3. VULVA
• Synonymous with EXTERNAL genitalia
• Everything ANTERIOR to the INTROITUS
• Usual classification of Degen., Inflam.,
Neopl.
• Common Diseases:
– BARTHOLIN Cyst
– Vulvar Vestibulitis
– Deg./Inflam. Epithelial: LICHEN diseases
– BENIGN tumors: Condyloma(ta)
– MALIGNANT tumors: VIN, SCC
4. Result from
Inflammation/Obstruction
of the Bartholin glands
(i.e., greater vestibular
glands)
Often result in abscesses
Surgical removal is
curative when local
procedures are
inadequate or often
recurrent
NEVER become
malignant
20. • 90%
VAGINITIS
• Bacterial Vaginitis is the most common cause of vaginitis,
•
•
accounting for 50% of vaginitis cases. As previously mentioned, BV is
caused by an overgrowth of organisms such as Gardnerella vaginalis
(gram-variable coccobacillus), Mobiluncus species, Mycoplasma
hominis, and Peptostreptococcus species. Risk factors include
pregnancy, intrauterine device (IUD) use, and frequent douching.
Candida species (C albicans, C tropicalis, and C glabrata) are
airborne fungi that are natural inhabitants of the vagina in as many as
50% of women, and vaginal candidiasis is the second most common
cause of vaginitis. Risk factors include oral contraceptive use, IUD use,
young age at first intercourse, increased frequency of intercourse,
receptive cunnilingus, diabetes, HIV or other immunocompromised
states, chronic antibiotic use, and pregnancy.
T. vaginalis infection, the third most common cause of vaginitis, is
caused by trichomonads. These organisms are flagellated protozoans.
Trichomonads primarily infect vaginal epithelium, and they less
commonly infect the endocervix, urethra, and Bartholin and Skene
glands. Trichomonads are transmitted sexually and can be identified in
as many as 80% of male partners of infected women. Risk factors
include tobacco use, unprotected intercourse with multiple sexual
partners, and the use of an IUD.
48. ENDOMETRIOSIS
Defined as normal endometrial glands OUTSIDE
the confines of the myometrium
Reverse menstruation vs. Embryologic “rest”
theories
EXTREMELY common cause of cyclical
abdominal/pelvic pain
Broad Ligament, Ovary (“chocolate cysts”),
Peritoneum, Bowel, Umbilicus
92. OVARIAN TUMORS
•
•
•
•
Solid vs. Cystic
Functional vs. NON-functional
Benign vs. Malignant
First clinical presentation may be ascites,
in carcinomas.
• Malignant ascites in a woman is ovarian
cancer until proven otherwise
• CA-125 is THE important tumor marker in
ovarian cancer, especially as a follow up.
101. “GERM CELL” Tumors
• Teratomas (usually benign in ovary), i.e.,
“mature” cystic teratoma or dermoid cyst
• “Immature” teratomas are regarded as
malignant
• Dysgerminoma (look exactly like the
testicular seminoma), malignant
• Endodermal Sinus (Yolk Sac),
malignant, Just like testicular
• Choriocarcinoma, malignant, just like
testicular
116. Ectopic Pregnancy
• Chiefly TUBAL, but ovarian or
abdominal rare
• 1% OF NORMAL WOMEN
• 35%-50% OF WOMEN with
previous SALPINGITIS/PID
• + HCG, Abdominal pain, 1st
trimester, ultrasound
127. TOXEMIA of PREGNANCY
(PRE-eclampsia)
• Hypertension
• Proteinuria
• Edema
• Related to Placental Ischemia, but MANY
theories
• Risk for DIC, convulsions (eclampsia)
129. Placental Infections
• Villitis vs. chorionamnionitis vs. funisitis
• ASCENDING vs. hematogenous
• ASCENDING are usually bacterial,
and chorionamnionitis
• HEMATOGENOUS
are often TORCH,
and villitis
130. Placental Neoplasms,
i.e. gestational trophoblastic disease
• Benign: MOLES (Hydatidiform moles)
• Malignant: CHORIOCARCINOMA
• BOTH are associated with increased or
persistent levels of the placental
hormone HCG
131.
132. (Hydatid)-iform Mole
• 1/1000 in USA
• 1% in Indonesia
• Also called NON-invasive mole in
its most common benign variant,
but can also be “invasive”
• Complete (2% chorioCA incidence)
or partial (0% incidence)
• Grapelike clusters, i.e., swollen villi
133.
134. The MAIN thing
differentiating benign
from malignant from
worrisome trophoblastic
neoplasms is
INVASIVENESS
of the trophoblast
Notes de l'éditeur
Johannes Müller
Müllerian first, everything else second!
Bartholin glands in women are analogous to Cowper’s (bulbourethral) glands in men. They are also called GREATER vestibular glands. Inflamation or obstruction to the ducts of these glands can cause cyst formation.
The GREATER vestibular glands are located on the LOWER (posterior) wall of the vagina.
The vestibular glands (NOT greater vestibular) are located on the UPPER (anterior) wall of the vagina.
“LSA” is the buzz word that all the cool people use who would like you to think they know a lot about this disease
Lichen Sclerosus et Atrophicus
“Sclerosus” refers to fibrosis of the underlying dermis.
“Atrophicus” refers to thin epidermis.
“Lichen” is Greek for “crusty”
This type of “lichenoid” disorder has HYPER-plastic epidermis, NOT atrophic., like most of the SKIN lichenoid disorders do.
The “hyperplasia” is felt to be related to “itching” or mechanical epidermal irritation.
This is probably because of the “promoter” concept again. It also sounds like more of a legal disclaimer, because itching shouldn’t cause cancer, right?
Yep, HPV again! (usually types 6 and 11)
VIN, CIN, PIN, VIN. (why a double “V”? (Vulvar,Vaginal too), all represent PRE-cancerous changes, vulva, cervix, prostate, vagina, respectively.
Soon you’ll see EIN, too for the endometrium.
Very LOW grade VIN looks almost like normal skin, very HIGH grade VIN is regarded as carcinoma-in-situ, i.e., cancer, but hasn’t infiltrated yet.
Identify the areas of VIN on this picture.
Factures such as loss of maturation pattern, nuclear aberrations such as enlargement, hyperchromasia, pleomorphism, mitoses differentiate LOW fro HIGH.
INFILTRATING squamous cell carcinoma. Any doubt?
Any doubt? INFILTRATING squamous cell carcinoma!
Radical vulvectomy specimen? How do you know this is malignant melanoma? Where is the pigment? Would you order a S-100 and HMB-45 immunostain? Answer: YES
Why are some of the WORST melanomas not grossly (or even microscopically) pigmented?
Atresia, double vagina, double uterus.
Bacteria, Candida, Trichomonas are the common causes of vaginitis
Note the trich’s flagella, wet prep, SEM in lower right.
A specific subtype of adenocarcinoma ("Clear Cell") occurs in a small percent of women (termed "DES-Daughters") born between 1938 and 1973 (later outside the United States) that were exposed to the drug diethylstilbestrol (DES) in utero
Yep, you guessed it. Caused by HPV again, usually.
Squamous metaplasia of cervical glands.
Can you understand how this might be difficult to differentiate from infiltrating squamous cell carcinoma?
Cancer or metaplasia?
Ans: Cancer
Why?
The old name “botryoid” rhabdomyosarcoma, is still often used. Sarcoma botryoides, or botryoid sarcoma.
IS “botryoid” the Greek root word for “grape bunches”? Ans: YES
Can rhabdomyosarcomas arise from mature skeletal muscle? ANS: NO
Skeletal muscle precursor cells? YES
Colposcopist’s view. Where, precisely, is the squamocolumnar junction?
What is this? This is the visual LEAP between gross and miscrsocopic, We can also see the PRECISE squamocolumnar junction microscopically too.
What is this? How is an N/C ratio reflective of serum estrogen levels?
Is a PAP smear a great test of estrogen level? Ans: YES
This is precisely the squamous metaplastic process? Where else might squamous metaplasia occur and why?
MANY neutrophils often accompany mature squamous cells on pre-premenopausal pap smears, Do NOT be fooled into thinking some inflammatory process is going on which needs to be treated.
What is your diagnosis?
Cancer?
Breech presentation?
HPV?
Polyp?
Answer: Polyp
Glands and fibrous stroma of a typical cervical polyp.
Because it has GLANDS, would you call it an ENDO-cervical polyp, rather than ECTO-? Ans: YES
Are most cervical polyps ENDO_cervical? Ans: YES
Note that the journey from normal epithelium to carcinoma is a GRADUAL one, often many years too. Sometimes, only MONTHS!!!!!
Which one is “worse:?
Which one is more convincingly HPV? Why? (Ans: Koilocytosis)
Would you expect microinfiltration to originate from a carcinoma-in-situ appearing epithelium?
Ans: YES
The “infiltration” on the right may NOT look grossly infiltrated.
Normal, CIN-I, CIN-II, CIN-III.
Which is which?
A classic by Noyes!
PRE-ovulatory = proliferative endometrium.
POST-ovulatory = secretory endometrium.
If you diagnose “SECRETORY ENDOMETRIUM”, what have you proven? Ans: the woman has ovulated
What is the greatest concern in POST menopausal bleeding? Ans: CARCINOMA
What is the difference between adenomyosis and endometriosis?
Is adenomyosis also called endometriosis “IN-terna”? Ans: YES
Is endometriosis called endometriosis EX-terna? Ans: YES
What are these hemorrhagic areas in the thickened myometrium? Ans: ENDOMETRIOSIS
Endometriosis, rectal.
“Chocolate” refers to the consistency of the hemorrhage, nothing more.
So therefore, not all “chocolate” cysts are due to endometriosis.
Endometrial “polyp”, colposcopist’s view and gross specimen.
Endometrial “polyp”, microscopic view.
Because endometrial polyps are really excesses of estrogen targeted tissue, i.e., endometrium, are they related to estrogen excesses? Ans : YES
Are they related to hyperplastic endometrium? Ans: YES
Can they be confused with hyperplastic endometrium on a D&C specimen? Ans: YES
Although they can be functional glands, i.e., show cyclic changes, most are in postmenopausal women.
Polyps vs hyperplasia? Does it matter?
In each case it is a functional hyperplastic proliferation of endometrium.
Just as NUCLEOLI differentiate benign from malignant prostate glands, what differentiates benign from malignant smooth muscle tumors?
Ans: MITOSES per high power fields.
NOT pleomorphism,
NOT hyperchromasia,
NOT nuclear size,
…………………………………..But MITOSES!!!
INVASIVENESS is KEY feature to differentiate endometrial hyperplasia from endometrial carcinoma.
What are the usual glandular features of adenocarcinoma vs. “benign” glands?
These are merely adjectives, HOWEVER, some types are better than others, prognostically.
HOWEVER, grading and staging are of utmost importance, independent of whatever of these “adjectives” you use.
Primary germ cells, male or female, first arise in the yolk sac and migrate to the genital ridge, which is in close proximity to the mesonephros.
Eventually, retroperitoneal testes migrate through the inguinal canal to the scrotum, covered by peritoneum.
Ovaries stay in the pelvis, and are covered by serosa, and are therefore intraperitoneal, but POSTERIOR to the fallopian tubes.
The CORTEX is the site of developing follicles.
The MEDULLA is relatively free of developing follicles, and rich in connective tissue (stroma) and blood vessels.
Major internal female genitalia structures, landmarks, and interrelationships.
In which ligament does the ovarian artery lie?
Through which structure does the round ligament travel.
Normally the uterus is a bit ANTE-VERTED and ANTE-FLEXED
Major internal female genitalia structures, landmarks, and interrelationships.
GREAT whole mount to demonstrate overall cortex vs. medullary differentiation.
Zona pellucida, arrow, becomes “atretic” follicle.
Is this a primary follicle? Ans: YES Why?
Secondary = Graffian = Antral follicle
Where is the antrum?
Find the cumulus oophorus, liquor folliculi, and corona radiata
Granulosa and theca INTERNA cells make estrogen.
LUTEAL cells, under LUTEINIZING hormone and FSH too, make progesterone.
LUTEUM means YELLOW. Why? Why is ANYTHING bright yellow?
A corpus luteum of pregnancy is considerably larger than a regular, NON-pregnancy, corpus luteum, often, perhaps about a half or third the size of the ovary itself.
Corpus albicans.
ALBA means WHITE.
Why is it white?
Most common PRE-menopausal cyst.
Any EXTREMELY yellow cyst of a premenopausal ovary, is regarded as luteal in origin.
Very common PRE-menopausal cyst
Although the cortical area of the normal ovary contains cysts, i.e., various stages of follicular development, true PCOD (PolyCystic Ovarian Disease, or Stein-Leventhall) ovaries are BIGGER (2x) than normal premenopaosal ovaries and have “true” cysts, NON-ovulatory, NOT just stages of follicular development.
Is a “cyst” a “tumor” (i.e. swelling) in the classical sense of the word, like a bump on the head. Is a cyst usually a true neoplasm? Ans: Of course not!
Always think of true ovarian tumors as following the normal anatomy/histology in these FOUR groups---mullerian, germ, sex-cord, metastatic.
In contrast to the testicle, the ovary DOES occasionally get metastases.
Gross, microscopic, physiologic, behavioral classification factors for ovarian tumors.
The HUGEST tumors ever reported in human beings (50-100 lbs.?) are frequently benign mucinous ovarian tumors.
Q: What other adjective can we give to this tumor besides serous? Ans: Papillary
Benign or malignant? Ans: Donno
Close up of papillae
Why is this serous and NOT mucinous?
PSAMMOMA bodies
Ovary, thyroid, breast, meningiomas, any place where papillary adenocarcinomas are found.
Serous and mucinous
Less common Müllerian tumors, all malignant except for one (Brenner)
I TOLD you this looks the same as TESTICULAR germ cell tumors.
Dermoid “cyst” = BENIGN CYSTIC TERATOMA, BY FAR the most common ovarian NEOPLASM of younger women, usually BENIGN
Whether the teratomatous elements are “mature” or “immature” determine, greatly, the behavior of the teratoma, i.e., benign or malignant.
IMMATURE looking neural tissue.
This is much more likely to behave badly (i.e., malignant) than a mature one.
Often, you might see retinal tissue, like you see here.
Female dysgerminomas are IDENTICAL in appearance to male seminomas, i.e., germ cells + lymphocytes. You’d have to tell the pathologist whether this was a male or female in order for him to diagnose seminoma vs. dysgerminoma.
Schiller-Duvall Body, just like in the testis yolk sac tumor!
EXACTLY the same as a malignant HCG producing testicular choriocarcinoma or a malignant HCG producing placental choriocarcinoma
“Sex cord” = “stroma”
MANY are functional, i.e., associated with hyper estrogenism (or androgenism)
Call-Exner bodies are virtually diagnostic of granulosa cell tumors.
Q: Do they remind you of “rosettes”? Ans: YES
Q: Would a “thecoma” derived from theca INTERNA be more likely to be functional than a thecoma derived from theca EXTERNA? Ans: YES
Why?
Note the “theca” has both a vesicular and spindle cell appearance. The juicy vesicular cells, theca interna, and tumors derived from them, can secrete estrogen. The spindly theca externa cells, usually do not, and may look simply like fibromas.
Many thecomas look white and fibrous, That is why the term fibrothecoma is often used?
Is a fibrothecoma or fibroma less likely to be functional than a thecoma? Ans: YES
Why? Ans: It is derived from characteristically NON-estrogen producing cells.
Not separated 3 ways, as in trimesters, but TWO ways, early and late.
Most tubal pregnancies occur in week 5-8 of pregnancy, does this one look a but later? Would you think the hemorrhage might be retrograde before it ruptures the muscular wall?
Normal ~500 gram placenta.
Might this umbilical cord insertion be a little eccentric? YES, Velamentous? NO
Accessory placental lobe.
An extreme lobe might be called a BI-partite placenta.
In a circumvallate placenta the amnionic, i.e., amniotic, membranes “thicken” or “double back”.
Incidence: 1%
Associations: Abruptions, Oligohydramnios
You might guess this kind of placenta would be VERY difficult to remove, and remnants (retained POC) might result in endometritis. If the decidua is a cushion between placenta and uterus, then accreta means loss of cushion.
ACC-reta, IN-creta, PER-creta, in order of severity.
And don’t forget placenta “abruptio” or premature separation of placenta with hemorrhage (i.e., hematoma)
Twin zygosity (mon- or di-) is related to the number of CHORIONS, NOT amnions or umbilical cords!
Toxemia of pregnancy occurs in an amazing 6% of all pregnancies. Toxemia is also called PRE-eclampsia.
When PRE-eclampsia is particularly severe and associated with more serious systemic effects such as DIC or convulsions, it is called ECLAMPSIA.
Wee now return full circle back to chapter 10, diseases of childhood!
What does TORCH stand for?
T-oxo
O-ther
R-ubella
C-MV (Do you see the BASOPHILIC intranuclear inclusion in the above villitis pic?)
H-erpes
Syncytial cells are FUSED, CYTO-trophoblastic cells are deeper stem cells.
Is this chorionic villus mature or IM-mature? Ans: mature
Why? Ans: It has blood vessels in its core. If it was IMMATURE, it would NOT need secondary blood vessels and can diffuse oxygen and nutrients WITHOUT secondary blood vessel formation.
In COMPLETE moles, ALL the villi are swollen. They turn into choriocarcinomas 2% of the time.
In PARTIAL moles, only some are. They NEVER turn into choriocarcinomas.
NOTE trophoblast looks NORMAL, i.e., NON-invasive and NON-proliferative, and NON atypical.
How does the TROPHOBLASTIC layer look on the right, uniform and thin, or invasive and thick? Ans: Uniform.
Choriocarcinoma. Note invasive trophoblast.
Choriocarcinoma. Note extreme pleomorphism of trophoblastic cells.