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Pathology
Congenital Anomalies
Polythelia/Supernumerary Nipples: along the milk
line, accessory nipples
Polymastia: accessory true mammary glands and can
undergo the same pathology the main breasts can
Amastia: congenital absence of breast
Congenital inversion of the nipple: can be mistaken for
carcinoma (because some cause retraction)
Macromastia: very large breast which can be treated
by reduction mammoplasty
Micromastia: very small breast which can be treated
by augmentation, implants, TRAM (transverse rectus
abdominis myocutaneous flap)
Galactocele
Cystic Dilation of obstructed duct during
lactation
Is a very painful lump
May get infected with persistent induration
Risk Factors:
Oral contraceptive use decreases the risk
Pathogenesis:
Exaggerated, distorted cyclical changes associated with hormonal changes of
menstrual cycle
Even with the normal breast, there may be some irregularity of texture within
the menstrual cycle
Change is in the stroma where fibrosis occurs along with ductal epithelium
proliferation which can be mild simple to severe atypical
There may or may not be cysts (micro or macro) termed BLUEDOMED cysts
Can be CALCIFIED (shown on mammography) in concretions of secretions or
necrosed epithelial cell heaps (which can often be mistaken for carcinoma)
FCC-Categories
Nonproliferative/Simple FCC:
Proliferative FCC:
Sclerosing Adenosis
Simple
Non-proliferative
FCC
Unruptured
Blue-Dommed
Cyst
Proliferative
Sclerosing Adenosis
Apocrine
Metaplasia
with
eosinophilia
Higher degree
of atypia
(ductal prolif)
with increased
risk of
malignancy
Mild Atypia
Unlike Carcinomas,
here the acini are
arranged in a swirling
pattern and the outer
border is usually well
circumscribed.
The overgrowth of
fibrosis compresses
the lumina of the
acini and ducts ->
solid cords of cells
Types:
Reaction to implants
Paraffin or Silicone can lead to abscess formation or foreign body granulomas
Can eventually lead to fistulae
Fibroadenoma
Commonest benign tumor of the breast in females
Usually appear in young women with the peak in the third decade of life
Pathogenesis:
Absolute or relative increase in estrogen activity is thought to be the contributing factor to its
development
The stromal cells are monoclonal and so represent the neoplastic element of these tumors
Gross Morphology:
All are firm, with a tan-white color on cut section, punctuated with softer yellowish-pink specks
representing the glandular areas
Histology Morphology:
Tumor of stromal cells
Loose and edematous myxoid fibroplastic stroma and ductlike epithelial lined spaces
Pericanalicular pattern: oval ducts surrounded by stroma (ductal spaces are open, round to oval and fairly
regular)
Intracanalicular: compressed by extensive proliferation of the stroma so that on cross-section they appear
as slits or irregular, star shaped structure
Mixed Pattern
Clinically it does not have any different for the type of pattern
Can calcify during after menopause: POPCORN-LIKE CALCIFICATION
Fibroadenoma
~ 7cm
Phylloides Tumor
AKA: Cystosarcoma Phylloides
Thought to arise from the periductal stroma and not from preexisting fibroadenomas
Usually start off as small (3-4 cm) masses but usually grow to
massive (10-15 cm) lobulated and cystic masses (sometimes) and
often distend the breast
On gross cross section, they exhibit leaf-like clefts and slits
On histology: increased stromal cellularity with anaplasia and high
mitotic activity accompanied by rapid increase in size, usually with
invasion of adjacent breast tissue my malignant stroma
Most will remain localized and can be cured by excision but
malignant lesions may recur (again these tend to remain localized)
Only 15% metastasize to distant sites through hematogenous
routes therefore no LN involvement
Phylloides Tumor
Because of the slits, grossly,
can appear lobulated
Leaf Like Clefts/Slits
Stromal Proliferation
Intraductal Papilloma
Neoplastic papillary growth within a duct, most often solitary and unilateral
Found within the principle lactiferous ducts or sinuses
Clinically present:
As a result of the appearance of serous or bloody nipple discharge
As a result of the presence of a small subareolar tumor a few mm in diameter
As a result of nipple retraction (rarely)
Morphology:
Solitary and less than 1 cm in diameter
Delicate, branching growths within a dilated duct or cyst
Histology: multiple papillae, each having a connective tissue axis and fibrovascular
core covered by cuboidal or cylindrical epithelial cells that are frequently double
layered, with the outer epithelial layer overlying a myoepithelial layer
There is no atypia or mitosis
Intraductal Papilloma
Fibrovascular Core
Double Layer
Of Epithelium
(Cuboidal Cells
Over Myoepithelial
Cell)
Breast Carcinoma
Second most common malignancy in women behind lung cancer and accounts for
20% of cancer death in females
Age: over 40 years old and 25% are post-menopausal (rare in males but possible)
Clinically:
Mass, induration, fixation to pectoralis, skin retraction
Lymphedema with skin thickening around the hair follicles (looks like peau de orange)
Site:
Upper outer quadrant 50% of the time, more often on the Left Breast when unilateral
Bilateral 4-10% of the time
LN involvement at time of diagnosis is usually axillary, internal mammary and in later
stages the supraclavicular
Metastasis:
Lungs, bone, liver, adrenals or anywhere else in the body
Can remain dormant after treatment of primary lesion and reappear 15 years later
Diagnosis:
Self inspection and palpation should be done as screening
In high risk individuals, mammography should be done every 1-2 years after age of 40
If lump found, FNAC or lumpectomy should be performed
In recent trials, nipple aspiration, ductal lavage, or random periareolar FNA
Core needle biopsy with vacuum assistance
Advanced breast biopsy instrument (ABBI)
About 5-10% of breast cancers are related to specific inherited mutations and women
are likely to carry a breast cancer susceptibility gene is they develop breast cancer
before menopause
Typically will have bilateral cancer, and have other associated cancers like ovarian
Will have a significant family history with multiple relatives affected before menopause
Certain ethnic groups
Higher incidence in Ashkenazi Jews (usually develop disease 15-20% before sporadic
cases)
DCIS Non-Invasive
Ductal proliferation
With No Invasion of
The Stroma
Ductal Proliferation
Uniform appearance with monomorphic, bland, round nuclei and occur in loosely
cohesive clusters in ducts and lobules
Intracellular mucin vacuoles (signet rink cells) are common
Usually always an incidental finding and does not form masses and is only rarely
associated with calcifications
1/3 of women will develop and invasive carcinoma and can arise in either breast at a
significant frequency (DCIS goes to same breast, unilaterally)
1/3 will become lobular carcinoma but most are of no special type
LCIS Non-Invasive
Hyperproliferation of
Acinar Cells with no
Stromal Invasion
No pleomorphism; No Mitoses; Can wrap around normal or cancerous ducts/acini -> Bulls Eye Pattern
Inflammatory Carcinoma
H&E
Epidermis
Dermis
Crusted Over
Erythema
PAS Stain
Staging:
0: DCIS, LCIS, Padgets with a 92% 5 yr survival
I: Invasive Ca 2 cm or less in diameter without nodal involvement (this includes carcinoma in situ with
microinvasions) (80% 5 yr survival)
II: Invasive Ca 5 cm or less in diameter with up to 3 involved axillary LN or an invasive Ca greater than 5 cm
with no LN (65% 5 year survival)
III: Invasive carcinoma 5 cm or less in diameter with 4 or more axillary LN involved or Invasive carcinoma
greater than 5 cm with nodal involvement; can involve ipsilateral internal mammary lymph nodes or skin
carcinoma (40% 5 yr survival rate)
IV: Any breast cancer with distant metastases (10% 5 yr survival rate)
Male Breast
Gynecomastia
Male analog of FCC
Relative or absolute increase in Estrogen
Liver Cirrhosis, Klinefelters XXY, Estrogen Therapy
Button like nodule beneath the areola
Microscopy: intraductular hyperplasia
Carcinoma
Rare with M:F being 1:125
Rapid Infiltration because less amount of breast
substance in males
Ovarian Disease
The ovaries are affected by physiological changes involving the menstrual
cycle, changes associated with aging and a variety of tumors from its
component tissues
Because pathologies affecting the ovaries are clinically silent for so long (a
log of space to grow within), there is a high lethality associated with them.
They become clinically evident when there is increased pressure or
swelling, pelvic discomfort, heaviness or frequent micturition
There can be hormonal affects, although rare, which include menstrual
irregularities affecting the endometrium, hirsutism, breast enlargement,
etc.
Any of these pathologies can affect the ability for ovulation and can lead to
infertility
Tumors specifically:
Less common that those of the uterus and breasts but produce a higher level of
lethality because of the late detection
4th most common cancer after lung, breast and colon
Pregnancy and Oral Contraceptives REDUCE the risk of ovarian cancer but
INCREASES the risk of Breast Cancer, decreases risk of FCC
Ovarian Cysts
Follicular vs Luteal Cysts
Follicular cysts are lined by layers of cuboidal granulosa cells (UNRUPTURED)
Luteal cysts are hemorrhagic cysts lined with lutinized cells (RUPTURED AND SEALED)
Are often multiple and develop immediately subjacent to the serosal covering of the
ovary
Clinically:
Usually small (1-1.5cm, can reach 4-5 cm) and are filled with clear, serous fluid: larger cysts can be
palpable and usually produce pelvic pain
As fluid accumulates, pressure causes atrophy of these cells and can sometimes rupture producing
intraperitoneal bleeding and acute abdominal symptoms (Secondary to Torsion)
Can also cause endometrial hyperplasia
Diagnosis:
Ultrasound
**Most Common Complication is Torsion Cysts where it turns and causes infarction
(pain)**
Chocolate Cysts:
This is a result of ENDOMETRIOSIS causing repeated cyclical hemorrhage giving the
chocolate appearance
This induces mass amounts of fibrosis, adhesions and pain
Grossly, there are normal looking endometrial glands within stroma plus RBCs and lots
of hemosiderin (Need two of the three for diagnosis)
Cysts can extend along the pelvic ligaments
Usually associated with infertility, and therefore must be distinguished from luteal cysts
for proper and timely removal
Simple Cysts
Gross Morphology:
Ovaries are twice the normal size with a thick, hypertrophied stroma
Ovaries are gray-white with a smooth outer cortex and are studded with subcortical cysts (0.5-1.5 cm)
Histo Morphology:
Thickened fibrotic outer tunica, overlying innumerable cysts lined by granulosa cells with a hypertrophic
and hyperplastic luteinized theca interna
Conspicuous absence of corpora lutea
Hormones: High LH, Low FSH (LH:FSH; 3:1), High Testosterone
Ovaries and adrenals produce excess androgens which are turned into estrogens in the fat which inhibit
FSH release by pituitary
Increased LH:FSH stimulates theca cells to produce more estrogens and the cycle continues
Hyperinsulinemia due to peripheral resistance to insulin
Diagnosis:
Hormonal Assay or Transvaginal US
Treatment:
Hormonally break the cycle
Chlomiphene induces ovulation
In the Past, wedge resection of ovary to help ovulation and reduce the mass (not done anymore)
PCOD
Ovarian Tumors
Very diverse pathologically due to the 3 different cell types that make up
the normal ovary
Multipotential surface (coelomic) covering epithelium
Totipotential germ cells
Multipotential sex cord/stromal cells
Most are neoplasms of surface epithelial origin and their malignant forms
account for 90% of all ovarian cancers
80% of tumors are benign in 20-45 year old women
20% of tumors are malignant in 40-65 year old women
Most often are bilateral, occur more often in nulliparous women, there is
usually a family history, and oral contraceptives reduce the overall risk
Commonest tumor: Epithelial (Serous)
Commonest malignancy: Serous Cystadenocarcinoma
Commonest bilateral tumor: Serous Cystadenocarcinoma (66%),
Metastasis
Spread:
Into the peritoneum and cause ascites or omental pancakes
Into LN (iliac and paraaortic)
Through the blood to the lungs
Pathogenesis:
With repeated ovulation and scarring, the surface epithelium is pulled into the cortex of the ovary,
forming small epithelial cysts
With time these can undergo metaplasia and neoplastic transformation
Behavior:
Benign: Cystadenoma (if they involve the stroma: cystadenofibroma)
Borderline: Intermediate carcinoma of low malignant potential
Malignant Cystadenocarcinoma
Gross Morphology:
Small to very large, filling the abdomen
Benign: Cystic, unilocular, little to no papillae, smooth
Malignant: Solid, multilocular, papillae, nodular
Clinically:
Abdominal pain (not typical unless late/large), swelling, dragging sensation, tumor mass/compression
GI symptoms, dysuria, increased frequency of urination, pelvic pressure
Resection of a benign tumor is the cure
Malignant: progressive weakness, weight loss, cachexia with seeding into the peritoneum causing massive
ascites
Tumor implants grow on the surface of other structures but do NOT invade
Regional LN can be involved and can metastasize to liver, lung, GIT and the time to the opposite ovary
15% BORDERLINE
Multi-layering with moderate mitosis and nuclear atypia
No stromal invasion
75% 5 year survival
Serous Cystadenoma
No Stromal Invasion
In Either Benign or
Borderline
Psammoma
Bodies
Benign
Borderline
Serous Cystadenocarcinoma
Cystic Component
Nodular Component
10-15% BORDERLINE
70% 10 year survival
5-10% MALIGNANT
Most are unilateral unlike serous
Mutliloculated and solid nodules with increased papillae than benign lesions
35% 10 year survival *better than serous*
Mucinous Cystadenoma
Mucinous Cystadenocarcinoma
Micro:
Resemble endometrial carcinoma but not functional like endometriosis (not
normal endometrium like seen in endometriosis)
Most are malignant and behave like carcinomas due to a mutation in the
PTEN suppressor gene (same as endometrial cancer)
40% are bilateral
4-50% 5 year survival
**Clear Cell Carcinoma variant
Micro:
Occasionally, the nests of cells are cystic and are lined by
columnar mucus-secreting cells
Clinically:
Silent most of the time
Most often benign but there is chance of malignancy
Mostly Unilateral
Brenners Tumor
Tumor
Transitional Epithelium
CA125
Screening Marker for Ovarian Malignancy
High levels seen in the blood of 75-95% of women with
epithelial ovarian cancers
Problems:
Problematic if the tumor is only limited to the ovary, giving
half of them a false negative
Can have increased values in benign lesions and in nonovarian cancers
Mature Teratoma
Mature benign cyst (Dermatoid Cyst)
Seen in young women in active reproductive years
Origin:
Marked differentiation of totipotential germ cells into mature tissues representing all
three germ cell lays (ectoderm, mesoderm, endoderm)
Morphology:
Usually formation of a cyst lined by recognizable epidermis replete with adnexal
appendages: dermoid cyst
Often filled with sebaceous secretion and matted hair that when removed reveal a
hair-bearing epidermal lining
Sometimes there is a nodular projection from which teeth protrude
Occasionally, foci of bone and cartilage, nests of bronchial or GI epithelium and other
recognizable lines of development are also present
Clinically:
90% are unilateral and more often on the right; rarely exceed 10 cm in diameter
For unknown reasons, sometimes can produce infertility
1% have malignant transformation of one of the tissue elements usually taking the form
of squamous cell carcinoma
Prone to undergo torsion, like simple cysts producing an acute surgical emergency
Diagnosis:
Usually incidental on abdominal radiographs or scans because they contain foci of
CALCIFICATION produced by contained teeth
Dermatoid Cyst
Poor Prognostic Factor
Connective Tissue
Neuroepithelium
Epidermis
Hair Follicle
Immature/Malignant Teratoma
Mean age of 18 years old
Morphological:
Often bulky, are predominantly solid or near-solid on transection and are
punctuated here and there by areas of necrosis
One of the cystic foci, although rare, may contain sebaceous secretions, hair
and other features similar to those in the mature teratoma
Micro:
**Distinguishing Feature: variety of immature or barely recognizable areas of
differentiation toward cartilage, bone, muscle, nerve and other structures**
**Ominous are foci of neuroepithelial differentiation because most such
lesions are aggressive and metastasize widely**
Specialized Teratomas
Struma Ovarii is composed entirely of mature
thyroid tissue that may hyperfunction and
produce hyperthyroidism
Appear small, solid, unilateral brown ovarian masses
Struma Ovarii
Dysgerminoma
2% of all ovarian cancers (very rare)
Peak Incidence:
20s-30s and occurs with gonadal dysgenesis
Location:
Mostly Unilateral
Morphology:
Solid, Large to small gray masses
Sheets or cords of large cleared cells separated by scant fibrous
strands
Stroma contain lymphocytes and occasional granuloma
Behavior:
All are malignant but only 33% are aggressive
Treatment:
Cured by surgery and is radiosensitive
Dysgerminoma
Fried Egg
Lymphocytes
Choriocarcinoma (nongestational)
Peak Incidence:
Location:
Unilateral
Morphology:
Identical to placental tumor
Small, hemorrhagic focus with two types of epithelium: cytotrophoblast and
syncytiotrophoblast
Pleomorphism, giant cells and multi-nucleation
Behavior:
Serum Levels:
Secrete Chorionic Gonadotrophin (CGT)/Human Chorionic Gonadotropin (HCG): to be
used as marker
Raised CGT/HCG in the urine and blood
Other rare tumors: Embryonal carcinoma, polyembryoma, mixed germ cell tumor
Choriocarcinoma
Granulosa-Thecal Cell
Peak Incidence:
Location:
Unilateral
Morphology:
Tiny or large
Gray to yellow with cystic spaces
Mixture of cuboidal granulosa cells in cords, sheets or strands and spindle or plump lipid-laden
thecal cells
Granulosal elements may recapitulate ovarian follicle as Call-Exner Bodies
Behavior:
Large amounts of estrogen from the thecal elements and so may promote endometrial or breast
carcinoma, precocious puberty or endometrial hyperplasia
Granulosa element may be malignant, but not theca cells
Thecoma-Fibroma
Peak incidence:
Any age
Location:
Unilateral
Morphology:
Solid gray fibrous cells to yellow, lipid-laden plump thecal cells
Behavior:
Most are hormonally INACTIVE (few elaborate estrogen)
40% will produce ascites and hyrdothorax on right side Meigs Syndrome (Fibroma)
Rarely malignant but sometimes associated with basal cell nevus syndrome
FibroThecoma
Fibrosis
Lipid Laden
Theca Cells
Location:
Unilateral
Morphology:
Usually small, gray to yellow-brown and solid
Recapitulates the cells of testis
Behavior:
Many masculinizing or defeminizing
Defeminizing: Atrophy of breasts, amenorrhea, sterility, loss of hair
Masculinizing: Hirsutism, male distribution of hair, hypertrophy of clitoris,
voice changes
Rarely malignant
Metastasis to Ovary
Peak Incidence:
Older ages
Location:
Mostly bilateral
Morphology:
Solid, gray-white masses as large as 20 cm in diameter
Anaplastic tumor cells, cords, glands, dispersed through fibrous
background
Cells can be signet ring, mucin-secreting (Diffuse Gastric AdenoCa)
From:
GIT tumors, Breast tumors
Krukenberg (bilateral ovarian and Gastric Adenocarcinoma)
Signet Ring Cells
Krukenberg Tumor
Signet Rings
Endometrium
Double Layer of Cells
Vacuolization
Secretory Phase
Possible Symptoms
Amenorrhea (primary or secondary): absence of
menstrual cycle from the beginning or after menarche
Menorrhagia: excessive amount of regular bleeding
(cyclical)
Metrorhagia (Epimenorrhea): irregular non-cyclical
bleeding
Dysmenorrhea:
Primary-onset at menarche; abnormal activity of nerves
and muscles of the cervix
Secondary-onset later in life: endometriosis, leiomyoma
Effects: persistent proliferation and irregular breakdown (DUBdysfunctional uterine bleeding), endometrial hyperplasia,
endometrial carcinoma, breast cancers
Endometriosis
Characterized by the presence of endometrial glands and stroma in a location outside the
endomyometrium
Incidence is high in women with infertility
Clinically:
Dysmenorrhea, menorrhagia, cyclical bleeding from UT, Rectum, Umbilicus, Surgical Scars
Pelvic pain
Pelvic mass filled with degenerating blood (chocolate cyst)
Infertility
Fibrosis -> intestinal obstruction, risk of tubal pregnancy, urinary obstruction
Can regress following pregnancy or after oral contraceptive use
Location:
Frequently multifocal and may involve tissue in the pelvis (ovaries, pouch of Douglas, uterine ligaments,
tubes and rectovaginal septum)
Less frequently in the peritoneal cavity and about the umbilicus
Uncommonly in LN, lungs, heart, skeletal muscle or bone
Laparotomy or Caesarian Scars
Pathogenesis:
Regurgitation theory:
Metaplastic Theory:
Endometrial differentiation of ceolomic epithelium which is the origin of the endometrium itself
Invoked to explain extrapelvic or intranodal implants which cannot be explained in the previous two theories
Endometriosis
Morphology:
Most commonly contains functioning endometrium which undergoes cyclical
bleeding
Because blood collects in these aberrant foci, they usually appear as red-blue
to yellow-brown nodules or implants
Can be anywhere from 1-2 cm in diameter and lie on or just under the affected
serosal surface
Individual lesions can and often coalesce to form large masses
On the ovaries they form large masses called Chocolate Cysts as the blood ages
Consequences:
Seepage and organization occurs leading to fibrosis
Adherence of pelvic structures and sealing of the tubal fimbriated ends ->
Infertility
Distortion of the oviducts and ovaries
Histological Diagnosis:
Required two of the following three:
Endometrial glands, stroma or hemosiderin pigment
Endometritis
Can be part of pelvic inflammatory disease (PID) which has consequences for
the integrity of the fallopian tubes and fertility
May be associated with retained products of conception subsequent to
miscarriage or delivery or a foreign body such as an IUD
Retained products act as a nidus for infection, usually by flora ascending from
the vagina or intestinal tract
Classification:
Acute: Neutrophilic Response
N. gonorrhea and C. trachomatis are likely culprits
Histologically: neutrophilic infiltrate in the superficial endometrium and glands co-exist
with stromal lymphoplasmacytic infiltrate
Postpartum: puerpural sepsis leading to offensive lochia (foul smelling discharge)
Pyometrum obstruction leading to neoplasm or fibrosis
Clinically:
All forms may present with fever, abdominal pain, menstrual abnormalities,
infertility and ectopic pregnancy due to damage to the fallopian tubes
Endometrial Hyperplasia
Ranges from:
Simple Cystic Hyperplasia
Complex Hyperplasia
Complex Atypical Hyperplasia
With enough time, the hyperplasia may become autonomously proliferating and no longer
needs the strong estrogen influence (not good because high malignant potential)
Risk of developing carcinoma is based on the level of atypia and the severity of the
hyperplastic change
Diagnosis/Treatment:
Look for source of estrogen
Biopsy tissue to see for transformation
Balance with progesterone or correct underlying condition
Endometrial Hyperplasia
Simple Cystic
Complex
Endometrial Polyp
Occurs around menopause (perimenopausal)
Morphology:
Ranges from 0.5-3 cm in diameter, usually sessile and hemispheric
Large enough lesions can protrude into the uterine cavity
Histologically:
Composed of endometrium resembling the basalis, frequently with small
muscular arteries
Some have normal endometrial architecture but more often they have
cystically dilated glands
Stromal cells are monoclonal and have a cytogenic rearrangement making it
clear it is neoplastic
Endometrial Carcinoma
Epidemiology:
55-65 years old
Perimenopausal women with estrogen excess: endometroid histology
Older women with endometrial atrophy: serous carcinoma histology
Risk Factors:
Pathogenesis:
Second most common cancer associated with HNPCC (mismatch repair)
Sporadic cases have a high frequency of inactivation of these genes by methylation of the promoter and as
a consequence have a relatively unstable genome (MSI)
Mutations in PTEN tumor suppressor gene (rare in Serous Type but p53 is evident)
Clinically:
Marked Leukorrhea (thick, whitish-yellowish vaginal discharge) and irregular bleeding and in
postmenopausal women this signifies erosion and ulceration of the endometrial surfaces
With time, palpable enlargement and it will become fixed to surrounding structures by extension of the
cancer beyond the uterus
Endometroid Carcinoma:
**Synchronous endometroid tumor: two separate primary neoplasms is not stage III, are both Stage I and
has favorable prognosis
Serous Carcinoma:
Metastases:
Endometrial Carcinoma
Exophytic
Serous Carcinoma
Severe Atypia
Morphology:
Large, fleshy mass with hemorrhage and necrosis
Composition:
Epithelial and mesenchymal cells (leio, rhabdo,
chondro, osteo)
Leiomyoma
Large neoplasms may develop foci of ischemic necrosis with areas of hemorrhage and cystic softening and after
menopause they may become densely collagenous and even CALCIFIED
May develop attenuated stacks an even become attached to the surrounded organs from which they develop a
blood supply and then free themselves from the uterus to become a parasitic leiomyoma
Clinically:
Asymptomatic
Menorrhagia, with or without metrorrhagia
Large masses: dragging sensation
Acutely, pain, red degeneration (necrosis) especially in pregnancy
No malignant potential
Treatment:
Laparoscopic resection or hysterectomy, myomectomy
Leiomyosarcoma
Typically arise de novo from the mesenchymal cells of the myometrium, NOT a preexisting leiomyoma
Morphology:
Almost always single in contradiction to frequently multiple leiomyoma
Grossly:
Histology:
Closely resembling leiomyomas
Wildly anaplastic tumor
Because it is difficult to differentiate some, they are termed smooth muscle tumors of uncertain
malignant potential
Diagnosis:
Tumor Necrosis, cytologic atypia, mitotic activity (need all three)
Poor Prognosis because recurrence after removal is common and high level of
metastases typically to the lungs
40% 5 yr survival rate
Anaplastic lesions have a poorer prognosis than the better differentiated tumors
Cervix
Ectocervix: lined by hormonally responsive
stratified squamous epithelium (nonkeratinized);
post puberty, mature cells store glycogen which
supports the growth of normal flora
Endocervix: lined by simple columnar epithelium;
endocervical glands are crypt-like spaced lined by
the same epithelium
Squamo-Columnar Junction: initially at the
external cerival os
Cervicitis
Acute
Typically in the endocervix (not erosion)
Organisms: Gonococcal, Chalmydia, Candida, Trichomonas, Herpes, one or
more types of HPV
Can be post-partum or post dilation and curettage (procedure in which
material inside the uterus is removed)
Causes purulent vaginal discharge
Chronic
Non-specific, usually incidental
Inflammatory infiltrate consists of lymphocytes and plasma cells normally
present in the wall of the cervix
Granularity and thickening occurs as a result of fibrosis
As the overgrowth of the regenerating squamous epithelium blocks the orifices
of endocervical glands in the transformation zone, it produced retention
(nabothian) cysts that are lined by columnar mucus secreting epithelium
Transformation
Zone Metaplasia
Normal
Endocervix
Endocervical Polyp
Etiology:
Pre-menopausal women
Morphology:
Can be as large as a few cm, are soft and yielding to palpation
Smooth glistening surface with underlying, cystically dilated spaces
filled with mucinous secretion
Histology:
Surface epithelium and lining of the underlying cysts are composed of
the same mucus-secreting columnar calls
Complications:
Superimposed chronic inflammation may lead to squamous
metaplasia of the covering epithelium and ulcerations
May bleed and thus cause some concern but NO malignant potential
Condyloma Acuminatum
Condylomas: Anogenital Warts and In the moist environment of the Vulva
they tend to be large
2 forms exist: Condyloma lata (secondary syphilis) and acuminatum
Condyloma acuminatum
Loss of Maturation:
Sequence from bottom to top is lost beginning at the basal
layer and progressing until the entire thickness of the
epithelium is involved
Nuclei remain large and the cells remain cuboidal
Mitoses appear above the basement membrane
Glycogen is not stored
Squamous intraepithelial lesion (SIL): can be split into two categories, low grade (CIN I) or
high grade (CIN II, III)
Risk Factors for the development of CIN and this Invasive Ca:
Diagnosis:
HPV can be diagnosed by molecular methods like FISH
Most important is to do routine PAP smears
PAP smears:
CIN
Normal
CIN II
CIN I
CIN III
PAP Smear
Course:
If the cancer extends into the parametrial soft tissue, it can fix the uterus to the pelvic
structures
Size of the lesions will determine the likelihood of spread to LN (bigger = more spread)
Distant metastases will occur much later and can involve: para-aortic nodes, remote
organ involvement, invasion of adjacent structures like bladder or rectum
Symptoms:
Leukorrhea, unexpected vaginal bleeding, painful coitus (dyspareunia), dysuria
Pyometron: obstruction of the cervix
Stage 0: 100%
Stage 1: 90%
Stage 2: 82%
Stage 3: 35%
Stage 4: 10%
Cryo-surgery
Electrocoagulation
Laser
Cone biopsy: including total squamocolumnar junction
Chemotherapy can increase survival in cancer patients
Carcinoma
Keratin Pearls
Genital Herpes
Syncytial
Cells
Vaginal Adenosis
Occurs in girls (around 10 years) whose mother received
DES during pregnancy to prevent morning sickness
Characterized by endocervical type glands in the vaginal
wall
Pathogenesis:
Thought to be the inhibition of transformation of Mullerian
epithelium into squamous epithelium
Consequences:
Some girls can develop clear cell adenocarcinoma from age 1035
Morphology:
Appear as red granular foci and are lined by mucus-secreting or
ciliated columnar cells
Sarcoma Botryoides
Embryonal Rhabdomyosarcoma
Etiology:
Encountered in infants and children younger than age
5
Morphology:
Produces soft, polypoid masses
Appears like a bunch of grapes hanging in the vagina
Vulva
Normal:
Consists of the majora, minora, vestibule and clitoris
Bartholin glands open into the vaginal introitus for
lubrication
Skenes glands around the uruthral opening
(homologous to the prostate glands in the male)
Pathology:
Bartholinitis:
Acute inflammation of the inferior part of the labium major
Can cause abscess formation
Associated with strep, staph, gonococci, and E. coli
Vulvitis
Moist hair-bearing skin and delicate membrane of the vulva
are vulnerable to many non-specific microbe-induced
inflammations and dermatologic disorders
Intense itching and subsequent scratching often only
exacerbates the primary condition
Five most important infectious agents in NA:
HPV -> condyloma acuminata and vulvar intraepithelial
neoplasia
Condyloma Latum -> plaque like papule of secondary syphilis
In postmenopausal women
Thinning of the epidermis and disappearance of the rete pegs, hydropic degeneration of
the basal cells, superficial hyperketosis, dermal fibrosis with a scant perivascular,
mononuclear infiltrate
Smooth, white plaques papules that with time can coalesce (parchment like) with dense
collagen
Very Low to NO malignant potential
High Levels of T cells and high association with other autoimmune diseases suggests
that it is Autoimmune in nature
Appears as leukoplakia
Pre-neoplastic lesion
Can appear as a reddish brown plaque
Needs surgical excision so that it doesnt
progress to carcinoma
Carcinoma Vulva
Usually occurs in women over 60 years old
Appears as a plaque, nodule or ulcerous lesion
Typically occurs on the anterior 2/3 of the labia
majora
Usually of the squamous cell variety
Spreads to the inguinal and pelvic nodes
Invasive Squamous cell carcinoma is ulcerated
with raised edges or can be a fungating tumor
mass
Histology:
Large epitheloid cells infiltrate the epithelium, singly and in groups, with
abundant granular cytoplasm and occasional cytoplasmic vacuoles containing
mucin that stain positive with PAS
When the cells are confined to the epithelium, they may persist for years
or even decades without evidence of invasion
When associated with an appendageal tumor, the cells extend into the
skin appendages and invade locally with ultimate metastases to more
distant sites (usually within the first 2-5 years)
Normal Placenta
Placental villi surrounded by maternal blood
Embryonic vessel contains nucleated red cells
Surrounded by loose mesenchyme
Covered by cytotrophoblasts and
syncitiotrophoblasts
Loose Mesenchyme
Nucleated
Fetal Blood
Ectopic Pregnancy
Implantation of the fertilized ovum in any site other than the
normal uterine location (about 1% of pregnancies)
90% of ectopic pregnancies are in the oviducts (tubal
pregnancy)
Other sites are the ovaries, abdominal cavity, intrauterine portion
of the oviducts (interstitial pregnancy)
Pathogenesis:
Any factor that retards passage of the ovum along its course
through the oviducts to the uterus predisposes to an ectopic
pregnancy
In half of the cases, the obstruction is base on chronic
inflammatory changes in the oviduct, although tumors and
endometriosis can also cause an obstruction
Morphology:
All are characterized by fairly normal early development of the
embryo with the formation of placental tissue, the amniotic sac
and decidual changes
Abdominal pregnancies are often carried to term
Ectopic Pregnancy
Tubal Pregnancy and Rupture:
Increased risk with PID and tubal adhesions or endometriosis with fibrosis (50% are
idiopathic)
There is lack of space, poor vasculature and limited placental size and will usually
rupture 2-6 weeks after fertilization
The invading placenta eventually burrows through the wall of the oviduct causing
intratubal hematoma (hematosalpinx), intraperitoneal hemorrhage, or both
The tube distends by the contained mass of freshly clotted blood in which may be seen
bits of gray placental tissue and fetal parts
Curettings will show NO Chorionic Villi; will have secretory glands
**Rule out Spontaneous Abortion if Chorionic Villi**
Clinically:
Until rupture, an ectopic pregnancy will appear normal with cessation of menstruation
and elevation of serum and urinary placental hormones
Under the influence of these hormones, the endometrium undergoes the characteristic
hypersecretory and decidual changes
Upon rupture, there may be a sudden onset of intense abdominal pain and signs of an
acute abdomen followed by shock where prompt surgical intervention is necessary
If right sided, will mimic acute appendicitis
Lab values of HCG will be elevated as they would be in normal pregnancy, but upon
rupture, the values will quickly decline which will eventually lead to the degeneration
of the corpus luteum which leads to a decrease in estrogen and progesterone
The lack of hormones will lead to the breakdown of the endometrium -> bleeding
Ectopic Pregnancy
Abortion
Defined as delivery of the embryo from week 8 or the
fetus up to 20 weeks (anything from 20-40 weeks is
termed pre-mature delivery)
Usually caused by defective chromosomes
Symptoms:
Vaginal bleeding which is rapid and severe which can lead
to shock
Lower abdominal pain due to uterine contraction
Diagnosis:
Demonstrate chorionic villi or embryo
*In ruptured ectopic pregnancy -> no demonstrable
chorionic villi*
Placental Abnormalities
Placenta Previa:
The placenta implants over the internal os which leads to ante
partum hemorrhage
Diagnosed via ultrasound and requires caesarian section
Abruptio placenta:
Premature separation of the placenta which leads to ante
partum hemorrhage, shock, DIC, premature labor or fetal death
Placenta accreta:
Absence of plane of separation between the villi and
myometrium which leads to severe POST partum hemorrhage
Deep implantation of the placenta into the myometrium
Requires hysterectomy or can lead to maternal death
Pre-eclampsia/Eclampsia
Gestational Edema with proteinuria and hypertension GEPH with GE, P, H
occurring in the 3rd trimester (distinct from a hypertensive woman becoming
pregnant)
Occurs in 5% of pregnancies and 10% of PE patients develop seizures (eclampsia)
Solutions are to induce labor or a caesarian section
Problems disappear after birth of the baby
Risk Factors:
Pathology:
The basic feature underlying all cases is inadequate maternal blood flow to the
placenta, secondary to inadequate development of the spiral arteries of the placental
bed
In the 3rd trimester, the musculoelastic walls of the spiral arteries are replaced by a
fibrinous material, permitting them to dilate into wide vascular sinusoids but in preeclampsia and eclampsia, the walls are retained and the channels remain narrow
Can cause placental ischemia through the possible mechanism of an autoimmune
reaction to the placenta
Pre-eclampsia/Eclampsia
Consequences:
Placental hypoperfusion with an increased predisposition to the development of
infarcts
Reduced elaboration by the trophoblast of the vasodilators prostacyclin, prostaglandin
E2 and NO which normally oppose the effects of rennin and angiotensin, which leads
to the hypertension
Production of the ischemic placenta of thromboplastic substances such as tissue factor
and thromboxane which are the cause for the DIC
Acute atherosis of the spiral arteries: foamy macrophages in necrotic vessel walls which
is characteristic and later on macrophages and lymphocytes
Multiorgan changes
Kidneys:
Depends on the severity of the DIC
Changes consist of fibrin thrombi within the glomerular capillaries, accompanied by endothelial
swelling and possibly mesangial hyperplasia
Focal glomerulitis may ensue and when enough are affected, the blood flow to the cortex is reduced,
possible resulting in renal cortical necrosis that may be bilateral and fatal
Other organs:
Microvascular thrombi can occur in brain, pituitary, heart and elsewhere which have the potential for
producing focal ischemic lesions accompanied by microhemorrhages
Liver:
Periportal hypertension
Hydatidiform Mole
Partial:
1:2000 pregnancies in the US and West (higher in Asian countries)
Compatible with early embryo formation and therefore contains fetal parts, has some normal chorionic
villi and is almost always triploid (69, XXY = 23X sperm and 23Y sperm plus 23X egg)
Normal egg is fertilized by two spermatozoa/diploid sperm resulting in a triploid karyotype with a
preponderance of paternal genes
Hydatidiform Mole
Complete
Partial
Karyotype
69,XXY: Triploidy
Villous Edema
All Villi
Some Villi
Trophoblast Prolif
Diffuse/Circum.
Focal/Slight
Atypia
Often
Absent
Serum hCG
Elevated
Less Elevated
hCG in tissue
++++
Behavior
2% Chorio Ca
Rare Chorio Ca
Gestational Choriocarcinoma
Pathology:
Friable, hemorrhagic mass with extensive infiltration and metastases in the lung, brain and
liver
Cells are malignant cytotrophoblasts and syncitiotrophoblasts
Causes hemorrhage and necrosis (bloody discharge per vagina)
NO CHORIONIC VILLI
hCG is elevated but in order to confirm diagnosis, must biopsy
Gestational Choriocarcinoma
Rare
Proliferation of the cytotrophoblasts in uterus
Follows an abortion or normal pregnancy
No villi, no fetal parts, no
syncitiotrophoblasts
Cells have placental lactogen but very little
hCG
Cured by curattage