GESTATIONAL AND PLACENTAL DISORDERS.
PATHOLOGY OF BREAST.
PATHOLOGY OF PREGNANCY. TROPHOBLASTIC NEOPLAMS.
Diseases of pregnancy and pathologic lesions of the placenta may result in
abortion, congenital malformation, intrauterine or perinatal death, maternal
death
 ECTOPIC PREGNANCY
-is a pregnancy in which implantation of fertilized ovum occurs at a site
other than the uterine cavity
most common type of ectopic pregnancy is tubal pregnancy
-represents about 0.5% of all pregnancies
-in most cases - no etiologic factors can be identified,
in other cases of tubal pregnancy- in women with pelvic inflammatory
lesions, peritoneal adhesions, tubal narrowing, endometriosis involving the
uterine tube
pathology:- the ovum develops normally in first few weeks, later development is
greatly influenced by the lack of space and poor vascular supply
-rupture of the tube occurs 2-6 weeks after fertilization-massive
intraperitoneal hemorrhage- in most cases the released embryo dies soon after
rupture of the tube, very rarely secondary implantation in abdominal cavity may
occur
-in some cases- the tube does not rupture- calcification of the fetuslithopedion-"stony child" or the embryo dies and is absorbed
Clinical features -patients with tubal pregnancy- present with positive pregnancy
test, and absence of uterine enlargement
-rupture of the tubal pregnancy- abdominal pain, rapid and severe
abdominal bleeding-hypovolemic shock
Diagnosis of tubal pregnancy: -absence of chorionic villi in endometrial
curretings performed for vaginal bleeding
 SPONTANEOUS ABORTION -delivery of the embryo or fetus before 20
weeks is termed abortion- after 20 weeks- it is called premature delivery
- incidence: -spontaneous abortions are common-the clinical incidence is
about 15 %, but real incidence may be as high as 40-80% of fertilized ova
etiologic factors- many, such as infections- rubeolla, toxoplasmosis, listeria,
cytomegalovirus
-mechanical factors- uterine leiomyoma, cervical incompetence, etc
-endocrine, immunologic- autoimmune diseases, ABO incompatibility
-congenital chromosomal abnormalities
-spontaneous abortion is recognized-by vaginal bleeding, by lower abdominal pain
pregnancy tests become negative,
-incomplete abortion- when products of conception are retained in the uterus
(chorionic villi, trophoblast)-this may cause continuous bleeding-curretage
 MATERNAL COMPLICATIONS OF PREGNANCY
1-amniotic fluid embolism-amniotic fluid and debris may entry the
uterine veins at the time of placental separation in labour and travel in the
maternal circulation as emboli-though amniotic fluid embolism is rare, it accounts for a significant
percentage of maternal deaths in developed countries, where
maternal
mortality rate is very low- predisposing factors for amniotic fluid embolism arepremature placental separation and dead fetus
pathological findings:-amniotic debris, squames may be found in the lungs
-amniotic fluid contains thromboplastic substances-results in DIC- main clinical
symptoms
2-rupture of the uterus -factors predisposing to the rupture include
placental abnormalities, fibrous scars from previous cesarian sections,
malposition of the fetus, and prolonged labor
3- ecclampsia -is a syndrome consisting of three major clinical symptoms
-gestational edema, proteinururia and hypertension- "EPH gestosis" is
used
-eclampsia complicates about 5% of pregnancies
-predisposing factors-occurs more commonly in first pregnancies- primigravida
status, in multiple pregnancies and in an excess of amniotic fliud (called
hydramnios), in preexisting diabetes mellitus and hypertension, in malnutrition,
in hydatidiform mole
etiology-the cause is unknown- theories include- placental ischemia,
immunological reaction against placental vessels, deficient production of
prostaglandin E by placenta
pathogenesis: - deficient secretion of prostaglandins E by placenta results in
activation of renin-angiotensin system- systemic hypertension and development
of DIC due to substances with thromboplastic activity released by the placenta
pathology: -the placenta shows regressive changes, such as congestion, foci of
calcification, hyaline deposits, placental infarcts
-the maternal decidua shows hemorrhage and necrosis due to thrombosis of
arteries
-consequencies of DIC- hyaline thrombi in multiple capillaries, signs of
hemorrhagic diathesis
-maternal kidney-foci of cortical necrosis, regressive changes of
glomerular endothelial cells, hemorrhages -proteinuria, renal failure
-maternal liver- congestion, centroacinar necroses -icterus
-brain, heart, lungs-hemorhages, -convulsions, clonic contractions
treatment: reduction of blood pressure, antihypertensive drugs, induction of
labor or cesarian section is necessary in some cases
PATHOLOGY OF THE PLACENTA
 -placenta praevia -the fertilized ovum normally implants in the fundus- and
placenta develops at this location
-abnormally low implantation may result in formation of the placenta in the lower
uterine segment -it is called placenta praevia
-causes problems in late pregnancy and in delivery- at the onset of
delivery- labor causes severe bleeding- antepartum hemorrhage -treatment by
cesarian section
 -abruptio placentae -is a premature separation of the normally situated
placenta after 20 weeks of gestation
-causes antepartum bleeding due to rupture of the vessels between
myometrium and separated placenta -in 20% of cases- blood may be retained in
the placental bed- concealed hemorrhage - excessive blood loss may result in
DIC or posthemorrhagic shock
-in other cases- severe vaginal bleeding- revealed hemorrhage
 - placenta accreta -refers to a condition in which placental villi adhere to the
underlying myometrium, morphological variants include placenta increta-when
the villi invade only myometrium and placenta percreta- when there is villous
infiltration through the whole thickness of the uterus
-normally- placental villi are separated from the myometrium by a plate of
decidual tissue -placenta accreta occurs in an absence of the plane of separation
between the placental villi and myometrium- thus, placenta fails to separate in
labor-causes severe postpartum hemorrhage -hysterectomy is frequently
necessary to stop postpartum bleeding
 -placental infection -there are two types of infection of the placenta
1- more commonly the infections of the placenta are due to organisms
that ascend from the maternal vaginal tract- often associated with premature
rupture of the membranes
grossly: the placental surface is cloudy, -histologically: chorionamnionic
membrane shows diffuse leukocytic infiltration, edema and congestion choriamnionitis 2 - maternal hematogenous infections - infections reaching the placenta
through the maternal bloodstream - involve the placenta and cause inlfammation
within the chorionic villi- villitis, abscesses, granulomas
among the most frequently recognized agents of villitis are- toxoplasmosis,
syphilis, tuberculosis, various viral infections
 TROPHOBLASTIC DISEASE - there is a group of diseases related to normal
or abnormal gestation that have as a common feature proliferation of
trophoblast
-individual disorders differ remarkably in appearance and clinical
significance
they include: hydatidiform mole-complete, partial and invasive, -placental site
trophoblastic tumor and choriocarcinoma
-hydatidiform mole= molar pregnancy -represents a noninvasive
abnormal placenta characterized by grossly evident hydropic swelling of
chorionic villi accompanied by trophoblastic proliferation
-it occurs in one in every 2000 pregnancies, benign
etiology:-two distinctive subtypes are recognized - complete and partial molecytogenetic studies have shown that chromosomal abnormalities play a key role
in the development of both complete and partial mole
-complete mole- never contains fetal parts - all the chorionic villi are
abnormalpathology:-the uterus is enlarged, uterine cavity is filled with a mass of
grapelike structures- thin-walled translucent cystic edematous chorionic villithat represent hydatidiform mole
microscopically- the cysts are composed of dilated edematous chorionic villifilled with avascular myxoid loose stroma- there is always trophoblastic
proliferation with cytologic atypia
-greatly elevated levels of chorionic gonadotropin- regress to normal levels
after removal of the mole
clinical features: pregnancy, amenorrhea, vomiting, positive pregnancy test,
uterine enlargement greater than in normal pregnancy, vaginal bleeding, high
level of HCG
-partial mole -contains fetal parts-has some normal chorionic villi-partial mole represents about 15-30% of all moles- the fetus is anomalous
pathology: the volume of placental tissue is normal-the uterine size is nearly
always small or appropriate for the gestational age- serum HCG level is not
elevated more than in normal pregnancy -the risk for trophoblastic neoplasms is
lower than in complete mole
-invasive mole -refers to a hydatidiform mole, in which villi and
trophoblast penetrate into the myometrium and/or the blood vessels of the
myometrium,
-leads to persistent bleeding
-biologically, an invasive mole is intermediate between benign and malignantlocally aggressive, but no metastatic potential -associated with necrosis and
hemorrhage in the myometrium -vascular invasion may result in trophoblastic
nodules outside the uterus-villi may embolize to the lungs- may regress
spontaneously
-associated with persistent elevation of HCG levels after evacuation of the
uterine cavity
without treatment- mortality rate would be high- from hemorrhage or uterine
rupture
treatment includes chemotherapy, and sometimes hysterectomy is necessary
-choriocarcinoma -highly malignant tumor derived of trophoblast, rare
complication of pregnancy, about half of cases follow a hydatidiform mole,
others occur after ectopic pregnancy or abortion
-it is a very aggressive malignant tumor arising of gestational trophoblast
pathology: grossly- presents as a friable hemorrrhagic tumor in the
uterine cavity, it infiltrates the myometrium - very early vascular invasionmetastases occur early in lungs, brain, bone marrow
microscopically: choriocarcinoma is composed of cytologically malignant
cells of cytotrophoblast and syncytiotrophoblast differentiation
clinical features: -the patients present with uterine bleeding, within few
months after normal pregnancy, abortion or hydatidiform mole -serum HCG is
elevated
-diagnosis is established by histological examination of biopsy from the uterine
cavity
prognosis: good response to aggressive chemotherapy -nearly 100% of
patients are cured- if the neoplasm did not spread beyond the uterus, lungs and
vagina
about 70% of patients may be cured in widely disseminated disease
-placental site trophoblastic tumor- rare tumor composed of neoplastic
intermediate trophoblastic cells, no chorionic villi or fetal parts are identified
pathology: grossly:-the lesions range from microscopic to diffuse huge tumors,
tumors are often well defined, project into the uterine cavity
microscopic findings:- tumors is composed of intermediate trophoblast cellsinfiltration of the myometrium -neoplastic cells contain human placental
lactogen, no HCG, but contain cytokeratins
biological behavior: the tumor tends to have an indolent behavior, some cases
may have more aggressive behavior (about 15%)- higher mitotic activity, larger
cells, more apparent cytological polymorphism
-placental site nodule and plaque- discrete foci of intermediate
trophoblastic cells surrounded by hyalinized material - detected incidentally in
the endometrium or myometrium in curretage performed for abnormal bleeding
-benign, no recurrences
PATHOLOGY OF BREAST.
 INFLAMMATORY BREAST LESIONS
-acute mastitis and breast abscess formation- occurs commonly in the
postpartum period- cracks in the nipple -potential route of bacteria (stasis of
the milk)
-staphylococcus aureus-the most common infecting agent
grossly: redness of the skin, swelling, pain, tenderness
-chronic mastitis- chronic inflammation of the breast is uncommon
-it occurs in perimenopausal women as a result of obstruction of the lactiferous
ducts by secretions
histologically: the lesion is characterized by -mammary duct ectasia- involved
ducts are dilated
-periductal inflammation- plasma cell mastitis
-in other instances- rupture of small ducts- release of the secretions into the
stroma- cellular reaction with accumulation of foamy macrophagesgranulomatous mastitis
grossly: iregular fibrosis with induration of the involved area- may cause nipple
retraction- mimics symptoms of breast cancer
-fat necrosis
-is uncommon, but important lesion, because this may produce large and
sclerosing masses- thus the lesion may mimick macroscopically breast cancer
-cause is unknown, or trauma or ischemia (in large pendulous breasts)
-in early stage- fat necrosis is characterized-by accumulation of neutrophils and
histiocytes
-later- replaced by granulation tissue - numerous foamy histiocytes-grayishwhite firm lesion BENIGN PROLIFERATIVE EPITHELIAL BREAST LESIONS:
-fibrocystic disease-is characterized by combination of cyst
formation, epithelial hyperplasia and/or stroma fibrous overgrowth
-grossly: FCD often produces palpable breast mass
-pathogenesis : FCD results from response of the breast to cyclic changes in
levels of oestrogen and progesterone- it is unusual before 20 years of age, most
commonly seen between ages of 25 to 40 years
-histologically -there are two dominant morphologic patterns:
1-cyst formation and fibrosis without epithelial hyperplasia- simple
fibrocystic disease- most common, is not associated with higher risk of cancer
-the changes consist of increased synthesis of collagen, increased amount of
fibrous connective tissue, that compresses the acini and ducts
-typically there are large cyst lined by flattened epithelium
2-FCD with epithelial cell hyperplasia- proliferative fibrocystic
disease
-there is combination of cyst formation and papillary proliferation of the ductal
or lobular epithelium
-there may be dysplasia in the epithelium- atypical hyperplasia- these types of
FCD are associated with 4-5fold increased risk of cancer
clinically : patients with fibrocystic disease present with pain, nipple discharge
and palpable mass in the breast-necessary to rule out carcinoma- biopsy
-sclerosing adenosis- is characterized by increased fibroblast activity and
collagen production in the involved lobules- mammary ducts are compressed,
distorted,
-the lesion is benign, likely associated with increased risk of cancer
-atypical ductal hyperplasia- characterized by proliferation of ductal
epithelium with atypia-slightly increased risk of development of carcinoma
 BENIGN TUMORS
1. fibroadenoma
-is the most common benign tumor of the female breast
-occurs at any age within the reproductive period-highest incidence in young
women before 30 years of age
-grossly- freely movable, well circumscribed, firm nodule
-on section the tumors is uniformly grayish-white, firm nodular
-usually between 1-5 cm in diameter
histologically- fibroadenoma is characterized by proliferation of both glandular
and stromal elements-the tumor exists in two variants- pericanalicular and
intracanalicular fibroadenoma -often overlapping patterns
-pericanalicular-fibroblastic hypercellular stroma encloses glandular and
cystic epithelial spaces in concentric manner
-intracanalicular-connective tissue stroma reveals more active
proliferation with compression of the epithelial structures, glandular lumina are
compressed into narrow strands or slitlike irregular clefts
-infrequently, FA may grow to very massive proportions -called giant
fibroadenoma
2. phyllodes tumor
-large bulky tumor lobulated and cystic- they have been designanted
cystosarcoma phyllodes - the lesion can be both benign and malignantgrossly: lobulated, cystic tumors, the tumor may cause a distortion of the
breast- produce a bulky mass, even pressure necrosis of the overlying skin- this
clinical behavior does not imply malignancy
histologically: more cellular myxoid stroma than in fibroadenomas
-increased stromal cellularity, high mitotic activity and anaplasia- imply more
aggressive clinical behavior and transformation to malignancy -rapid increase in
size and invasive growth to adjacent breast tissue
3. lactating adenoma
-the patients are young- pregnant or nursing
-associated with rapid increase in size- benign -may be even multiple
histologically composed of well differentiated glandular structures- lobular
arrangement, well-circumscribed by fibrous capsule
4. intraductal papilloma
-benign tumor originating in a major lactiferous duct- presents with bloody
nipple discharge -most are less than 1 cm in diameter
grossly-papillary mass projecting into the lumen of a large duct
-papillomas are generally solitary
-located in the subareolar region
-most commonly during the fifth and sixth decade of life
histologically- numerous delicate papillae composed of fibrovascular stroma and
covered by a layer of epithelial and myoepithelial cells -epithelial cells line the
luminal aspect of the papillae and a myoepithelial cell layer is invariably present
between the epithelial cells and the basement membranes
5.intraductal papillomatosis
-is defined as a proliferation of papillary fronds supported by fibrovascular
stalks within multiple terminal duct-lobular units
-patients are younger than those with solitary papillomas- nipple discharge in
about one third of patients
-clinically- in some cases accompanied by atypical ductal hyperplasia and
increased incidence of cancer
 MALIGNANT TUMORS
1. Carcinoma of the breast
-common- breast cancer is second most common malignancy in women, the term
breast cancer implies carcinoma arising in the ductal or lobular epithelium of the
breast
 incidence: rarely develops before the age of 25 years, age peak during
perimenopausal years.
 risk factors: positive family history, long reproductive life- means eyrly
menarché and late menopause, more frequent in nulliparous than in
multiparous women, exogenous estrogens for treatment of menopausal
symptoms- increase somewhat a risk of breast cancer, oral contraceptive not
associated
 classification- two major categories- invasive (infiltrating) and noninvasive
most tumors are invasive, careful examination and screening mammographyincreases a number of in situ tumors
 Features common in all invasive carcinomas
-local invasion into adjacent structures- tumor fixation, retraction of the nipple,
dimpling of the skin
-lymphatic invasion-causes lymph node metastases- about two-thirds of breast
carcinomas present with lymph node metastases-axillary, supraclavicul and
mammary nodes always involved
blood vessel invasion- metastases to the skin, lung, liver, bone marrow, etc.
 clinical features:
factors influencing the prognosis-tumor size- minimal cancer is less than 1 cm, most tumors are detected
4cm in diameter
-lymph node spread and number of positive nodes- two thirds of breast
cancers are detected as lymph node positive- 5year survival for lymph node
negative patients-80%, for positive patients only 50%
-histological grading- degree of differentiation, nuclear polymorphism,
mitotic count
-estrogen/progesterone status-70% breast cancers contain ER/PR
-proliferative activity-presence of activated gene-c-erbB-2/HER2neu -aggressive behavior
1. ductal carcinoma - the most common type of breast carcinoma-over
90% of breast ca arise in the ducts
- may exist as ductal carcinoma in situ or invasive
-noninvasive type = carcinoma in situ -tumor restricted to
intraductal proliferation without penetrating the basement membranes of
ducts- ducts may be dilated and filled with carcinoma cells- sometimes central necroses with comedo-like appearance -called
comedocarcinoma
-invasive ductal carcinoma
-grossly- the tumor is poorly defined, firm, palpable mass -hard consistency
-some tumors exhibit marked fibroplasia- increased production of dense fibrous
tumor stroma- desmoplastic carcinoma-skirrhus
-infiltrative attachment to adjacent structures, fixation to the pectoral fascia,
dimpling of the skin, retraction of the nipple
-on section-the tumor is retracted below the cut surface
histologically: tumor consists of anaplastic duct epithelial cells disposed in cords,
solid foci, tubules, glandular and cribriform anastomosing structures, frequent
finding- perineural and intravascular invasion
 clinical prognosis: breast cancer has usually high propensity for dissemination
2. Lobular carcinoma
-characterized by tumor proliferation of epithelial cells with lobular type
of differentiation (loss of E-cadherin expression)
-difficult diagnosis, mammography does not help
-in situ (LCIS) -histologically distinctive entity, true precursor of IDC and ILC
characterized by proliferation in one or more terminal duct-acinar units,
- can be multifocal, bilateral
-composed of the cells having lost cohesion, that are uniform in size, small,
round to oval in shape, with low mitotic rate
-invasive (ILC)- these tumors are of particular interest because they may be
bilateral and/or multicentric within the same breast
grossly: poorly circumscribed, rubbery
histologically: consists of single layered cords of cancer cells infiltrating the
fibroadipose tissue of mammary gland- often with skirrhous pattern -indian file
pattern
- the cells are small, uniform with little cytologic polymorphism
- -3. basal cell carcinoma
-recently characterized breast cancer entity, more common in women with
congenital mutation in BRCA gene
-poor prognosis
- 4. Medullary carcinoma
-this carcinoma is very rare, accounts for less than 1% of all breast carcinomas
- produces larger masses of soft consistency
-on section-soft, fleshy appearance, with foci of necroses and hemorrhages
histologically: carcinoma is characterized by solid sheets of large cell with
vesicular nuclei, frequent mitoses, and by abundant lymphocytic infiltration in
the stroma
-prognosis probably slightly better than that of ductal cancer- 10-year survival
is 70 to 90%
- 5. Colloid (mucinous) carcinoma
-this variant tends to occur in older women
grossly-large gelatinous mass, the tumor is extremely soft
histologically: composed of large lakes of mucinous extarcellular matrix- floating
within the mucin there are small islands of cancer cells
-better prognosis
-6. Paget disease of the nipple
-is a special form of ductal breast cancer that arises in major ducts and extends
to the skin of the nipple
grossly: erosions and exematoid changes of the nipple-with discharge
histologically: the squamous epithelium of the nipple is infiltrated by carcinoma
cells- Paget cells - these cells are large, with pale cytoplasm (mucin in the
cytoplasm), and many mitoses
-careful studies often reveal the presence of ductal invasive or noninvasive
breast cancer
-7. metaplastic carcinoma
-less common type, composed of spindle cells, histologically similar to
mesenchymal tumors
-prognosis poor
-may contain foci of cartilage, squamous metaplasia, etc
PATHOLOGY OF THE MALE BREAST.
1- gynecomastia
-the male breast is subject of hormonal influences-enlargement of male
breast may occur due to stimulation by estrogens- hyperestrogenism
-excess of estrogens may occur in a variety of circumstances, such as
-in puberty or in very old age- owing to relative increase in adrenal
estrogens as the androgenic function of the testis fails
-in testicular tumors with production of estrogens (Leydig cell
tumors, Sertoli cell tumors)
-in cirrhosis- the liver is responsible for metabolism of estrogens
grossly:unilateral or bilateral enlargement of the male breast
histologically: proliferation of dense fibrous stroma and hyperplasia of the
epithelium of the ducts- ductal lining may appear multilayered with papillae
2- carcinoma
-very rare in male breast- in advanced age
grossly: ulceration of the skin more common than in women
clinical behavior-the same as that of the breast cancer in women, including
dissemination