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Repro GI wk 2

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Primary Syphillis
Treponema Pallidum (spirochete). Inflammatory cells, necrotic debris. Highly infectious chancres. Nonsupporative, nonpainful lymphadenopathy.
Secondary/Tertiary syphillis
Secondary – 6-8 weeks after infection – maculopapular skin rash, condyloma lata (looks like accuminatum). Systemic symptoms, bacteremia. Tertiary – Yrs later. Aortitis, CNS lesions, tumorlike lesions
Granuloma inguinale – Infection, Clinical, Histo
Calymmatobacterium Granulomatis (Gram neg, encaps) infection. Dense dermal infiltrate w/ necrosis & pseudoepitheliomatous hyperplasia. Histo – Donovan bodies – small round encapsulated bodies in the cytoplasm
Lympogranuloma venereum
Clamydia trachomatis infection of lymphatic vessels. Ulcer at contact site & stellate absecesses w/ wpithelioid histiocytes
Condyloma accuminatum
Venereal warts. - Koilocytes, thickened skin, hyperkeratin, nucleated keratin. (6& 11 are not associated w/ cancer)
Molluscum Contagiosum
Pox virus. Verrucous epidermal hyperplasia. Molluscum bodies in stratum granulosum & stratum corneum. Seen both as STD and in pediatrics.
Trichomonas Vaginalis
Flagellated trophozoite. Purulent vaginal discharge, fiery red mucosa (strawberry cervix)
Two vulvar dystrophies
Squamous hyperplasia, Lichen Sclerosis.
Squamous hyperplasia
Hyperkeratosis, thickened epidermis, dermal inflammation
Lichen Scelerosis
Hyperkeratosis, edema, telangiectasia, white macules/papules. Thinned epidermis, area of sparing, inflammation.
Cervicitis
Both acute and chronic. Estrogen --> glycogenation --> increased bacterial growth. Can induce squamous metaplasa
Histology of cervix/vagina
Cervix – columnar, Vagina – nonkeratinized squamous
Endocervical Polyps
Inflammatory tumor w/ irreg vaginal spotting. Soft mucoid lesions often found incidentally. Tx = excision.
High risk HPV serotypes
16, 18, 31, 33
Mechanism of high risk HPV
Proteins E6 or E7 accelerate degradation of p53. Also, E7 blocks RB gene, p21. All end up blocking apoptosis.
CIN
Cervical equivalent of carcinoma in situ. Graded 1-3
VIN
Vulvular equivalent of carcinoma in situ. Graded 1-3
SIL
Cytopathologic equivalent of CIN. Not definitive.
Differences in high grade CIN
Reduction in cytoplasm, increased nucleus, loss of organization
Cervical Squamous cell carcinoma
End product after grade 3 CIN. Invasive.
Two types of Vulvar SCCA
HPV associated, Vulvar dystrophy associated (assoc w/ p53)
VAIN
Vaginal Intraepithelial neoplasia. Vaginal eq. Of carcinoma in situ. Related to high risk HPV
DES exposure is associated with which cancer
Vaginal adenocarcinoma. (benign, but can progress to clear cell adenocarcinoma)
Vaginal adenosis
Benign glands found in vagina (shouldn't be there)
Embryonal Rhabdomyosarcoma
(Sarcoma botryoides) Polypoide grape like clusters found in infants/children.
Extramammary Paget's Disease
Looks like paget's disease of the breast. Pruritic red lesion on labia. May be ass. W/ submuc thickening or tumor. Large clear tumor cells in epidermis
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Proliferative phase endometrium
Tubular glands w/ pencil shape nuclei
Early Secretory Endometrium
Sub or supranuclear vacuoles, secretion, stroma similar to prolif.
Midsecretory endometrium
Maximal stromal edema, maximal glandular secretion
Late secretory endometrium
Abundant cytoplasm, round nuclei in stroma (Predecidual).
Menstrual endometrium
Stromal collapse, hemorrhage, exhausted secretory glands.
Anovulatory Endometrium
Proliferative, but hemorrhage and stromal collapse (apoptotic bodies)
Inadequate luteal phase
Common cause of infertility due to inadequate progesterone. Histologic date lags clinical date.Change in bleeding.
Endometriosis
Presence of endometrial tissue outside of the uterus
Adenomyosis
Endometrial tissue in the myometrium. Makes cystic spaces.
Mechanisms of endometriosis
Retrograde flow, lymphatics, etc. or inappropriate Meullerian differentiation
Two types of endometrial polyps
Proliferative endometrium and hyperplastic endometrium.
Endometrial polyps
Fibrotic stroma & thick walled vessels. Sensitive to estrogen (not progesterone)
PTEN gene
Loss of causes endometrial hyperplasia
Simple endometrial hyperplasia
Looks like normal endometrium, but too much (glands:stroma = 1:1). Increased variation in gland diameter
Complex endometrial hyperplasia
Increased gland:stroma ratio. Atypical rounded nuclei w/ nucleoli
Endometrial Adenocarcinoma
Most common invasive carcinoma. Risk: Obesity, diabetes, HT, infertility. Significant polypoid projections.
Type I vs Type II endometrial carcinoma
Type I: Pre/Perimenopausal, unopposed estrogen, precursor hyperplasia, minimal invasion, stable. Type II: Postmenopausal, no unopposed estrogen, high grade, deep invasion, progressive
Endometrioid carcinoma
From type I endometrial carcinoma. Looks like endometrium, maybe squamous diff
Type II endometrial carcinoma – advanced
Becomes Serous Papillary carcinoma (p53) or Clear Cell carcinoma. Bad prognosis
MMMT
MMMT – Malignant Mixed Mesodermal Tumor – Endometrial adenocarcinoma. Looks like muscle, forms spindles. Heteralogous = skel muscle/bone Homologous = smooth muscle/endometrial stroma
Endometrial Stromal Tumor
Nodule – Well circumscribed aggregate of endometrial stromal cells. Sarcoma – Invasive version (t(7:17))
Adenosarcoma
Benign endometrial glands w/ malignant stroma. Better prognosis
Leiomyoma
Fibroids. Common, often multiple. Benign. May disseminate, but not cause death
Leiomyosarcoma
From myometrium or endometrial stroma. Often metastasize. Bad prognosis. Typical findings for aggressive disease.
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4 types of neoplastic ovarian disease
1. Surface epithelial stromal tumors. 2. Sex cord stromal tumors. 3. Germ cell tumors 4. Metastases
Follicle cysts
Non-neoplastic, from graafian follicles. May cause increased estrogen.
Corpus luteum cysts
Non-neoplastic, persistance of corpus luteum. Remove laproscopically
Polycystic ovarian disease
Causes: Oligomenorrhea, obesity, hirsutism, persistant anovulation. Not well understood.
Surface epithelial-stromal tumors (ovarian)
Normal sized ovary w/ serous lined cysts.
Types of epithelial ovarian tumurs
1. Serous – looks like fallopian tube (low columnar) 2. Mucinous – looks like endocervix or colon. 3. Endometrioid: looks like prolif endoemtrial glands 4. Clear cell 5. transitional- Resembles transitional urothelial cells
Serous Cystadenoma
Benign tumor. Large w/ serous lining. Remove laproscopicaly
Serous Papillary tumor
Borderline malignancy, not malignant or invasive, but don't remove laproscopically. More irregular lumen.
Serous papillary cystadenocarcinoma
Looks like papillary, but glands invade stroma.
Mucinous ovarian tumors
Second most common (25%). 85% Benign or borderline. Middle adult life
Mucinous cystadenoma
Bening mucinous. Endocervical mucinous epithelium
Mucinous cystadenocarcinoma
Malignant version of mucinous cystadenoma. More solid growth w/ intestinal type epithelia. Cellular atypia & stratification
Pseudomyxoma Peritonei
Mucinous neoplasm on peritoneal surface. Often from appendix, but metast to ovaries.
5 genes implicated in ovarian cancer
1. BRCA1 2. BRCA2 3. BRAF 4. TP53 5. KRAS
Which gene is implicated in mucinous tumors?
KRAS
Which genes are implicated in serous carcinoma
All 5
Which genes are implicated in endometroid carcinomas?
CTNNB1, PTEN
Teratoma (mature)
Always benign. Shows random mature tissues
Teratoma (immature)
Potentially malignant. Grading based on immature neuroepithelium.
Dysgerminoma
Nodular tumor w/ fibrous septae. Clear 'fried egg' cells. Equivalent of seminoma in testes.
Yolk sac tumor
“endodermal sinus tumor” releases a-fetoprotein. Schillar-duval bodies
Ovarian Choriocarcinoma
Histologically identical to placental lesion – syncitio, cytotrophoblasts. High B-hCG. Aggressive, unresponsive to chemo
Ovarian Fribroma/Thecoma
From stroma of ovary. Inhibin positive, spindle cells on histo stain.
Krukenberg Tumor
Metastises from mucinous carcinoma. Signet ring cells.
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3 causes of Urethritis
Neisseria Gonorrhoea, Chlamydia Trachomatis, HSV
N. Gonorrhoeae – Morphology
Gram Neg diplococci
N. Gonorrhoeae – Pathogenicity (4)
Pili – adherence & variation. Opa – allow internalization IgA1 protease Endotoxin
N. Gonorrhoeae – Clinical disease (5)
Urethrites w/ mucopurulent discharge. Disseminated – Fever, polyarthralgia, septic arthritis, rash PID Epididymitis/prostatitis Gonococcal opthalmia
N. Gonorrhoeae – Agars
Mueller-hinton or Thayer-Martin
N. Gonorrhoeae – Treatment
PENICILLIN, ceftriaxone, cefixime, ciprofloxacin, ofloxacin. (Also treat for chlamydia)
Chlamydia T. - Morphology
Gram neg, obligate intracellular
Chlamydia T. - Serovars (and disease)
A,B,C – Endemic Trachoma. D-K – Chlamydia, L1-3 LGV
Chlamydia T – Lifecycle
Elementary body – inert, extracellular. RB – Intracellular
Chlamydia T – Pathogenicity
Lifecycle & Type III secretion
Chlamydia T – Disease
Urethritis (less severe than N.G.), epididymitis, prostatitis, PID, Inclusion conjunctivitis, LGV
LGV
Lymphogranuloma veneruem – Ulcerative lesion followed by tender inguinal lymphnodes.
Trachoma
Chlamydial infection of the eye. Causes blindness
Chlamydia T – Treatment
Azithromycin, doxycyclin. (Or levoflaxacin, erythromycin, levoflaxin)
Which diseases cause lesions of the genitalia (5)
Trep Pallidum, H. Ducreyi, C. Trachomatis (LGV) HSV, HPV
T Pallidum – Morphology
Very small Spirochete.
T Pallidum – Primary disease
Nontender ulcerative lesions
T Pallidum – Secondary disease
General rash, esp soles and palms. Nontender enlarged lymphnodes
T Pallidum – Tertiary disease
Paresis (cogn., pers changes), Tabes dorsalis, cardiovascular syphillis, gummas
T Pallidum – Tests
Nontreponomal (VDRL, RPR) for screen, Treponomal (FTA-ABS, MHA-TP) for diagnosis.
Syphilis – treatment
PENICILLIN, or doxycyline/tetracycline. Also test for HIV
H Ducreyi – clinical
Chancroid – genital lesions w/ tender inguinal nodes & shaggy border
Herpes – Treatment
Acyclovir
Causes of Vaginitis (6)
C Trachomatis, N gonorrhoeae, HSV, T Vaginalis, bacterial, yeast, Dave Rosenthal
Trichomonas Vaginalis – morphology
Pear shaped protozoan. Flagellated & motile.
Vaginitis – clinical
Malodorous yellow/green discharge, itching, dysuria, urination, dyspareunia, strawberry cervix.
T Vaginalis – treatment
Flagyl
Bacterial Vaginalis
Disruption in bacterial flora of vagina displaces lactobacillus, raises pH
Bacterial Vaginalis – treatment
Metronidazole or clindamycin
PID
Ascending infection of N.G., C.T., or others. Causes infertility/ectopic pregnancy. Also mucopurulent discharge, pain.
PID typical treatment
Doxycycline (for C.T.), cefoxitin (for anaerobes)
Causes of epidymitis
C trachomatis, N gonorrhoeae
Causes of cervicitis
C Trachomatis, N gonorrhoeae, HSV
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What is the most common STD?
HPV. (Second is probably Chlamydia)
Which STD is most easily transmitted?
Gonorrhea
Which cell type do Gon. & Chlam infect?
Columnar epithelia.
Which cell type does HIV infect?
Langerhans, CD4+ or CCR5+ immune.
What increases susceptibility to HIV (3)
STD's, Hormones, Progesterone (estrogen decreases)
Two STDs that are passed transplacentally
HIV, Syphillis
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HIV – GP120
Binds CD4 receptors (necessary but not sufficient)
3 required receptors in HIV tx
CD4 CCR5, CXCR4
In utero vs intrapartum HIV transmission risk
In utero – 25-40% intrapartum – 60-75% (additional risk in breast feeding)
MAC
Mycobacterium Avium. Presents w/ disseminated multi organ infection (fever, night sweats, weight loss, fatigue, diarrhea, abdominal pain)
IRIS
Immmune Reconstitution Inflammatory Syndrome – Acute systemmic inflammatory response when imune system is recovering under ARV therapy.
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