I.
Bladder
a.
Urothelial (Transitional) Cell
Carcinoma
b.
Papilloma
c.
Mesenchymyal Tumors of the Bladder
II.
Testis
a.
Germ Cell Tumors
i.
Seminoma
ii.
Non-seminomatous (NSGCT)
1.
Teratoma
2.
Yolk-sac tumor
3.
Embryonal carcinoma
4.
Choriocarcinoma
5.
Intratubular germ cell neoplasia (IGCN)
III.
Prostate
a.
Benign Prostatic Hyperplasia (BPH)
b.
Prostate Cancer
IV.
Ovary
a.
Inflammatory Disorders
i.
Tubo-ovarian abscess (PID)
ii.
Other Infectious Oophoritis
iii.
Autoimmune Oophoritis
b.
Endometriosis
c.
Functional Cysts
i.
Follicular Cysts
ii.
Luteal Cysts
d.
Polycystic Ovarian Disease
e.
Ovarian Tumors
i.
Epithelial (Stromal) Tumors
1.
Serous Tumors
2.
Mucinous Tumors
3.
Endometrioid Tumors
4.
Clear Cell Tumors
5.
Transitional (Brenner) Tumors
ii.
Germ Cell Tumors
iii.
Sex-Cord Tumors
1.
Granulasa-Theca Cell Tumors
2.
Fibrothecoma and Fibromas
3.
Sertoli-Leydig Cell Tumors
iv.
Metastasis Tumors
V.
Fallopian Tube
a.
Salpingitis
b.
Ectopic Pregnancy
c.
Paratubal cyst
d.
Adenomatoid Tumor
e.
Adenocarcinoma
VI.
Uterus
a.
Non-neoplastic (Endometrial)
i.
Anovulatory Cycle
ii.
Luteal Phase Defect
iii.
Endometritis
iv.
Polyps
v.
Adenomyosis
b.
Neoplastic (Endometrial)
i.
Endometrial Hyperplasia
ii.
Adenocarcinoma
1.
Endometrioid Carcinoma
2.
Serous Carcinoma
iii.
Malignant Mixed Mullerian Tumor (MMMT)
iv.
Endometrial Stromal Tumors
c.
Neoplastic (Myometrial)
i.
Leiomyoma
ii.
Leiomyosarcoma
d.
Gestational Trophoblastic Disease (GTD)
i.
Hyatidiform Mole
ii.
Choriocarcinoma
VII.
Cervix (part of the uterus)
a.
Non-Neoplastic Diseases
i.
Cervicitis
ii.
Endocervical Polyps
b.
Neoplastic Diseases
i.
Condyloma Acuminatum
ii.
Cervical Intraepithelial Neoplasia (CIN)
iii.
Squamous Cell Carcinoma
iv.
Adenocarcinoma
v.
Clear Cell Carcinoma
VIII.
Vagina
a.
Non-Neoplastic Diseases
b.
Neoplastic Diseases
i.
Benign Tumors
ii.
Vaginal Intraepithelial Neoplasia (VAIN)
iii.
Squamous Cell Carcinoma
iv.
Adenocarcinoma
v.
Embryonal Rhabdomyosarcoma
(sarcoma botryoides)
IX.
Vulva
a.
Non-Neoplastic Diseases
i.
Bartholin gland cysts
ii.
Vestibulitis
iii.
Leukoplakia
1.
Inflammatory Dermatoses
a.
Lichen Sclerosus
b.
Squamous Hyperplasia (Dystrophy)
b.
Neoplastic Diseases
i.
Papillary Hidradenoma
ii.
Condyloma Acuminatum
iii.
Vulvar Intraepithelial Neoplasia
Squamous Cell Carcinoma
iv.
Extramammary Paget’s disease
v.
Melanoma
I.
Bladder
|
Low Grade |
High Grade |
|
Polarity maintained |
Loss of polarity |
|
Cells not crowded |
Cellular crowding |
|
Minimaly
nuclear atypia |
Nuclear atypia |
|
Rare (basilar) mitoses |
Increased mitoses |
|
Treatment: resection only Larger, higher grade: - transurethral resection - intravesical
chemotherapy (in bladder) |
Treatment: radical cystectomy/cystoprostatectomy |
a.
Urothelial (Transitional) Cell
Carcinoma
90% of all bladder neoplasms
50-80 yo, M:F=3:1
Risk factors: smoking, occupational (2-naphthlamine), cyclophosphamide,
Symptoms: hematuria
Diagnosis: cystoscopy with
biopsy/transurethral resection
b.
Papilloma
benign
(covered with normal urothelium): not the same as
carcinoma in situ
rare
(1% of epithelial bladder tumors)
c.
Mesenchymyal Tumors of the Bladder
pediatric;
most common: rhabdomyosarcoma (small round blue
cells)
adults: leiomyosarcoma
II.
Testis
a.
Germ Cell Tumors
most common testicular tumor
(95%)
symptoms:
painless testicular masss
spread:
retroperitoneal lymphatics
epidemiology:
Caucasian, cryptorchidism (intra-abdominal), familial (chromosome
12)
-
0-4yo (yolk sac, teratoma)
- 15-35yo (testicular tumors are most common type of malignant
neoplasm for this age range)
Treatment:
orchectomy and:
|
|
Chemosensitive |
Radiosensitive |
|
Seminoma |
Yes |
Yes |
|
Non-seminomatous |
Yes |
No |
i.
Seminoma
often pure, lobulated,
fleshy pink-gray; confined to testis, Wilm’s-like
histology:
solid sheets, clear cytoplasm, prominent nucleoli (“fried egg” cell pattern)
ii.
Non-seminomatous (NSGCT)
usually
not pure, hemorrhagic
1.
Teratoma
except
for rare dermoid cyst subtype, has poor prognosis (worse than ovarian teratoma)
tan
gray, cystic
occurs in
pure form in childhood
2.
Yolk-sac tumor
has metastatic potential
marker: AFP (marks epithelial,
but not stromal)
gross:
yellow
3.
Embryonal carcinoma
4.
Choriocarcinoma
5.
Intratubular germ cell neoplasia (IGCN)
tumor
marker: PLAP (placental alkaline phosphatase)
III.
Prostate
a.
Benign Prostatic Hyperplasia (BPH)
extremely
common (increases with age)
etiology:
serum testosterone drop (estrogen conversion in peripheral tissues) à
increased androgen receptos
location: periourethral transition zone (TZ) (may not be palpable on digital rectal
exam)
may à urinary obstruction (incomplete
voiding, hesitancy dribbling à bladder musculature
hypertrophy, renal failure)
treatment:
transurethral resection of prostate (TURP)
BPH is not a precursor for cancer
b.
Prostate Cancer
second most common cancer in males (1st:
skin)
second
leading cause of cancer death in males (1st: lung)
tendency to
die “with” rather than “from”
Gleason grading system:
well-differentiated à poorly differentiated (primary+secondary score: 1 through 5 + 1 through 5)
location:
60-80% are in peripheral zone (PZ) = PIN (prostatic
intraepithelial neoplasia)
diagnosis: transrectal biopsy after suspicious DRE and/or elevated PSA
spread: perineural invasion, lymphatic (pelvic)
à
bone (osteoblastic mets)
IV.
Ovary
a.
Inflammatory Disorders
rare;
associated with infertility
i.
Tubo-ovarian abscess (PID)
ii.
Other Infectious Oophoritis
iii.
Autoimmune Oophoritis
b.
Endometriosis
= presence of endometrial
tissue (responsive to hormonal cycle) in sites other than uterus
hemorrhagic “chocolate” cysts à
adhesions
histology:
(2 of the following 3) 1) endometrial glands; 2) endometrial stroma; 3) hemosiderin pigment
sites
(decreasing frequency): ovaries,
uterine ligaments, rectovaginal septum,
peritoneum...umbilicus, vagina vulva, GI, pleura
epidemiology:
reproductive age, infertility, pelvic pain, abnormal bleeding, dysmenorrheal
theories of
pathogenesis: 1) regurgitation; 2) metaplasia; 3) lymphovascular dissemination
c.
Functional Cysts
i.
Follicular Cysts
usually multiple (unruptured
graafian follicles, sealed rupture follicles)
clear serous fluid
ii.
Luteal Cysts
enlarged
corpus luteum
distinct
bright yellowàorange lining (composed of luteinized
granulose cells)
d.
Polycystic Ovarian Disease (PCOD)
bilateral
ovarian enlargement
associated:
obesity, hursuitusm, virilism,
oligomenorrhea
appearance
enlarged ovaries, numerous cystic follicles, fibrous cortical thickening
may à endometrial hyperplasia, carcinoma
(unopposed estrogen stimulation)
e.
Ovarian Tumors
80% are benign
third
most common gynecological cancer
risk
factors, BRCA1, BRCA2,
older age, nulliparity, gonadal dysgenesis
oral
contraceptives have a protective effect
symptoms:
pain, increasing girth, ascites, vaginal bleeding
most
common metastatic primary sites: opposite ovary, endometrium, colon, pancreas, stomach,
breast
bilateral metastatic tumor to ovaries from GI origin: Krukenberg tumor (signet ring cells)
i.
Surface Epithelial (Stromal) Tumors
most common benign and malignant
ovarian tumor
spread:
penetrating ovarian capsule à peritoneal surface spread, lymphatic à
lungs, pleura, liver
marker:
CA-125
1.
Serous Tumors
most common epithelial tumor
(most: benign)
often
bilateral, unilocular
benign:
simple; malignant: complex (papillary, solid areas, necrosis)
2.
Mucinous Tumors
most:
benign (rarely bilateral)
multilocular
two
subtypes: gastriointestinal (pseudomyxoma
peritonei), endocervical
3.
Endometrioid Tumors
most:
malignant (frequently bilateral)
association:
endometriosis, synchronous
endometrial carcinoma (15-30%)
4.
Clear Cell Tumors
malignant,
highly aggressive
5.
Transitional (Brenner) Tumors
most:
benign, adenofibromatous
ii.
Germ Cell Tumors
second
most common ovarian tumor
usually in
pure form (unlike in testes)
1.
Teratoma
most
common GCT in ovary
cystic, ectodermal (hair, teeth, bone = dermoid cyst)
rarely of
just one tissue type (if so, most commonly: thyroid = struma
ovarii (if functionalàhyperthyroidism),
neuroendocrine = carcinoid)
2.
Dysgerminoma
“seminoma” of the ovary
3.
Yolk Sac
4.
Choriocarcinoma
iii.
Sex-Cord Tumors
least common ovarian tumor
arise
from stromal (fibroblasts, smooth muscle cells)
1.
Granulosa-Theca Cell Tumors
post-menopausal,
unilateral, “coffee bean nuclei”
2.
Fibrothecoma and Fibromas
common in
patients with Basal-Cell
Nevus Syndrome
association
with ascites and right sided pleural effusion (Meig’s syndrome)
3.
Sertoli-Leydig Cell Tumors
may
produce androgens (analogous to testicular form)
iv.
Metastasis Tumors
V.
Fallopian Tube
a.
Salpingitis
inflammation
(component of PID)
b.
Ectopic Pregnancy
fallopian
tube: most common site
usually à
hemorrhage, rupture
(peritoneal cavity) à shock
potential
medical emergency
c.
Paratubal cyst
small, unilocular
very
common
Hydatid
cyst of Morgagni: large mullerian
duct remnant cyst
d.
Adenomatoid Tumor
ß mesothelium (benign)
e.
Adenocarcinoma
rare
(more commonly: secondarily involved)
VI.
Uterus (body)
normal
uterus: cervix, intermediate zone, body (corpus)
body:
myometrium, endometrium
formed
from fusion of mullerian ducts
classic
manifestation of uterine disease: “abnormal uterine bleeding”
- menorrhagia:
excessive bleeding during menses
- metrorrhagia: bleeding between
menses
- menometrorrhagia:
(both)
functional
disorders account for majority = dysfunctional uterine bleeding (DUB)
a.
Non-neoplastic (Endometrial)
i.
Anovulatory Cycle
most common cause of DUB
lack of
ovulationà “unopposed”
estrogen stimulation
(with
ovulation, progesterone is produced by ovary)
if
chronic à endometrial hyperplasia
ii.
Luteal Phase Defect
iii.
Endometritis
usually
bacterial
may be
acute (uncommon) or chronic (associated with PID)
signs
and symptoms (chronic); abnormal bleeding, pain, discharge, infertility
biopsy:
plasma cells, etc.
iv.
Polyps
non-neoplastic;
posterior wall of the uterine cavity
estrogen-responsive;
may à
abnormal bleeding
v.
Adenomyosis
endometrial glands and stroma within myometrium
diffuse
uterine enlargement
not
always symptomatic
b.
Neoplastic (Endometrial)
i.
Endometrial Hyperplasia
increased gland:stromal ratio
related to
prolonged exposure to estrogen in absence of progesterone
(conditions
with increased estrogen: anovulatory
cycles, obesity, PCOD, granulosa cell tumors, tamoxifen therapy)
perimenopausal women
atypical
hyperplasia: precursor for endometrioid adenocarcinoma
ii.
Adenocarcinoma
1.
Endometrioid Carcinoma
most common gynecological cancer
risk
factors: obesity, diabetes, hypertension, infertility
decreased
incidence among smokers
pathogenesis:
unopposed estrogen stimulation à hyperplasia
(is
the reason why birth control/hormone replacement includes progesterone)
spread:
myometrium invasion à pelvis (direct
continuity)
2.
Serous Carcinoma
less
common; not associated with hyperestrinism or
hyperplasia
similar/identical to
ovarian serous tumors
p53
mutations;
iii.
Malignant Mixed Mullerian Tumor (MMMT)
highly
aggressive (epithelial and mesenchymal)
= carcinosarcoma
may
show differentiation toward native or non-native uterine elements
iv.
Endometrial Stromal Tumors
1.
stromal
nodule (benign)
2.
stromal
sarcoma (malignant)
c.
Neoplastic (Myometrial)
i.
Leiomyoma
benign
tumors of smooth muscle (does not à malignant)
common
(30% of menstruating women over 30); often multiple
can be
serosal, submucosal (form
which à
infertility), intramural
characteristic
“whorled” appearnace
ii.
Leiomyosarcoma
often solitary; larger than benign, hemorrhagic, necrotic,
mitotic figures
may be
STUMP (smooth muscle tumors of uncertain malignant potential)
d.
Gestational Trophoblastic Disease (GTD)
extremes of
reproductive age
epidemiology:
i.
Hyatidiform Mole
molar pregnancy
complete mole: no maternal chromosomes, no embryonic
development, 90% are 46XX
partial mole: usually triploid (69XXY); rarely: tetraploid (92XXXY); fertilization of egg by two sperm;
embryo may develop
pathology: edematous villi
(“clusters of grapes”)
ii.
Choriocarcinoma
rare,
malignant, derived from syncytio- and cytotrophoblasts during pregnancy
no villi; often presents with metastases to lung, vagina,
bone, brain
aggressive,
but high rate of cure: chemotherapy
VII.
Cervix (part of the uterus)
squamocolumnar junction: transition from
squamous epithelium to columnar external cervical os
a.
Non-Neoplastic Diseases
i.
Cervicitis
1.
chronic cervicitis
results
from proliferation of squamous mucosa à
obstruction of glandular crypt openings
essentially universal in reproductive
age women; asymptomatic
2.
acute cervicitis
etiologic
agents: chlamydia, gonococcus, mycoplasm,
Herpes Virus 2, trichomonas, candida
ii.
Endocervical Polyps
non-neoplastic
proliferation of fibrous stroma
b.
Neoplastic Diseases
i.
Condyloma Acuminatum
= venereal wart
sexually
transmitted (HPV 6,11)
condylomas are not considered pre-malignant
ii.
Cervical Intraepithelial Neoplasia (CIN)
(HPV 16,18: E6, E7 à RB)
PAP smear screens for this
risk
factors: number of partners, age of sexual initiation, promiscuity of male partner,
smoking
arise at
squamocolumnar junction
(lowest
grade: indistinguishable histologically from condyloma; majority of low grade lesions regress)
CIN I, CIN II, CIN III
(related to epithelial thickness)
iii.
Squamous Cell Carcinoma
second
most common cancer in women world-wide (1st: skin cancer)
risk
factors: same as for CIN
spread by
local extension
most
deaths are from complications of local extension (e.g. urinary obstruction)
iv.
Adenocarcinoma
increasing in
incidence; also related to HPV
(18)
v.
Clear Cell Carcinoma
most
occur in women exposed in utero to DES
median
age: 19; survival: 90%
VIII.
Vagina
a.
Non-Neoplastic Diseases
rare;
Gartner’s duct cysts (Wolffian duct), mucous cysts,
endometriosis
b.
Neoplastic Diseases
i.
Benign Tumors
leiomyoma, hemangioma, rhabdomyoma, non-neoplastic stromal
polyps
ii.
Vaginal Intraepithelial Neoplasia (VAIN)
HPV-related
iii.
Squamous Cell Carcinoma
rare,
HPV-related
iv.
Adenocarcinoma
v.
Embryonal Rhabdomyosarcoma
(sarcoma botryoides)
IX.
Vulva
histology: identical to skin
a.
Non-Neoplastic Diseases
i.
Bartholin gland cysts
result
from obstruction of Bartholin duct (prior infection)
ii.
Vestibulitis
inflammation of
glands at posterior introitus
iii.
Leukoplakia
1.
Inflammatory Dermatoses
a.
Lichen Sclerosus
postmenopausal
pale,
parchment-like areas of skin
b.
Squamous Hyperplasia (hyperplastic dystrophy)
2.
Neoplastic diseases
VIN, SCC, Paget’s
b.
Neoplastic Diseases
i.
Papillary Hidradenoma
benign
arise
from modified apocrine sweat glands
ii.
Condyloma Acuminatum
see
above
iii.
Vulvar Intraepithelial Neoplasia (VIN)
related to
HPV infection; associated with synchronous squamous
neoplasm of cervix or vagina
iv.
Squamous Cell Carcinoma
HPV 16, 18
risk
factors: lichen sclerosis, squamous hyperplasia
v.
extramammary Paget’s disease
analogous to
Paget’s disease of the breast
unlike
Paget’s disease of the nipple, is usually confined to epidermis
vi.
Melanoma