High Risk in HPV to cause cancer?
-16,18,31,33,35
Low Risk Cancer, High Warts for HPV?
-6,11
Is HVP a DNA or RNA virus?
DNA
Molecular Pathology of Cervical Dysplasia/CIN/SIL
- high risk HPV E6 & E7 genes are important in development of high grade dysplasia and invasive cancer
- E6 gene product binds to and causes degeneration of the p53 (tumor suppressor) protein
- E7 gene binds/inactivates Rb protein, allowing up-regulation of Cyclin E and p16INK4
- lifespan of epithelial cells increases
- Koilocytotic changes (condyloma), dysplasia and cancer
Original Squamous Epithelium of Cervix
- smooth, shiny, featureless
- very fine vessels
- sharp squamous columnar junction separates the squamous epithelium from villous endocervix
Appearance of Epithelium of CIN/SIL
-add acetic acid and it turns white
Appearance of Invasive Squamous Cell Carcinoma
- nodular, with bizarre vessels and areas of hemorrhage
- if endophytic: cervix is barrel-shaped
- bleeds with acetic acid, does not stain with iodine
Features of Koilocytotic Change
- Cytomegaly
- Nucleomegaly
- Perinuclear Halo
- Irregular Nuclear Membrane
- Stipples (coarse) chromatin
- Increased mitotic activity
CIN I - Pap Smear
- mild dysplasia
- changes are seen in basal third of squamous epithelium
CIN II - Pap Smear
- moderate dysplasia
- lower and middle third of epithelium, still some epithelium differentiation
CIN III - Pap Smear
- severe dysplasia
- minimal differentiation in superficial epithelium
Microscopic Koilocytotic Changes
- epithelial cells with crisp, perimuclear intracytoplascmic halos
- nuclear mem is irregular resulting in wrinkled nucleus w/viral particles
Flat Condyloma with Koilocytes
- cells in intermediate layers are ballooned with copious clear cytoplasm in which viral particles reside
- once cell binucleated
Features of Intraepithelial Dysplasia/CIN/SIL
- maturation arrest (dec./missing superficial epithelial cells)
- blurred or missing distinction of basal cell layer
- loss of cellular orientation, polarity
- increased nuclear/cytoplasmic ratio
- hyperchromatic epithelium
Invasive Squamous Cell Carcinoma - Micro
- invading irregular squamous cell nests
- dysmoplastic stroma, irregular squamous nests with keratinization (sometimes)
Cervical Invasive Squamous Cancer
- predominately squamous cell carcinoma
- leading cause of cancer deaths in women 50y/o
- 8th cause of cancer deaths
- survival depends on clinical stage
Stage I
confined to cervix
-85-90% 5 year survival
Stage II
- local invasion
- 75% 5 year survival
CIN RIsk Factors
- early age at first intercourse
- multiple sexual partners
- a male partner with multiple previous sexual partners
- high parity, family history, other virusis
- immune status
Screening for Cervical Cancer
- Exfoliative cytology of cervix (pap smears)
- Bethesda nomenclature: normal, benign changes, LSIS, HSIL, ASCUS (atypical squamous cells of undetermined significance), atypical glandular cells, other
Micro CIN I
- large
- nucleus is hyperchromatic
- raisinoid and binucleated or multinucleated
- low nuclear/cytoplasm ration
Micro CIN II
-high nuclear/cytoplasm ration
Micro CIN III
- small cells
- very high nuclear/cytoplasmic ratio
Prevention of Cervical Cancer
- virus-like particles can be used to create & increase host immunity against HPV
- Increased immunity prevents HPV infection, dev of cervical dysplasia (precancerous condition) and cancer
- decrease HPV infection
Key to prognosis of Endometrial Cancer
-stage
Endometrial Cancer
-bleed earlier in cervical
Tumors of Uterine Corpus: Benign
- leiolyoma (smooth muscle)
- endometrial stromal nodule
Tumors of Uterine Corpus: Malignant
- adenocarcinoma of endometrium (endometrioid, serous papillary)
- mixed mullerian tumors
- leiomyosarcoma
- endometrial stromal sarcoma
Leiomyoma
- circumscribed nodules in myometrium
- white whorled surface
- cigar-shaped nuclei (smooth muscle)
Abnormal Uterine Bleeding
Baby girl: maternal estrogen
Post Menopause: tumor
Adenomyosis
-presence of benign endometrial glands and stroma within the myometrium
Endometriosis
- most common site is on ovary, then around ovary
- presence of benign endometrial glands and stroma outside the uterus
Ovarian Neoplasms/Surface Epithelial Stromal Tumors
-
Serous Tumors
Ovarian Neoplasms/Surface Epithelial Stromal Tumors
-cystadenoma
-cystadenocarcinoma
MOST COMMON 75%
Mucinous Tumors
Ovarian Neoplasms/Surface Epithelial Stromal Tumors
- cystadenoma
- cystadenocarcinoma
Endometrioid
Ovarian Neoplasms/Surface Epithelial Stromal Tumors
- adenocarcinoma
- epithelial-stromal tumor (mixed Mullerian tumor)
Transtional Cell Tumor
Ovarian Neoplasms/Surface Epithelial Stromal Tumors
-Brenner tumor
Benign Serous Cystadenoma
- large simple cyst, thin wall and serous fluid content
- epithelium is cuboidal-low columnar, ciliated
Serous papillary cystadenocarcinoma, gross
-tan-yellow-white with papillary projections and solid areas
Serous Carcinoma of Ovary
- invasive cell nests forming papillary fronds
- psammoma bodies are common
Ovarian neoplasma/sex cord-stromal tumors
- granulosa cell timors
- tumors of thecoma-fibroma group
- sertoli cell tumor
- sex cord tumors
Granulosa cell tumor, gross
-mustard-yellow with areas of necrosis
Granulosa cell tumor, microscopic
- coffee-bean shaped nuclei, nuclear grooves
- call-exner bodies (circular arrangement around a sparsely cellular space recapitulating ovarian follicle)
Mature cystic teratoma, gross pathology
-cystic mass with sebaceous content, hair, teeth
Mature cystic teratoma, microscopy
-keratin, skin, skin appendages and subcutaneous fat tissue
Placenta
-temporary organ connecting fetus and mother providing equivalent of respiratory services
Amnion
membranous sac surrounding fetus containing serous fluid essential for fetal development
Chorion
-plate-shaped tissue under part of amniotic sac containing fetal blood vessels that branch into villi projecting into space filled with maternal blood
Trophoblast
outter layer of blastocyst (from fertilized ovum) that implants in uterus and forms placenta
Decidua
outer layer of placenta that normally peels off myometrium and sheds with placenta
Syncytiotrophoblast
syncytium of cells forming outer covering of chorionic villi, which thin out their cytoplasm and let their clumped nuclei hang off villi in “syncytial knots” to minimize diffusion barrier
First Trimester Chorionic Villi
covered by double layer
inner cytotrophoblast layer and outer syncytiotrophoblast layer
Third Trimester Chorionic Villi
more efficient
-more blood vessels, less interstitium, thinner trophoblast covering
Ectopic Pregnancy
-implantation of placenta anywhere besides normal intrauterine location
(1 in 150)
90% in fallopian tube
-scarring from previous infection of tube, adhesions from appendicitis, endometriosis or surgery
Presentation of Ectopic Pregnancy
acute severe abdominal pain due to fallopian tube rupture and pelvic hemorrhage (6 weeks agter last menses)
-hemorrhagic shock, death
Diagnosis of Ectopic Pregnancy
-history, physical (signs of peritonitis), ultrasound, pregnancy test
Treatment/Prognosis of Ectopic Pregnancy
surgery, good with proper treatment
Spontaneous Abortion
Pregnancy loss before 20 weeks
- occurs in 15% of clinically recognized pregnancies but 22% more abort in first trimester
- 11% in 22-24y/o to 51% in 40-44y/o
Cause of Spontaneous Abortion in First Trimester
-Genetic
1/2 with chromosomal abnormalities
Causes of Spontaneous Abortion in Second Trimester
-Infectious
acute chorioamnionitis
Causes of Spontaneous Abortion in Third Trimester
-Vascular
uteroplacental insufficiency, commonly associated with pre-eclampisa
Recurrent Spontaneous Abortion
>/= 3 immunologic (25%) (antiphospholipid syndrome) anatomic (22%) endocrinologic (20%) microbiologic genetic unknown
-recurrent stillbirth associated with hypercoagulable states
Placenta Previa
implantation in lower uterus or cervix sometimes covering internal cervical os
-often results in severe bleeding, may result in placental rupture, massive bleeding, maternal death
Diagnosis/Treatment of Placenta Previa
ultrasound
C-section
Placenta Accreta
defective decidua, with adherence of villous tissue to myometrium
80%
Placenta Increta
defective decidua, with penetration of villous tissue into myometrium
15%
Placenta Percreta
defective decidua, with penetration of villous tissue through entire uterine wall
5%
Treatment of Placenta Accreta, Increta, Percreta
persistent postoartum
-hysterectomy, resection or oversewing
Hydatidiform Moles
- Abnormal gestations due to two sperm fertilizing one egg or 1 or 2 sperm fertilizing an “empty egg” with absent or nonfunctional DNA
- rare in US (1 in 1,000)
- east (1 in 100)
- women less than 20 or greater than 40
Complete Moles
diploid
Partial Moles
triploid
Morphology of Hydatidiform Moles
- cystic swelling of chorionic villi makes them resemble grapes
- trophoblast hyperplasia more prominent in complete moles (all the way around villi)
Diagnosis/Treatment of Hydatidiform Moles
- average 8.5 weeks from abnormal ultrasound showing diffuse villous enlargement or rapid and high beta-HCG
- Treated with curretage and monitoring beta-HCG to make sure its all out
Types of Twin Placentas
- Dichorionic Diamnionic
- Dichorionic Diamnionic (fused)
- Monochorionic Diamnionic
- Monochorionic Monoamnionic
Dichorionic Diamniotic Twin Placenta
-69% of twins
80% of these twins are dizygotic
Monochorionic Diamniotic Twin Placenta
- 30% of twins
- all twins are monozygotic
Monochorionic Monoamniotic Twin Placenta
- twin twin diffusion syndrome
- unbalanced vascular anastomoses in monochorionic placentas can cause one twin to get to much blood and the other to get to little
Twin-Twin Transfusion Syndrome
-death of deprived “donor” twin can send necrotic procoagulant material into the anastomoses threatening the life of the other twin and then the mother
Placental Infections: Hematogenous
TORCH T-Toxoplasm gondii O-Other (syphillis, HIV) R-Rubella (german measles) C-Cytomeglovirus H-Herpes Simplex Virus
ascending from vagina: acute chorioamnionitis
Toxoplasma gondii
-protozoan from cat feces, causes microcephaly, fever, rash, seizures in noenates
Other
-rare in US with prenatal care
Rubella
causes deafness, neurologic defects, cardiac malformations
Cytomegalovirus
- most common infection
- deafness and neurological defects, & jaundice
Herpes Simplex Virus
gotten from birth
- skin infection
- prevent with C-section
Acute Chorioamnionitis
-41% of women with premature rupture of membranes at <27 weeks and 15% at 28-36 weeks
-stages: maternal polys in intervillous space, then in chorion, then in amnion, then fetal polys in chorionic blood vessels (fetal vasculitis) where inflammation may lead to thrombosis b/c:
INFLAMMATION IS PROCOAGULANT
Funisitis
-extensive tan exudate (areas of congestion) on the amniotic surface, exudate and congestion of cord
Acute Chorioamnionitis: Infection
- assends from vagina and cervix
- mainly maternal neutrophils (so starts in intervillous space)
- causes premature rupture of membranes (PROM) and premature labor and delivery
- polymicrobial, with multiple vaginal flora bacteria
Acute Chorioamnionitis Syndrome
-fever, tachycardia (fetal/maternal), uterine tenderness, foul smelling amniotic fluid and leukocytosis
Acute Chorioamnionitis Diagnosis/Treatment
- Diagnosis is clinical
- Treatment: antibiotics and delivery
- Prognosis: usually good, but can cause fetal sepsis, cerebral palsy, endometritis
Acute Abdomen (surgical emergencies) Causes
- ruptured ectopic pregnancy
- corpus luteum rupture & hemorrhage
- pelvic inflammatory disease
- appendicitis
- ovarian torsion
Ovarian Torsion
twisting on ligamentous support, cutting off venous outflow and then arterial inflow, causing ischemia and then infarction
-most common in women of childbearing age with ovarian mass or pregnancy (more in first trimester)
Ovarian Torsion Symptoms/Treatment
- acute onset of moderate-severe pelvic pain, often with nausea and vomiting
- treat with surgery
Appendicitis
- inflammation of appendix due to overgrowth of normal flora trapped by occluding fecalith
- 1 in 800 pregnancies (more in 2nd trimester)
- periumbilical abdominal pain that migrates to right lower quadrant, anorexia, nausea, vomiting, fever with McBurney’s tenderness, rebound tenderness
Volvulus
-twisting with intermittent cramping lower abdominal pain, progressive abdominal distension, passing no stool or flatus, with marked abdominal distension and tympany
Treatment of Volvulus
-untwisting by inserting tube
Diverticulitis
inflammation of transmural outpouching of colonic mucosa due to perforation +/- abscess
- common in elderly
- abdominal pain, often > day, left in 70% whites, right 75% asians, constipation 50%, nausea + vomiting, diarrhea, tenderness & leukocytosis