Path Flashcards by Lauren Gruenebaum

What are the 6 most clinically relevant gram positive bacteria?

Hint: two cocci, four bacilli

Cocci
-Staph
-Strep
Bacilli (rods)
-Non-sporeformers: Corynebacterium diptheriae, Listeria monoctyogenes
-Spore-formers: Bacillus sp., Clostridium

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What are the rest of medically relevant bacteria (not gram +)?

Gram -
Ex: Syphillus (Treponema palledum): Dark field microscopy, inclusion stains
E. coli

Special staining

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In terms of organisms, which of the following tend to cause the majority of salient diseases?
A) Bacteria
B) Viruses
C) Fungi
D) Parasites
E) Prions

A and B!

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What are the most clinically relevant organisms as related to salient categories/types of infx, issues related to acquisition, and gender?

-Staph (TSS tampons)
-Bacterial UTIs (females): E. coli
-Non-specific urethritis (NGU): purulent Chlamydia, Ureaplasma urealyticum, S. saprophyticus
-Vaginitis:
Bacterial=Gardnerella vaginalis
Fungal=Candida
Parasitic protozoan=____________
-Prostatitis
-Gonorrhea in men=purulent d/c–>epididymus hurts…risk of septic arthritis
-Gonorrhea in women=purulent d/c or asympt–>fallopian tubes–>infertility or septic arthritis
-Common STDS:
MC chlamydia (NGU, PID)
Gonorrhea (PID)
Syphilis
HSV
HIV
-Uncommon STDS:
Hemophilus decreyi: chancroid
Chlamydia: lymphogranuloma venereum
Klebsiella granulomatis: granuloma inguinale
-Enterococcus: hospitals

Trichomoniasis

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20 yo female presents w/ fever, high WBC w/ left shift, diffuse suprapubic pain, left lower back pain. Dysuria

Dx? Primary infection?

Bacterial infection of the bladder
MC E. Coli

(left shift=incr neuts=bacterial)

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Microorganisms–>Dz

1) Microbial flora: coexist, may–>infx
2) Pathogenic, non-commensal (small or large dose–>dz)

Routes of Entry:

1) Epithelial surface
2) Inhalation
3) Ingestion
4) Sexual transmission

Respiratory, GI, GU infx caused by ______ mircoogranisms that can penetrate epithelium

virulent

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Urine is sterile….anatomy=role in risk of UTI (women>men)…Obstruction or flow or reflux compromises normal defenses and increases susceptibility to urinary tract infxs…
Ex?

- Uterine prolapse

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Antibiotics can kill the lactobacilli and allow overgrowth of yeast–>_________
Minor trauma (sex)–>expose immature prolif epithelial cells susceptible to infx by HPV

candidiasis

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Host defense: urination
Breach: obstruction, microbial, attachment, local prolif

Ex?

E. coli

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Host defense: normal vaginal flora
Breach: Antibiotic use

Ex?

Candida albicans

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Host defense: normal vaginal flora
Breach: Microbial attachment and local prolif

Ex?

N. gonococcus

Chlamydia

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Host defense: intact epidermal/epithelial barrier
Breach: direct infx/invasion

Ex?

Herpes (MC ulcerating dz in world)

Syphilis

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Host defense: intact epidermal/epithelial barrier
Breach: Local trauma

Ex?

STIs including HPV, HIV

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Dx?

Bacitracin resistant, B hemolytic, colonizes vagina, causes pneumonia, meningitis, and sepsis mostly in BABIES
screen preg women at 35-37 wks
if + give penicillin

Group B strep

B=babies

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Meningitis/meningoencephalitis syndromes….setting/ages w/ organisms?

Listeria, E. Coli, Group B strep (neonates)
Consider N. meningococcemia (kids/young adults…petechial rash, waterhouse friderichsen syn)
H. influenza type B (+ epiglotittis)

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Gonorrhea in infants? children?

Infants: conjunctivitis
Children: abuse!

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Eye infx in infants and older children?

Chlamydia

risk–>blindness

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Fetal calcifications in the brain?

Cytomegalovirus
Toxoplasma gondii

(vertical transmission mom–>baby)

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Chanker not painful
Collapsed nose
Blind
Deaf

Congenital syphilis

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Uveitis
Arthritis
Conjunctivitis

Reiter’s syndrome (youths male)

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Monoarticular, septic arthritis in sexually-active young person?

Gonorrheal gram - diplococci

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Aplastic anemia?

Parvovirus, B19

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infx during 1st trimester
heart malformations
mental retardation
cataracts
deafness

Rubella
Placental-fetal transmission

(third tri little effect)

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-Transmission during birth includes what key examples?

Herpes, gonococcal, chlamydia conjunctivitis

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-Postnatal transmission in maternal milk includes...?

CMV, HIV, HBV

TQ - Cervical dysplasia and cancer (F) - Vulvar cancer (F) - Cancer of the penis (M) - Condyloma acuminatum (M/F) Dx?

HPV acuminatum (HPV 6 and 11....no SCC...see koilocytosis....16 and 18-->SCC)

``` TQ -Urethritis, cervicitis, salpingitis, PID (F) -Urethritis, epididymitis, proctitis (M) -Lymphogranuloma venerum (M/F) Dx? ```

Chlamydia trachomatis | resurgence due to co-infx with HIV

TQ - Cervicitis, endometritis, salpingitis, infertility (F) - Epididymitis, prostatitis (M) Dx?

Neisseria gonorrhea

- Chanker not painful | - No inflamed inguinal LN

Syphilis (T. pallidum)

- Painful chanker | - Inguinal LN swollen

Chancroid (H. ducreyi) | also painful in herpes!

- Chanker not painful - Inguinal LN swollen - strictures/fibrosis

Granuloma inguinale (Klebsiella granulomatis)

- Urethritis, balanitis (penis) - Vaginitis (F) - Greenish d/c, mobile protozoa

Trichomonas vaginalis

- Causes skin infx in immunosupp-->endocarditis | - Can become resistant-->flesh eating

Staph

- Causes pharyngitis-->PSGN | - MC community acquired pneumonia (esp in elderly)

Streptococcus

What is included in dx of ulcerating lesions of genital/inguinal region? NOT limited to GI or STDs!! (Bubonic plague=Y. pestis), francisella tularensis

Herpes, syphilis (USA), | Chancroid, G. inguinale, L. venerum (non-USA)

What dxx includes... Dysuria Urgency Frequency

- Chlamydia - Gonorrhea - Ureaplasma urealyticum - S. saprophyticus

Dx of | Syphilius vs CMV vs HSV on slide

Syphilis: Dark-field micro, inclusion stains CMV: intranuclear + cytoplasmic inclusions HSV: Intranuclear, multinucleated

CMV transmission?

- Transplancental - Neonatal (breastmilk) - Saliva (day care) - Genital route (15 yo)

HIV: - AIDS....who is at greatest risk of infx? - HIV is a non-transforming virus and is replicates via... Notes: Sex=dominant mode of HIV infx worldwide, semen-->abrasions in rectum/oral mucosa-->infx of CD4 cells....AIDS also infects B cells ``` Can also target CNS--enceph Phases: 1) Acute retroviral syn 2) Asymptomatic/chronic 3) Clinical AIDS ```

Men having sex w/ men Reverse transcriptase Has subgroups and clades

What are some AIDS-defining opportunistic infections and neoplasms found in pts w/ HIV?

Protozoa/helminth: Cyptosporidiosis, pneumocystosis, toxoplasmosis Fungal: candida, cryptococcus, disseminated coccidioidomycosis and histoplasmosis Bacterial: Mycobacterium, nocardia, salmonella) Viral: CMV, HSV, Varicella Neoplasms: Kaposi, primary lymphoma of brain, invasive cancer of cervix

32 yo male presents with sore throat, chronic diarrhea, and rt-sided painful rash....He thinks its the "flu that never went away". Lost wt. Fever. Oral candidiasis. Lower CD4 counts 480. Dx?

Chronic HIV infx Not acute: diffuse lymphadenopathy Not AIDS: multiple neoplasms with CD4 less than 200

37 yo white female complains of dyspareunia (pain with sex). Vulva/vagina ok but cervical erythema w/ focal, superficial erosions. Ki-67 positiove and p16. Dx?

HPV (cervicitis, erosions) NOT gardnerella b/c that would have vaginal pain

TQ T/F HPV is a transforming virus

TRUE-->SCC | HPV-16 and 18

TQ | 37 yo female has a low grade lesion. This reflects HPV infx which cells of the cervix?

IMMATURE, BASILAR SC (NOT mature!!) Basil prolif=malignant....CIN III=carcinoma in situ Cervical transition zone MC b/c immature basil prolif occurs here

What are the 2 routes for placental infections? 1) ascending through birth canal (MC)-->infx of membrane-->rupture-->preterm delivery 2) Hematogenous (transplancental)...ex?

``` TORCH Toxoplasmosis Others (syphilis, TB, listeria) Rubella CMV HSV ```

24 yo female complains of genital pain. Painful ulcerative lesino on left labia. Hx indicates sexual contact 4 days prior... Dx? What should it look like on smear?

HSV Multinucleated syncytia w/ bluish intranuclear inclusions Remember: granoluma inguinale and T. pallidum NOT painful

19 yo pregnant female. Distress. Cervix effaced/dilated. Membranes ruptured and amniotic fluid turbid w/ purulent exudates. SGA female infant 25 wks-->intubate. Cultures show TORCH...Which of the following is most likely ``` A. Toxo B. CMV C. Syphilis D. Listeria E. Rubella ```

D. Listeria! A and B) mom-->pre-labor calcifications in brain C) teeth, deaf, blind E) early in pregnancy

- pelvic pain + adnexal tenderness + fever + d/c | - Common causes?

PID - Chlamydia - Post-abortion/abnormal devliery (puerperal infx) - Gonococcus: 2 to 7 days after vaccination

``` 29 yo female seeks fertility consult. Been married 4 years and cannot conceive. Hx indicates sexual activity from early teens w/ multiple partners...Hysterosalpinogogram shows contrast media penetrating only a short distance laterally in both tubes...Most likely which of the following? A) Antecedent ectopic preg B) HPV 16, 18 C) Chlamydia D) Neisseria E) Herpes ```

C) chronic salpingitis (PID)-->infertility

MC cause of urethritis?

NGU! Chlamydia (also PID) | and ureaplasma urealyticum

17 yo female complains of significant vagina pain and itching...Insulin-dependent diabetes...vulvovaginal erythema w/ curd-like whitish discharge... Dx?

Candida albicans (immunocomp.) N. gonorrhea (purulent) Trichomonas (green) Chlamydia (asympt + serous d/c)

22 yo female in ED, shock, abd pain, diffuse lower abd pain w/ rebound (peritonitis). Purulent cervical d/c. Left knee swollen and red...Dx PID complicated by peritonitis/sepsis and suspect tubo-ovarian abscess... Dx?

Neisseria Septic arthritis!

A 17 G1P1 delivers male infant at 27 wks. SGA w/ desquamative rash of palms and soles...Vomer of nose flat and legs bowed. Hepatic transaminases elevated. Diffuse hepatocellular damage w lymphoplasmacytic infiltrates and focal obliterative endarteritis. Consult ophthalmology and audiology. Dx?

Treponema pallidum | def/blind-->chronic hep

- Inflammatory lesions of Bartholin glands may produce cysts. - They are tubuloalveolar glands that produce mucin - Contain watery or thick mucoid fluid, and / or become infected with what organism?

Gonorrhea! (gram-neg diplococci) When they heal, expect a cyst

- Chancroid of the vulva | - Gram-neg coccobacillus

Haemophilus ducreyi

- Changes in inflammatory reaction - Intracytoplasmic diplococci - Background of lactobacilli

Gonorrhea

- Purulent discharge of cervix | - Clear swollen cells

Chlamydia

- small pearly papules with central depression of the vulva - white cheesy material - painless/itchy lesions that may become inflamed, red, and swollen - pox virus inclusions (cup shaped with glassy nuclei pushing the nuclei to periphery)

Molluscum contagiosum Molluscum bodies=inclusions

- Tzank prep w/ papanicolaou stain - Three M's: 1) moulding of nuclei 2) margination of chromatin 3) multi-nucleated giant cells w/ ground glass nuclei (central viral inclusions)

Herpes Do a C section if preg

TQ - Histo: koilocyte (wrinkled nucleus) - Vulva: warts, intra-epithelial neoplasia, carcinoma

HPV chondyloma accuminata Low risk=6, 11 High risk=16, 18

TQ - most common lesion on the vulva - band of loose, pale-staning, collagen forms underneath the epidermis - Thinning of epidermis and fibrosis of dermis, hyperkeratosis, loss of rete ridges, dermal edema - **White scales, tissue paper appearance....gray and parchment-like or cigaret-paper-like and becomes itchy - Benign, but few percent turn malignant→SCC - Can cause leukoplakia (among other things)

Lichen Sclerosis (aka "chronic atrophic vulvitis”)

- Fungal infection of the vulva? | - see hyphae

Candida

- nonspecific condition resulting from rubbing and scratching of the skin. - Looks “like” leukoplakia. Vulva looks pink‐red like some one scratched it. Not premalignant. - Hyperplasia of the epidermis, thickening of the epidermis and hyperkeratosis

Squamous cell hyperplasia

TQ What stage of syphilis? -Separated, papular white lesions around vulva (wartlike) -Rash on hands and feet -Stromal fibrosis, squamous hyperplasia, chronic inflam., PLASMA CELL infiltrate

Secondary syphilis (condyloma latum) Reminder: syphilis=Treponema pallidum, a spirochete.

What stage of syphilis? -Chancre on vulva How do we visualize?

Primary syphilis Dark field micro, warthin-starry silver stain, immunofluorescence

TQ - White raised papules on vulva (papillary) - branching fibrous stalk with a thickened epithelium - Hyperkaratosis - Parakaratosis - Koilocytic atypia→koilocytic cells with dark/hyperchromatic, wrinkled nuclei (from all those extra copies of the viral genome) and a perinuclear clear zone (halo)

Condyloma acuminatum (HPV 6, 11)

- Most common BENIGN tumor of vulva - Presents as an ulcerated and bleeding nodule - Originates from exocrine sweat glands - Intraductal papilloma of the breast, only in the vulva along the embryonic milk line

Papillary Hidradenoma

- mucin-rich clear cells in the epidermis of the vulva or perineum with prominent nuclei/nucleoli - Gross sharply demarcated red, itchy, moist, crusted/ulcerated skin lesion - usually no underlying cancer - Cells: PAS +, Keratin +

Extramammary Paget's disease pagets of vulva→ usually no underlying cancer

Differential dx of extramammary Paget's disease?

Carcinoma vs melanoma - why melanoma? Malig population present in epidermis→ can also occur in vulva...make a distinction: is this carcinoma (pagets) or melanoma→ DO STAINS! - Paget cells: PAS +, Keratin +, and S100 – - Melanoma: PAS-, Keratin -, S100 +

TQ -Presents as leukoplakia→ have to biopsy to distinguish - Basaloid and warty, caused by HPV 16→ preceded by dysplasia [VIN (vulvar intraepithelial neoplasia)] and carcinoma in situ. Young pts - not caused by HPV →arise in long standing lichen sclerosis or idiopathic hyperkeratosis (these are more aggressive). Older people usually

Squamous Cell carcinoma

- residual glandular/columnar epithelium under the squamous epithelium in the upper vagina - Risk of adenocarcinoma - Assoc w/ hx of DES exposure

Vaginal adenosis

- Inclusion cysts in wall of vagina | - Wolffian duct remnants

Gartner duct cysts

- Nondysplastic - Noncondylomatous - No Koilocytic atypia

Squamous papilloma

-mature squamous epithelium overlying the benign appearing fibrovascular core

Fibroepithelial polyp | skin tags

- Primary carcinoma of vagina - Invasive - Precursor lesion=vaginal intraepithelial neoplasia (VAIN) (low or high grade) Ex: high grade vaginal intraepithelial neoplasia (incr epidermis and atypia)

Squamous cell Ca due to HPV 16, 18

TQ - MC vaginal sarcoma - Presents as bleeding and BUNCH OF grapes that protrude from vagina! Usually in girls

Embryonal Rhabdomyosarcoma (Sarcoma Botryoides)

What is the transformation zone?

Where the columnar epithelium of the endocervix meets the squamous epithelium of the ectocervix

What screen? - Endometrial cells in woman >40 yo - Epithelial cell abnormalities (atypical SC (ASC-US)), LSIL, HSIL, SCC - Glandular cell abnomralities (atypical endocervical cells) - Obtain the smear two weeks after the first day of the last menstrual periodo

- PAP smear is gold standard for screening→ scrape away cells from transition zone→ look for dysplasia (high N:C ratio), dark, hyperchromatic nucleus - Pap smear is good to detect SCC and precursor lesions

- Clue cells (fuzzy) in flora | - Vaginal pH is more alkaline (above 4.5)

-Bacterial vaginosis due to Garderella - Lactobacilli produce lactic acid which maintain the pH below 4.5. An alkaline pH is bad!!! - Infections may cause acute or chronic cervicitis causing reparative and reactive changes to appear in the PAP smear

- bad-smelling, red ("strawberry") inflammation with a thin discharge - wet mount: looks like a bouncing pear moving about with wiggly flagella (pears and whips) - On a pap smear, there is often a second micro-organism, a very long filamentous bacterium called "leptothrix". - Often the result of illess or poor hygiene

Trichomonas

- adenomatous, may cause bleeding - fibrous nubbins covered with epithelium, hanging out of the - They act as a wick, drawing bacteria into the endocervix and endometrial cavity.

Endocervical polyp

- Results from progesterone stimulation of the endocervix (i.e., pregnancy, old-fashioned contraceptive pills). - The glands are abundant and have only a lacy stroma between them, along with many neutrophils.

Microglandular hyperplasia

- superficial and intermediate squamous cells - mature squamous cells w/ production of large, resilient, cytoplasmic surface - endocervical cells have flat honeycomb cluster with clear cytoplasm. Irregular shaped nuclei with short protrusions

normal PAP

- Dysplasia of the cervix (“cervical intraepithelial neoplasia") - Due to PERSISTANT HPV infection - CIN I (LSIL) can regress (less likely with higher grades)→ can eventually become carcinoma in situ - L1 protein staining: - L1 staining still there→ maybe you can just watch - L1 staining lost→ likely to persist/get nasty What stage are each of these? 1) Koilocytes only (halo + atypia). Perhaps a condyloma acuminatum or a flat wart. (mild dysplasia)) 2) Plenty of atypical cells in the lower portions, normal maturation toward the surface (moderate dysplasia) 3) The cells no longer mature as they reach the surface (severe dysplasia)

- CIN I: Koilocytes only (halo + atypia). Perhaps a condyloma acuminatum or a flat wart. (mild dysplasia)) - CIN II: Plenty of atypical cells in the lower portions, normal maturation toward the surface (moderate dysplasia) - CIN III: The cells no longer mature as they reach the surface (severe dysplasia)

What type of Cancer? - arising from CIN III is usually squamous. - Carcinoma in situ becomes this - Presents as vaginal bleeding or post coital bleeding - New stain for p16 lights up the more aggressive intraepithelial lesions

INVASIVE CANCER

- See koilocytic atypia on PAP - low grade or high grade (invasive) - Ki‐67 and p16 IHC - Recall the E6 (p53) and E7 (pRb) proteins prevent cell cycle arrest.

HPV - Low risk HPV, 6, 11, 42, 43 - High risk HPV, 16, 18, 31, 33

Uterine defects: - prolapse - Bicornuate uterus - _______: variant of bicornuate. contains two cervixes

Didelphis

Which phase of the menstrual cycle? - contains small, quiet glands. -cells undergoing mitosis or stromal mitosis - some edema

Early proliferative stage

Which phase of the menstrual cycle? - glands start to get tortuous - some edema

Middle proliferative stage

Which phase of the menstrual cycle? - glands are now very tortuous - no edema

Late proliferative stage

Which phase of the menstrual cycle? | -Subnuclear vacuoles

Early secretory phase

Which phase of the menstrual cycle? - Exhaustion - disorganized

Late secretory phase

Which phase of the menstrual cycle? - Stromal break down - RBCS

Menstrual endometrium

Secretory Phase: Starts at ovulation (Day 14): - Day 14-16: glycogen vacuoles appear. - Day 19 or so: more secretion, and the glycogen and vacuoles are gone. - Day 20 or so: lots of secretion and begin to see stromal edema. - Day 22: maximal secretion, maximal sawtooth appearance of glands, but no decidualization. - Day 23-34: sawtoothing of glands, spiral arteries begin to nourish the fetus, predecidual reaction and lymphocytes - Day 24: great predecidua and lymphocytes. - Day 26: neutrophils, no pregnancy this month..... What will the baby make to keep the endometrium growing?

hCG | note: Guf says wont ask days but just review anyways...

What does most “dysfunctional uterine bleeding” result from? - common around menarche and menopause - results in estrogen-driven proliferative phase without progesterone-driven secretory phase - Endocrine disorders, ovarian lesions, metabolic disturb

Anovulatory cycles (failure to ovulate) Eventually get overgrowth of blood supply→ begin to degenerate and then there will be bleeding

What are some other causes of dysfunctional uterine bleeding?

Inadequate luteal phase - Infertility - Increased bleeding or amenorrhea - Decreased progesterone in the post ovulatory period

Age group related abnormal bleeding? -Prepuberty: precocious puberty (hypothalamic, pituitary, or ovarian origin) -Adolescence: Anovulatory cycle, coagulation disorders-->amemia -Reproductive age: -->Complications of pregnancy (abortion, trophoblastic disease, ectopic pregnancy) -->Anatomic lesions (leiomyoma, adenomyosis, polyps, endometrial hyperplasia, carcinoma) -->Dysfunctional uterine bleeding (anovulatory cycle, ovulatory dysfunctional bleeding (e.g., inadequate luteal phase) -Perimenopausal: dysfunctional uterine bleeding due to anovulatory cycle or anatomic lesions (carcinoma, hyperplasia, polyps) -Postmenopausal: Endometrial atrophy, anatomic lesions (carcinoma, hyperplasia, polyps)

Just look over...table from robins

- secondary amenorrhea due to loss of basalis→ scarring - Result of overaggressive dilation and curettage (D & C) → scrape away too much of uterine wall (scrape away basalis so you cant regenerate endometrium)

Asherman syndrome | intrauterine adhesions/scarring can cause pain and/or infertility

- Inflammation of the endometrium of the uterus | - Presence of microabscesses and / or neutrophils within the endometrial glands

Acute endometritis | may be staph or strep

- Inflammation of the endometrium - Incr plasma cells within the endometrial stroma - Abnormal uterine bleeding - Pelvic pain - Infertility

Chronic endometritis

Common causes of chronic endometritis? PLASMA CELLS

Chlamydia Also: TB, cancer

- Exophytic mass projecting into the endometrial cavity - clonal overgrowths of endometrium that do not cycle with the rest of it (likely to bleed between cycles) - thick-walled blood vessels - risk of torsion What can these arise as a side effect of ?

Endometrial polyps Tamoxifen (anti-estrogenic on breast BUT pro-estrogenic effects on endometrium)

- Endometrium (glands and stroma) outside the uterus (MC ovary) - Sx: dysmenorrhea, pelvic pain, infertility - Risk of malignant transformation (assoc w/ ovarian ca=endometrioid and clear cell type) - Release pro-inflam factors - PGE-2 incr estrogen locally

Endometriosis - Minor lesions look like powder burns under the serosal surface→ gun powder appearance if involves soft tissue - Large lesions: blood has organized & w/ extensive fibrosis (fallopian tube lesions=scarring→ increases risk of infertility/ectopic pregnancy] note: oral contraceptive pill seems to prevent endometriosis from forming.

-present as “chocolate cysts” →full of old blood

Longstanding endometrial lesion (endometriosis)

-Endometrial tissue extends deep into the wall of the uterus (myometrium)

Adenomyosis

-Common cause of abnormal bleeding and serves as a precursor to endometrial cancer -Toooo....many glands, toooo....little stroma. -Due to too much estrogen (endogenous, exogenous) -Assoc. conditions: obesity (adipose tissue-->estrogen), menopause, PCOS, drugs -Inactivation of the tumor suppressor gene PTEN. -The world health organization, describes two types: Non‐atypical and atypical

Endometrial hyperplasia

Which type of endometrial hyperplasia? - no atypia - crowded glands - decr stroma - dilated glands

Non‐atypical

Which type of endometrial hyperplasia? - atypical nuclei w/ anaplasia - prominent nucleoli - incr mitosis - incr # glands - decr stroma

Atypical

Which type of endometrial carcinoma? -Age: 55‐65 yr -Presents w/: unopposed estrogen, obesity, hypertension, diabetes -Endometrioid morphology -Precursor: Hyperplasia -Genetic abnormalities: PTEN, ARID1A (regulator of chromatin), PIK3CA (PI3K), KRAS, FGF2 (growth factor), MSI *, CTNNB1 (Wnt signaling), TP53 -Behavior: Indolent, spreads via lymphatics

Type I endometrial carcinoma endometrial hyperplasia→ carcinoma→ endometriod appearance (looks like endometrium BUT it is piled up on histo

Which type of endometrial carcinoma? -Age: 65‐75 yr Presents w/: atrophy, thin physique, -Serous, clear cell mixed müllerian tumor morphology -Precursor: serous endometrial intraepithelial carcinoma -Genetic abnormalities: TP53*, aneuploidy, PIK3CA (PI3K), FBXW7 (regulator of MYC, cyclin E), CHD4 (regulator of chromatin), PPP2R1A (PP2A) -Behavior: aggressive, intraperitoneal and lymphatic spread

Type II endometrial carcinoma - sporadic (get it from an atrophic endometrium)→ histo: serous (often has papillary structures) so sometimes call it papillary serous - resembles oviduct. Look for “hobnail cells” and psamomma bodies

- Gross sharply circumscribed firm gray‐white tumors w/ “whorled silk/white whorled masses” - may have areas of degeneration, hemorrhage and calcification. - Benign proliferation of smooth muscle cells arising in myometrium (oval nucleus and long slender bipolar cytoplasmic processes) - more common in blacks - tumors with rearrangements of chromosomes 12q14 and 6p involving the HMGIC and HMGIY genes, respectively

Leiomyomas (fibroids) - MC tumor of women - Related to estrogen exposure→ size increases with pregnancy and decreases with menopause therefore premenopausal women usually

T/F Leiomyomas do not become leiosarcomas

TRUE

- mesenchymal uterine tumors classified between benign leiomyomas and leiomyosarcomas - usually dont metastasize

Smooth muscle tumors of uncertain malignant potential (STUMP)

- bulky, fleshy masses that invade the uterine wall or polypoid masses that project into the uterine lumen - nuclear atypia, mitotic index, and zonal necrosis. - usually single and in older pop - de novo - hemorrhage and necrosis in mass

Leiomyosarcoma * Must distinguish from STUMP. * A subset contains MED12 mutations, a genetic aberration that appears to be virtually unique to uterine smooth muscle tumors.

-arise from the endometrium and contain both malignant glands and malignant mesenchymal elements. -epithelial and stromal components derived from the same founding cell. • Mutations involve the same genes that are mutated in endometrial carcinoma, such as PTEN , TP53, and PIK3CA , while alterations typical of those found in sarcomas are absent

Malignant Mixed Müllerian Tumors note: In addition to bizarre spindle cells, there may be muscle, bone, fat, endometrial stromal sarcoma, and/or cartilage...often a previous history of radiation...aggresive Example: Chondrosarcoma with mixed müllerian cancer Example: Rhabdomyoblasts with mixed müllerian cancer You can stain with myoglobin, and can see cells with z-bands on electron microscopy.

TQ - caused by cancerous cells (mucinous adenocarcinoma) that produce abundant mucin or gelatinous ascites. - Most often from the appendix or ovary

Pseudomyxoma peritonei

-benign condition were leiomyomas are found disseminated in the peritoneal cavity

Disseminated peritoneal leiomyomatosis

Well differentiate papillary mesothelioma vs diffuse malignant mesothelioma?

- Well-diff: low malignant potential | - diffuse: atypia + malig

-Purulent access in distal part of the fallopian tubes and ovaries

``` Suppurative salpingitis (suppurative=purulent=bacterial) ``` Other PID: - Chronic - Tuberculous (SE Asia)

-cysts in the fallopian tubes that arise from embryonic structures (müllerian duct remnants)

``` Hyatids of Morgagni (distal) Paratubal cysts (midportion) ``` Also: - Adenomatoid tumor (assoc w/ mesothelioma) - Primary malignancy

-Graafian follicle remnants that did not regress...possess luteinized theca cell tissue-->hyper-estrogenism

Follicular cysts

- Oversized ovarian cyst filled with blood and fatty debris | - Under estrogen effects

Luteal cyst (corpus luteum cyst)

- hyperplasia and luteinization of the theca cells--> - overproduce androstenedione. - Big & yellow ovaries - Most pts are post-menopausal

stromal hyperthecosis

- Contains both endometrial glands and stroma - Chocolate cyst (hemorrhagic) - Hemoptysis w/ menstrations

``` Endometriotic cysts (of the lung) ``` Can be large cystic masses

- serous - mucinous, endocervical-like and intestinal type - endometrioid - clear cell - transitional cell/Brenner - epithelial-stromal tumors

Epithelial surface-stromal tumors MC and most impt!!

- granulosa tumors - fibromas - fibrothecomas - thecomas - Sertoli-Leydig tumors - Steroid (lipid) cell tumors

Sex-cord stromal tumors

- Teratoma - dysgerminoma - yolk sac tumor - mixed

Germ cell tumors - MC solid tumor of the male - Rare in women except benign teratoma - Worse prognosis in kids and older adults

MC mets to ovary?

Gastric and breast

``` Ovarian tumors: What age group is assoc with each type? -Benign -Borderline -Malignant ```

Benign: young women (20-45 yo) Borderline: slightly older ages Malignant: older women (45-65 yo) + familial cases younger women

What are the the three ovarian components that most tumors of the ovary arise ultimately from ?

- surface/fallopian tube epithelium and endometriosis (MC) - germ cells (migrate to the ovary from the yolk sac, pluripotent, benign cystic teratomas) - stromal cells (sex cords)

- Abdominal pain and distention - urinary and GI symptoms - vaginal bleeding

ovarian tumor

Which type of ovarian tumors are generally considered to be epithelial? What forms do they appear as?

Serous, Mucinous, Endometrioid Benign, borderline, malignant

Which ovarian tumor most often arises in a malignant form?

Serous borderline tumor | MC metastatic tumor of ovary derived form mullerian origin

Which ovarian tumors most often arise bilaterally?

- Serous malignant tumor (MC) - Endometrioid carcinoma - Clear cell carcinoma - Metastatic

- associated with inclusion cysts - may arise from distal fallopian tube - serous type

Serous Tubal Intraepithelial Carcinoma (STIC)

MC type of ovarian malignancy?

serous tumors

- present b/t ages 20-45 yo - tubal-like epithelium - bilateral - incr risk if no children, FH, KRAS mut, TP53 mut) - decr risk if b/t 40-59 yo and hx of oral contraceptives or tubal ligation - may be on ovarian surface or be primary tumors

Serous tumors

- middle adult life - KRAS mutation - unilteral - primary tumors uncommon - ovarian surface rarely involved - form larger multilocular, cystic masses containing gelatinous fluid

Mucinous tumors

-intraperitoneal accum of mucinous material from ovarian or appendiceal tumor

pseudomyxoma peritoneii

If diagnose a young pt with ovarian endometrial cancer, what should you also look out for? note endometrioid tumors have KRAS and TP53 mutations as well

Endometrial carcinoma | Endometrial malignancy of the ovary w/ endometrial ca present earlier than those without concomitant endometrial ca

- lower abdominal pain and abdominal enlargement - GI complaints, frequency/dysuria - Benign forms easily resected - Malignant: progressive weakness, weight loss and cachexia - extend through the capsule to seed the peritoneum, massive ascites (with exfoliated tumor cells or fragments)...peritoneal seeding pattern - Regional nodes frequently involved as well as mets to liver, lungs, GI tract and other sites (NOT breast/bone) - Mets across the midline to the contralateral ovary in @ 50% of cases - Most women with ovarian cancer present with high stage disease/late, therefore poor prognosis - CA-125 useful only to monitor recurrence or progression - Screening of women with BRAC mutations or strong family history is necessary

ovarian epithelial tumors

Germ cell tumor presenting as a cystic mass containing mature well-differiated elements from all 3 germ layers

Mature (Benign) Teratomas AKA CYSTIC TERATOMA

Germ cell tumor presenting as an aggressive mass with immature/embryonic neural tissue (glial tissue)

immature teratoma If malignant, may have SCC or adenoCa inside it..otherwise still aggressive)

- MC in adolescents - Counterpart to seminomas of the testis - Good prog w/ chemo and radiation - Incr LDH, clear cytoplasm w/ central nuclei=fried egg

Dysgerminoma

- Intermediately differentiated aggressive germ cell tumor - AFP - Male infants - Yellow hemorrhagic solid mass - Schiller duval bodies=glomerulus-like structure

Yolk sac tumor (endodermal sinus tumor)

- Rare intermediately differentiated germ cell tumor - emulate chorionic villi so --> - hCG+

Choriocarcinoma

-Poorly differentiated, anaplastic germ cell tumor

Embryonal carcinoma

- derived from ovarian stroma - granulosa and theca cells may secrete estrogens so can be feminizing - Leydig cells secrete androgens so may be masculinizing

Sex Cord-Stromal Tumors

- Fluid associations - basal cell nevus syndrome (multiple basal cells ca-->melanoma) - Meigs syndrome

Fibroma, thecoma, fibrothecoma

Triad of: - ovarian fibroma - ascites - hydrothorax

Meigs syndrome

- Assoc w/ breast dz, endometrial hyperplasia and ca in adults - sexual precocity if pre-adolescent - produces estrogen - behave like low grade malignancies

Granulosa cell tumors

TQ | Common cause of ruptured fallopian tube other than ectopic pregnancy?

Granulosa cell tumor

TQ | Bilateral metastases composed of mucin-producing, signet-ring cancer cells, most often of gastric origin.

Krukenberg tumor

``` A 27 year old female presents with profound lower abdominal pain and fever of 102.4F. Upon PE she has vaginal erythema and a slight purulent cervical discharge. Imaging is most consistent with bilateral tubo-ovarian abscesses. A loculated area under the right diaphragm suggests perihepatitis. Most likely of the following? A) Hydatids of Morgagni B) suppurative salpingitis C) tuberculous salpingitis D) STIC E) hepatitis B ```

B) suppurative salpingitis (purulent, PID) ``` NOT A) peritubal @ fimbriae end, large C) Chronic w/necrotizing granulomas, indolent D) serous ca E) salpingitis not viral! ```

``` A 27 year old female presents with profound lower abdominal pain and fever of 102.4F. Upon PE she has vaginal erythema and a slight purulent cervical discharge. Imaging indicates bilateral tubo-ovarian abscesses. A loculated area under the right diaphragm suggests perihepatitis. Most likely etiology? A) chlamydia B) granuloma inguinale C) gram positive spore former D) gram negative diplococcus E) gram positive diplococcus ```

D) Gonorrhea! NOT A) chlamydia asymp (tubo-lumenal destruction-->infertility) B) fibrosis/strictures C) clostridium (puncture wounds), bacillis anthracis (soil) E) strep pneumo

A 25 year old G0P0 female complains of night sweats and increasingly, excess facial and lower extremity hair. She is muscular with a BMI

D) Stromal hyperthecosis (low change of preg, solid, thecal cells=stromal hypercellulity and luteinization) NOT A) cystic, high BMI (obesity T2DM), follicle cysts w/ serous fluid through stroma B) young, bilat, cystic C) cystic thecal-luteal E) sex cord stromal tumors may not be functional

``` A 47 year old G3P3 presents with pelvic pain and a serosanguinous (serous/bloodY) vaginal discharge. Imaging shows a 9.5cm right ovarian mass. It is multicystic with areas of mural nodularity (wall of cyst thick). Biopsies show tubal-type epithelium arranged in papillae with stratification and anaplasia of invasive epithelial cells. Serum AFP and HCG are negative. Molecular studies indicate TP53+, KRAS-, BRAC1/2-Most likely of the following? A) Primary epithelial lesion of the ovary B) STIC C) Sex cord-stromal tumor D) Metastatic carcinoma E) Malignant teratocarcinoma F) Mucinous cystadenocarcinoma G) Familial serous cystadenofibroma H) Endometrioid cysadenofibroma I) Sporadic serous cystadenocarcinoma ```

I) Sporadic serous cystadenocarcinoma (TP53+, KRAS-) NOT A) Primary epithelial lesion of the ovary B) STIC (not a big mass, not invasive, intrapeithelial) C) Sex cord-stromal tumor (not cystic/large, of epith tumors of ovary) D) Metastatic carcinoma (unliateral, tubal type from breast/GI...mucinous and cell anaplasia...Bilateral!!) E) Malignant teratocarcinoma F) Mucinous cystadenocarcinoma (KRAS +) G) Familial serous cystadenofibroma H) Endometrioid cystadenofibroma (not malig., glands/fibrosis)

Serous tumor vs. mucinous tumor?

Serous=tubal-type epithelium | Mucinous=endocervical/intestinal like epith

Tx of malignant serous cyst?

Bilateral salpingoophorectomies

``` A 35 year old G2P2 female complains of deep pelvic pain, primarily on the right. She is short of breath and states she is unable to work out anymore. She attributes weight gain (approximately 10 lbs in recent weeks) to her now sedentary lifestyle. PE in noteworthy for an abdominal fluid wave. Workup ultimately reveals a left-side, solid ovarian mass measuring 7.2cm in greatest dimension and a right pleural effusion. Ovarian biopsies show fibroblastic proliferation and aggregates of plump cells that are Oil red O positive. Her pleural effusion is most likely A) Chylothorax B) Hemothorax C) Malignant D) Hydrothorax E) Due to alcoholic liver disease ``` ``` What is her ovarian lesion best characterized as? A) Retroperitoneal fibrosis B. Germ cell tumor - embryonal C) Benign solid teratoma D) Sex-cord, stromal tumor E) Dysgerminoma ```

D) Hydrothorax (serous fluid) ``` NOT A) Chylothorax (lipids..thoracic duct) B) Hemothorax (blood) C) Malignant (mets-->pleural effusion) E) Due to alcoholic liver disease (ascites but not thorax) ``` D) Sex-cord, stromal tumor (fibroma-thecoma...meigs syn) NOT A) surrounds ureters B) malig, lung mets and chorios C) cystic

What are some factors in the development of cancer?

- Infection w/ HPV - Obesity (post-meno) - Reproductive hx: estrogen stimulation, timing, and number of pregnancies

T/F nongenetic factors, such as birthdate, can influence the risk of developing a breast cancer

TRUE: For instance, breast cancer risk in females who inherit mutated copies of the BRCA1 or BRCA2 tumor suppressor genes is almost threefold higher for women born after 1940 than for women born before that year, perhaps because of changes in reproductive history.

Why do we have so much breast cancer in modern, industrialized society?

- organ undergoes marked periodic changes during adulthood, particularly during pregnancy, before involuting with age. - old times: puberty-->multiple pregnancy at a young age and didn't live long - now: decr # pregancies, incr age of preg=incr # periods, live longer

The ducts and lobules of the breast have two types of epithelial cells and type types of stroma. What are they?

- epithelial cells: luminal and myoepithelial | - stroma: interlobular and intralobular

Structure of the breast: - 6-10 major duct orifices open onto the skin surface at the nipple - superficial portions are lined by keratinizing squamous cells that change to the double-layered epithelium (luminal and myoepithelial cells) of the remainder of the duct/lobular system. - Successive branching of the large ducts eventually leads to what important unit?

terminal duct lobular unit

supernumary nipples can develop anywhere along the what?

milk line=milk line remnants other development: - axillary breast tissue - congenital nipple inversion

Benign or malignant? | -pain

benign, not malignant

Benign or malignant? | -nipple discharge <60 yo, bilateral

benign worry if unilateral, spontaneous in women >60 yo

Benign or malignant? | -older women with palpable mass

maybe malignant... if bilateral and multiple think benign

abnormal mammogram: | -small irregular clusters

malignant calicfications

- Usually occurs during early lactation - In a non-lactating woman, the usual problem is a pre-existing dermatitis, smoking, and/or a piercing - Usually staph aureus (abscess maker) - Less often, it is strep (spreading cellulitis) - Almost NEVER a sign of cancer

acute mastitis cracks in epith-->infx

- older women w/ erythematous swollen breast - maybe b/l - emboli blocking dermal lymphatics

inflammatory breast carcinoma

- keratin plug--> - ruptured skin due to keratin debris inflam--> - fistula opening at edge of areola

keratinizing squamous metaplasia (lactiferous ducts)

- benign, usually painless lump from trauma-->necrotic fat, giant cells - Necrotic fat cells surrounded by a mixed inflammatory infiltrate, later with calcification, foreign body reaction, scarring

Fat necrosis

- Autoimmune disease that runs with Hashimotos, Type I DM, scleroderma - dense lymphocytic infiltrate around some of the lobules, perhaps with fibrosis; - Can produce HARD LUMPS

Lymphocytic mastopathy (SLL)

- Confined to breast lobules - All these women have been pregnant - autoimmune reaction against the secretory units - r/o TB, sarcoid, fungal, chronic inflam, and a reaction to implant

Granulomatous mastitis

- likely to be tender before menses and after drinking coffee - dilated ducts containing cloudy serous fluid (sometimes bloody or infected) - All breasts during childbearing years contain microscopic form - Gross: blue dome - Surrounding stroma likely to be fibrous - Epithelium may be flattened, cuboidal, columnar, piled up, and/or show apocrine metaplasia. - very pink mitochondrion filled cells resemble real apocrine cell

Cysts | fibrocystic change/nonproliferative

- dense collagenization/stroma distorting and compressing the epithelial structures - most common in upper outer quadrants, patients in 30's - can sometimes see calcium buildup, but means nothing

Fibrosis | fibrocystic change/nonproliferative

- extra, crowded acini in some of the lobules - Calcification is common - can be lactational (during preg) - can be flat epithelial atypia (2 layers)

Adenosis

- more than the usual two layers of cells in ducts and/or lobules. -at least one layer will be myoepithelial cells. - does NOT produce a mass - Between the heaps of cells, you will see cracks and crevices

Epithelial hyperplasia

- proliferation of small ductules and acini in a fibrous stroma (but the basic architecture is intact) - Contains easy to see admixture of myoepithelial cells - CK5/6 stain of a needle biopsy will show you the myoepithelial cells - tender lump in the upper outer quadrant. - Patient is usually around age 30-40. - Presence=3 x future breast CA risk

Sclerosing adenosis

- possess fibrovascular cores, with epithelial hyperplasia-type lesions on the top. Seldom produce masses - myoepithelial cells within the lesion demonstrate it is a papilloma rather than carcinoma in situ. - Risk of breast CA→ these benign lesions are probably caused by mutations of genes other than BRCA1, BRCA2, and p53.

Papilloma

- architectural features suggesting progression toward malignancy - swiss cheese (cribiform) - myoepithelium only on the bottom layer - nuclei run streaming along the glands and the lumen isn’t filled - atypia

-Atypical ductal hyperplasia

- parts of lobules are partially filled with abnormal cells | - atypia

-Atypical lobular hyperplasia

T/F: | carcinoma in situ (lobular and ductal) has a high risk of malignancy and high risk overall

True

Almost all breast malignancies are adenocarcinomas and can be based on the expression of what two genes?

Estrogen Receptor HER2 (ER)-positive, HER2-negative (50% to 65% of tumors) HER2-positive (10% to 20% of tumors, which may either be ER- positive or ER-negative); and ER-negative, HER2-negative (10% to 20% of tumors).

An increase in age is highly associated with which group of breast cancer?

Estrogen receptor positive | HER2 negative

Which form of breast cancer is more common in non-whites (AA, hispanics)

HER- ER- tumors (basal-like...BRAC1) (ER + more common in whites, ER-HER2+ same)

Risk factors for breast cancer: - Germline mutations (BRAC) - 1st degree relatives with breast cancer - Race/ethnicity (AA, hisp. worse) - Age (incr w/ age) - Menarche (age of pub???) - Age at first live birth (before 20 decr risk) - Benign breast disease (prolif w/ atypia incr risk) - Estrogen exposure - Breast density (>60 incr risk) - Radiation exposure (HL pts) - Carcinoma of contralateral breast or endometrium (lobular lesions more b/l) - Diet - Obesity (decr

Puberty before 11 incr risk | After 14 decr risk

What is the single gene mutation assoc? - half of all breast cancers - mutations rare - subtypes of medually and metaplastic) - Poorly differentiated and basal like (triple neg) + p53 mut

BRAC1 (chr 17) familial breast and ovarian

What is the single gene mutation assoc? | -Male breast cancer assoc

BRAC2

What is the single gene mutation assoc? - Triple negative cancer - mutated in sporadic form - half are ER- HER2+

TP53

What is the single gene mutation assoc? | -incr risk of breast cancer after radiation exposure

CHEK2

T/F: | Evidence suggests all breast carcinomas actually arise from cells in the terminal duct lobular unit.

true! ductal=of the breast

- crusty scale on nipple surface - Intraepithelial growth of large, pale, mostly-single cancer cells in the nipple. It looks inflamed - Large cells with clear halo - This is an underlying cancer (DCIS) invading the epidermis. DON’T MISS IT! - Do NOT treat "eczema of the nipple" with cortisone; biopsy it. - Any DCIS extending in the ducts may produce cancerization of lobules (ie: filling the terminal ductules in a lobular unit) - Women may choose mastectomy and breast reconstruction for ductal carcinoma in situ

Paget's disease of the breast | (DCIS, invasive)

- MC DCIS - resembles blackheads on gross exam, and the necrotic cores can be squeezed out. - Central necrosis→ tends to calcify - Sign that this DCIS is likely to turn invasive

Comedocarcinoma (DCIS)

- Fills ducts. - Solid, seen as early microcalcifications - Cells are monomorphic and monotonous

Solid DCIS/non-comedo

- proliferation of tame-looking cells, slightly larger than normal, filling the ductules of one or more lobules. - CADHERIN NEGATIVE - may be bilateral - lobules are expanded but not distorted. - Often there are signet-ring cells - Tend to feature “non-cohesiveness”

LCIS

Firm fibrous, rock hard mass with sharp margins and small, glandular, duct-like cells

Invasive ductal carcionma Special subtypes: - Mucinous/colloid: clumps of cells floating in lakes of mucus, gelatinous - Tubular: single-layer tube, star shaped - Medullary: big, bulky, soft, polygonal cells w/ lymphocytes, HLA-DR - Metaplastic-->SC - Inflammatory-->tumor emboli

ER/HER2? - older women - Mets to bone - low prolif - may include BRAC2 mut - late relapse pattern

ER+, HER2-

ER/HER2? - young women - Mets to bone and brain!

HER2 + | ER-/+

ER/HER2? - triple negative cancer - young women BRAC1 mut, AA, hispanics, - mets to bone and brain - usually short relapse with rare survival when have mets

ER- HER2-

Male breast cancer can metastasize where? | older, superficial and palpable

LLBB

-ulceration of entire breast

Carcinoma en cuirasse

Stages 0-IV (5 stages) of breast cancer....

``` 0=non-invasive 1=breaking through 2=spread to axillary LN 3=spread to sternal LN/chest 4=spread to body ```

- most common benign tumor of the female breast - young women - older women - polyclonal hyperplasias of lobular stroma

Fibroadenoma | intralobular stroma

- much less common than fibroadenomas - usually in older age group (50’s) - range in size from small to huge (“leaflike”) - some can be locally aggressive

Phyllodes tumor | intralobular stroma

Interlobular stroma tumors include fat necrosis, lipoma, fibromatosis Are these benign or malig?

benign malig: angiosarcomas, lymphomas, epidermal/dermal tumors, mets

``` 17 yo white female complains of bilateral nipple discharge and pain in her breasts prior to her period each month. Her menstrual cycle is regular and lasts 5 days each month. Menarche at 12 yo. Dense breasts with slight serous discharge bilaterally and multiple firm nodules bilaterally. PMH is notable for mom who died of breast cancer... Most like which of the following? A) BRAC1 positive B) TP53 positive C) ER- HER2- D) ER + HER2- E) none of the above ```

E! Probably bilaterally fibroadenomas... FH :( but young, b/l, painful, menarche after age 11, multiple nodules all point to :)

Chorionic villi are intended to invade the:

Decidua

Thin placenta. Think:

Intrauterine growth retardation from placental insufficiency

Thick/big placenta. Think: (3)

Diabetes Hydrops fetalis Infection

Big blood clot in placental. Suspect that there was an:

Abruption

A few cotyledons on the placenta that are fibrotic. Think:

Old infarcts

A few cotyledons on the placenta that are overly red:

New infarcts

TQ - Benign hemangioma - no consequence unless it's huge, in which case it acts like a shunt - consumes baby's platelets and can causes CHF - looks like a fleshy, dark, red blob

Chorangioma

- Deep maroon - looks complete - No cotyledons Which surface of the placenta?

Maternal

-membranes are gray, glistening, and translucent, showing the maroon villi through them which surface of the placenta?

fetal

fetal surface of placenta is green in color. think:

meconium | pus (more yellow – chorioamnionitis)

peculiar odor to fetal surface of placenta. think:

Infection. listeria smells sweet, others malodorous

- an accessory lobe that is separated from the main placenta by vasculature - if it overlies cervix → likely to be bleeding

succenturiate lobe

- basal plate (mom's side) is quite a bit bigger than the chorionic plate (baby's side) - will appear as a ring around the edge on the fetal surface - can cause various problems as you'd expect, since the baby's wrapped up inside

circumvallate placenta

- vernix caseosa embedded in the amnion - ERF: granulomatized sloughed baby skin cells - Usually there's oligohydramnios

amnion nodosum

-cord attached to the membrane but away from the placenta.

velamentous insertion

- results from the healing of tiny leaks in the amnion - it is a common cause of miscarriage - can result in damage to body parts in a baby that makes it to term.

amniotic band syndrome

- features a good placenta and membranes but no baby - due to a known or unknown genetic defect -- some of these are triploid and this fades into moles - pathologist will eventually see the villi; unlike hydatidiform mole - trophoblast atrophy rather than proliferation - the edema of the villi isn't impressive

blighted ovum / anembryonic pregnancy

- Child and placenta are enormous - Usually death is due to CHF, most often from severe anemia - problems with the cord cause the child's death

hydrops fetalis

-a twin who died and whose body was flattened by the other child's

fetus papyraceous

baby calcifies in utero

lithopedion

- Most often in ampulla of fallopian tube - suspect with hx of amenorrhea, lower-than-expected rise in hCG based on dates, and sudden lower abdom pain - confirm with U/S - often mistaken for appendicitis risk factors: - hx of infertility - salpingitis (PID) - ruptured appendix - prior tubal surgery

ectopic pregnancy

-Premature separation of placenta from uterine wall before delivery of infant Risk factors: -trauma (motor vehicle accident), smoking, HTN, preeclampsia, cocaine abuse - abrupt, painful bleeding in 3rd trimester - possible DIC, maternal shock, fetal distress - Life threatening for mother and fetus

Placental abruption

Defective decidual layer -> abnormal attachment and separation after delivery Risk factors: - prior C-section (old scar*) - inflammation - placenta previa describe each of the three types: - placenta accreta - placenta increta - placenta percreta

placenta Accreta – placenta Attaches to myometrium without penetrating it; MC type placenta INcreta – placenta penetrates INto myometrium placenta PERcreta – placenta penetrates ("PERforates") through myopetrium and into uterine serosa (invades entire uterine wall); can result in placental attachment to rectum or bladder

attachment of placents to lower uterine segment over (or < 2 cm from) internal cervical os risk factors: - multiparity - prior C-section assoc with painless 3rd trimester bleeding.

placenta previa

one chorion = ? | two chorions = ?

one chorion = monozygotic | two chorions = dizygotic

-Caused by a “one way valve in the placenta” [ie one-way channel between the twins' umbilical cords] ONE BIG TWIN AND ONE SMALL TWIN - The twin who gets the blood will be big and can die of circulatory overload. - The twin who loses the blood will be small and can die of anemia.

Chronic twin-twin transfusion syndrome

amnion on both sides, chorion in the middle, so it must be:

dichorionic

- very malformed fetus with no heart | - go to term bc the healthy twin provides blood and beating hear

Acardius

-new-onset HTN with either proteinuria or end-organ dysfxn after 20th week of gestation ( endothelial dysfxn*, vasoconstriction, ischemia presents as: - BP ≥ 140/90 - > 300 mg/day proteinuria - edema

preeclampsia | may also have to do with lack of tolerance to dad's antigens

preeclampsia + maternal seizures = ?

eclampsia

vascular changes of eclampsia:

fibrinoids and clear fatty "atherosis"

where is the necrosis located in the liver in eclampsia?

periportal necrosis

- presence of excess fluid in two or more fetal body parts, thorax, abdomen, skin - causes heart failure, profound anemia, hypoxia, extramedullary hematopoiesis, liver dysfxn - immune causes: erythroblastosis fetalis – hemolytic anemia due to maternal antibodies

hydrops fetalis

- large placenta - macrosomia - congenital malformations - increased risk of thrombosis - due to increased levels of maternal blood

gestational diabetes

- triploid (69,XXX/XXY/XYY) - 2 sperm + 1 egg - slight increase in hCG - contains fetal parts - sx: vaginal bleeding, abdominal pain - unevenly swollen villi

partial mole

- diploid (46,XX/XY) - marked increase in hCG - increased uterine size - 2% convert to choriocarcinoma - NO fetal parts - enucleated egg + single sperm (subsequently duplicated paternal DNA – "daddy's girl") - 15-20% malignant trophoblastic dz - sx: 1st trimester bleeding, enlarged uterus, hyperemesis, pre-eclampsia, hyperthyroidism - imaging: "honeycombed" uterus or "clusters of grapes," "snowstorm" on U/S - uniformly swollen villi

complete mole

- hypertrophic trophoblast with at least some villi, penetrating deep into, and maybe through, the uterine and/or vaginal walls, following a hydatidiform mole - Villi may embolize to the lungs but not truly metastasize

invasive mole

- rare; can develop during or after pregnancy in mother or baby - malignancy of trophoblastic tissue (cytotrophoblasts, syncytiotrophoblasts - NO chorionic villi present - increased frequency of bilateral/multiple theca-lutein cysts - presents with abnormal increased hCG, shortness of breath, hemoptysis - hematogenous spread to the lungs - responsive to chemo

choriocarcinoma

TQ protein malnutrition resulting in: -skin lesions (flaking rash similar to pellagra, no niacin made from tryptophan) -edema (due to decreased plasma oncotic pressure – hypoalbuminemia) -liver malfunction (fatty change due to decreased apolipoprotein synthesis) -small child with swollen abdomen -"flag sign" (without tyrosine to make melanin, the hair cannot pigment) – ERF "MEALS" acronym: - Malnutrition - Edema - Anemia - Liver malfunction - Skin lesions

Kwashiokor

total calorie malnutrition resulting in: - tissue and muscle wasting - loss of subcutaneous fat - variable edema

Marasmus - anorexia nervosa - child abuse / neglect (USA) - prisoners

- pain, paresthesias, blind spots, blindness... | - undernutrition + tobacco + something else

Strachen syndrome / Cuban epidemic neuropathy

TQ - night blindness*** - dry, scaly skin (xerosis cutis)* - corneal degeneration (keratomalacia)* - Bitot spots on conjunctiva* - Squamous metaplasia of the eye's normal lubricant glands -> xerophthalmia (dry eyes) - immunosuppression

Vitamin A deficiency

TQ - rickets in children - osteomalacia in adults - hypocalcemic tetany - high PTH - frayed costochondral junctions seen on x-rays – ERF - seen in exclusively breastfed infants - exacerbated by low sun exposure, pigmented skin, prematurity - veiling of women

Vitamin D deficiency

TQ - hemolytic anemia - acantholysis - muscle weakness - posterior column and spinocerebellar tract demyelination

Vitamin E deficiency | aka tocopherol / tocotrienol

TQ - neonatal hemorrhage with increased PT and increased aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize this vitamin) - can also occur after prolonged used of antibiotics - preemies, "only milk" babies, fat malabsorption, liver failure, Coumadin Rx – ERF -complication = brain hemorrhage in babies

Vitamin K deficiency (vitamin K allows gamma-carboxylation of glutamic acid to make clotting factors II, VII, IX, X, C, and S) "CS 1972"

TQ Deficiency results in impaired glucose breakdown -> ATP depletion worsened by glucose infusion; highly aerobic tissues (e.g., brain and heart) affected first -causes Wernicke-Korsakoff syndrome and berberi -seen in malnutrition and alcoholism -dx made by increase in RBC transketolase activity following the deficient vitamin's administration Wernicke-Korsakoff syndrome: - confusion, ophthalmoplegia, ataxia (classic triad) + confabulation, personality change, memory loss (permanent) - damage to medial dorsal nucleus of thalamus and mammillary bodies Wet beriberi: - high-output cardiac failure (dilated cardiomyopathy) - edema Dry beriberi: - polyneuritis - symmetrical muscle wasting

Vitamin B1 deficiency (aka thiamine) Think "ATP": - a-ketoglutarate dehydrogenase - Transketolase - Pyruvate dehydrogenase "Ber1Ber1"

TQ - Cheilosis*** (inflammation of lips, scaling and fissures at the corners of the mouth) - Corneal vascularization** - Glossitis*** - first problem is impaired intestinal absorption of iron – ERF

Vitamin B2 deficiency (aka riboflavin) "2 C's"

TQ - glossitis - pellagra – can be caused by Hartnup dz (decreased tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism), and isoniazid (decreased vitamin B6) pellagra (3 D's): - Diarrhea - Dementia (also hallucinations) - Dermatitis (C3/C4 dermatome "broad collar" rash, hyperpigmentation of sun-exposed areas)

Vitamin B3 deficiency | aka niacin

- dermatitis - enteritis - alopecia - adrenal insufficiency - painful paresthesias in the lower legs ("burning feet") – ERF - needed to make CoA! – ERF

Vitamin B5 deficiency | aka pantothenic acid

- convulsions - hyperirritability - peripheral neuropathy** (deficiency inducible by isoniazid and oral contraceptives) - sideroblastic anemias due to impaired synthesis and iron excess -"may simply cause elevated homocysteine levels (like folate or B12 deficiency)"

Vitamin B6 deficiency | aka pyridoxine

TQ - macrocytic, megaloblastic anemia - hypersegmented PMNs - glossitis - NO neurologic symptoms (as opposed to B12 deficiency) - increased homocysteine levels - normal methylmalonic acid levels - neural tube defects** / cleft palate - MC vitamin B12 deficiency in the USA - seen in alcoholism and pregnancy - "phenytoin users" – ERF

Vitamin B9 deficiency | aka folate

TQ - macrocytic, megaloblastic anemia - hypersegmented PMNs - paresthesias** and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin - associated with increased serum homocysteine and methylmalonic acid levels - prolonged deficiency -> irreversible nerve damage - pernicious anemia due to anti-intrinsic factor antibodies

Vitamin B12 deficiency | aka cobalamin

- exfoliative dermatitis - alopecia - enteritis caused by antibiotic use or excessive ingestion of raw egg whites.

Vitamin B7 deficiency | aka biotin

``` TQ Scurvy -swollen gums** -bruising* -petechiae around hair follicles*** -hemarthrosis -anemia -poor wound healing** -perifollicular and subperiosteal hemorrhages*** -"corkscrew hair" ``` -weakened immune response

Vitamin C deficiency (aka ascorbic acid) -Collagen synthesis defect

TQ - hypochromic, microcytic anemia - koilonychia - cracks at side of mouth

iron deficiency

TQ - delayed wound healing** - hypogonadism - decreased adult hair - dysgeusia (distorted taste) - anosmia - acrodermatitis enteropathica** (well-demarcated, scaly plaques in intertriginous areas – dermatitis around the mouth and anus) - may predispose to alcoholic cirrhosis Triad: - alopecia - dermatitis - diarrhea

Zinc deficiency | acrodermatitis enteropathica – AR inability to take up zinc [SLC39A4]

Deficiency known in preemies, starvation, old protocols for total parenteral nutrition, zinc enthusiasts. Anemia, bony deformities (if longstanding in kids), and depigmentation.

Copper deficiency

TQ - China's Kashen dz - Central Asia's "Kashin-Beck" dz - Deficiency within soil - makes hearts more vulnerable to Coxsackievirus *** - Mutilates growing bones and joints

Selenium deficiency

TQ - pot-bellied - pale - puffy-faced child - protruding umbilicus - protuberant tongue - poor brain development

Iodine deficiency -> cretinism | "6 P's"