia is required.
Excisional Biopsy
Excisional biopsy is the gold standard for evaluating
breast masses. It is performed in an operating room
using local or general anesthetic and the entire lesion is
removed. Excisional biopsy is indicated if there is a
large breast mass or for those lesions in which more
conservative biopsy has produced equivocal results.
The surgical specimen is evaluated histologically.
Microscopy
Microscopy of nipple discharge can reveal fat cells of galactorrhea, leukocytes of infection, or red blood cells. Care
must be taken to prevent the slide from drying out. Place a
coverslip on the slide immediately after obtaining the
specimen and review the slide shortly after it is prepared.
Cytological Smear
A cytological specimen of discharge is placed directly
from the nipple onto the slide, or if there is only a small
amount of discharge, it can easily be collected with a
saline-saturated cotton-tipped applicator and spread
onto the slide. The slide is then xed in the same manner as a cervical specimen. This technique can expose
cancerous cells. However, a smear with negative
ndings is not conclusive and additional workup is
mandated.
Ductography (Ductogram)
A ductogram is useful in evaluating the cause of nipple
discharge. Contrast medium is injected into the discharging duct, followed by a mammogram. The mammogram
may show a lling defect (commonly an intraductal papilloma), a dilated or cystic appearance (duct ectasia or brocystic disease), or an abrupt obstruction (malignancy).
Serum Prolactin Level
Elevated serum prolactin levels can produce nipple
discharge. Hyperprolactinemia should be suspected
when the prolactin level exceeds 20 to 25 ng/mL. Prolactin elevation, secondary to medications, is generally
less than 100 ng/mL. Prolactinomas are found when
the prolactin level exceeds 150 ng/mL.
Thyroid Function Testing
Thyroid-stimulating hormone (TSH) is high in hypothyroidism. About 20% of patients with hyperprolactinemia have hypothyroidism. TSH testing is done to
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