Pathology - Phase C

Lichen sclerosis: leukoplakia with parchment paper like skin (thin epidermis), some Cancer risk

Lichen simplex chronicus: leukoplakia with thich leathery skin (epithelial hyperplasia). no Ca risk. Just think "simple is better"

• condylomata lata (syphilis)
• condylomata accuminata (HPV, koilocytic cells)

HPV 16,18 progress to VIN

longstanding lichen sclerosis progresses to SCC

koilocytic cells (raisin nuclei), peri-nuclear halo

Usual: Entire epithelium is VIN III, irreversiible is carcinoma in situ (not reversible), seen in young women with HPV, poorly differentiated SCC

Differentiated: potential for a very rapid cancer usually associated with lichen sclerosis and appears in postmenopausal women, well differentiated SCC

• -red, itchy, crusty lesions
• -you will think it is eczema, but if it sticks around for 2+/52, it is important to biopsy
• -mammary always has an underlying carcinoma while the vulvar variety rarely has an underlying ca.

Melanoma is S100 positive, important to do so because it is an aggressive cancer. Prognosis is dependent on the depth of the invasion

• lichen sclerosis
• lichen simplex chronicus
• vulvar carcinoma
• vitiligo
• benign dermatosis (psoriasis, etc)

• Candidiasis
• Trichomaniasis
• Bacterial Vaginosis

Vaginal adenosis: clear-cell carcinoma, intrauterine exposure to DES, due to persistence of columnar epithelium in upper 1/3 of vagina

Sarcoma botroyides (ebryonal rhabdosarcoma): peds tumor, grape-like mass hanging out of vagina (is a skeletal muscle tumor)

BRCA1

• -Usually gonococcal infection
• -acute phase: fever, abdo pain, tubo-ovarian abscess
• -Chronic phase: scarring with tubal obstruction, sterility, tubal pregnancies

1) oviduct obstructions (PID, endometriosis, tumors)

2) chorionic villi

benign: adenomatoid tumor 

BRCA1: papillary serous carcinoma of FT

ascending: most common, usually mycoplasm or candida, associated with PROM

Hematogenous: TORCHES, listeriosis

1%

• Hydatiform mole (complete or incomplete)
• Invasive mole
• Choriocarcinoma

Progressively higher titres as you go down the list. More likely to be cancer as you go down (last one is)

• - no fetal heart sounds
• - grape-like structures (the edematous villi) passing through the os
• - "snow storm" on U/S

Complete: 2 sperm in an empty egg (46 chrom), all chorionic villi are abnormal, 2-3% cancer risk, most common gestational trophoblastic disease

Incomplete: 2 sperm in viable egg (69 chrom), contains fetal parts, some normal chorionic villi

• -more locally invasive complete moles
• -harder to remove by D&C, track with hCG
• -may embolize and head to different organs like a metasteses

• -very aggresive malignant tumor
• -can arise in 2 ways: germ cell tumor, or as a complication of gestation
• -Presents as a bloody, brownish discharge with higher B-hCG titres even than a complete mole
• -Have usually metastisized by the time they are detected

• -CC has hemorrhagic, necrotic masses
• -THERE ARE NO CHORIONIC VILLI IN CC, BUT THERE ARE IN MOLES

Gestation: responds well to chemo (probably due to paternal antigens acting as an adjunct to chemo)

Gonad: very poor response to chemo

Trophoblastic tumors do not give off elevated levels of B-hCG

Instead they give off high levels of placental lactogen

• Pre-eclampsia: HTN, proteinuria, and edema in the 3rd trimester, starts in 24-25th weeks
• Eclampisa: Pre-eclampsia + seizures
• HELLP: Pre-eclampsia + thrombotic microangiopathy involving liver

DIC

• -higher number  of infarcts
• -acute arthrosis of the placental arteries

renal necrosis

• -benign prolif of SM arising from myometrium due to estrogen and progesterone
• -pre-menopausal women with no kids prototypically
• -usually asymptomatic, but can present with AUB, infert, pelvic mass
• -multiple lesions with white whorls

• -present with AUB
• -may progress to cancer (<2% in premeno, <6-7% in postmeno)
• -contain thick-walled BVs

• -Basically divurticuli of endometrial tissue into the myometrium
• -It is the basalis layer that invades

GnRH analogs, block the effects of progesterone

• -endometrial glands AND stroma outside of the uterus
• -dysmenorrhea, pelvic pain, and sometimes infertility
• -usually in 20-30 year olds
• -most common site is the ovariy (chocolate cyst)
• -When not on the ovary look for blue and red "power burn" lesions

• 1) retrograde menstruation: menstrual stuff going the wrong way, most accepted theory
• 2) Celomic metaplasia: diff of mesothelial cells into endometrium-like tissue
• 3) lymphatic spread

• -genes
• -acquired properties of the endometrium
• -poor immune clearance.

• 1) The foci themselves (main source)
• 2) Ovary
• 3) skin and fat

• -Endometrioid ca
• -clear cell carcinoma (super aggressive)

no

adenomyosis is the basalis layer, which does not respond to hormones and that is why there is not bleeding

endometriosis is the functional layer, which is why you see all the sx

Bleeding resulting from proliferative endometrium as a result of anovulation or abnormality of follicle development in the absence of any organic disease.

• Causes
• -Chronic anovulation: peri menarchal, perimenopausal
• -unopposed estrogen (endometrial hyperplasia)

• -caused by unopposed estrogen
• -usually in (peri)menopausal women
• -usually preceeds endometrial adenocarcinoma (most cases do not progress though)
• -high gland to stroma ratio (3:1)

• Need 2/3 of the following:
• -endometrial glands
• -endometrial stroma
• -hemerosiden laden microphages

ovarian dysfunction

• -Type 1: endometriod
•   -arises from endometrial hyperplasia
•   -more common of the two (80%)
•   -good prognosis (90% 5 yr survival)
•   -usually in 50-60 year olds
• -Type 2: Papillary serous
•   -aggresive
•   -p53 mutation
•   -70+ years old (due to atrophy)
•   -Metastisize easily

they produce proteins E6 and E7 which knock out p53 and Rb proteins which usually act as a check in the cell cycle.

• -in both you see nuclear enlargement and atypia
• LSIL: 
•  -CIN I
•  -LOWER 1/3 of epidermis only
•  -30% persist, 10% progress
• HSIL
•  -CIN II and III
•  -2/3 to full thickness involvement
•  -60% persist, 10% progress
•   -CIN III is more associated with invasive cancer

• Stage 0: HSIL/CINIII
• Stage I: limited to cervix
• Stage II: limited to upper 1/3 of vagina
• Stage III: has extended to lower vagina
• Stage IV: has extended beyond true pelvis

• need 2/3 of:
• 1) oligo or anovulation
• 2) clincal or biochemical signs of hyperandrogenism
• 3) PC ovaries on U/S and exclusion of other causes.

• We don't really know, but a good way to remember is:
• 1) There is increased LH (for some reason that we dont know the GnRH pulsatility is increased)
• 2) Increased LH decreases FSH causing LH:FSH >2
• 3) Increased LH causes increased androgen production by the thecal cells
• 4) adipose tissue converts androgen to estrone which will further decrease the FSH
• 5) decreased FSH causes granulosa cells to decrease estrogen production which causes follicular degeneration

NOT useful for screening! IS useful for tracking treatment efficacy and if the disease returns.

• -super treatable if it is caught early (90% survival), but only 24% are caught early.
• -4th leading cause of  cancer death in women
• -difficult to diagnose until pressure sx start

because they have a propensity to seed the peritoneal cavity

• -Have both epithelial and stromal tumors
• -stromal components may be cartilagenous or SM-like

mets, usually from the lungs

Waterhouse-Friedriechsen syndrome due to meningococcal sepsis. 

If on long term steroids, the adrenals atrophy and withdrawing steroids or times of increased demand (e.g. after surg) will result in acute adrenal insufficiency

neuroblastoma (most common extracranial solid tumor in kids). Usually presents as an enlarging abdominal mass

craniopharyngioma

• You see:
• -Lymphocytic infiltration
• -atrophy of thyroid follicles
• -Hurthle cells (cells with abundant pink granular cytoplasm)

Do FNA because these people are at 80x more risk for B-cell lymphoma

Subacute granulomatous (DeQuervains) thyroiditis

Some problem with making thryroid hormone (e.g. decreased iodine intake) cause increased TSH which causes some areas to enlarge (differential response to TSH)

NOPE

• 1) Papillary thyroid (75-85%)
• 2) Follicular carcinoma (10-20%)
• 3) Medullary ca (5% of ca)
• 4) anaplastic (rare, usually old people)

• 1) Densities (DCIS)
• 2) archetectual distortion (LC)
• 3) calcifications (DCIS)
• 4) changes over time

• 1) gender (99% female)
• 2) age (steady rise after menopause)
• 3) geographic influence
• 4) estrogen exposure

Major RF's are hormonal and genetic!

They are often triple negative tumors (no ER, PR, or HER2/neu)

These are BAD and HIGH GRADE tumors. Can often express pus from them.

Mammary pagets. Always an underlying DCIS

LCIS has lost e-cadherin. Do a stain!

Whether or not there are LN mets

• 1) LN mets (most important)/other mets
• 2) invasive vs in situ disease
• 3) tumor size

In hyperplasia, all 4 glands are enlarged. Only one or 2 in adenoma/carcinoma

Invasion of an area it shouldn't be. There is no other way, these tumors are boring.

primary - high calcium and low phosphate

secondary (usually renal failure) - kidney can no longer excrete phosphate causing a high phosphate level, which LOVES to bind to free calcium, causing a low/normal Ca++ level with elevated PTH as the parathyroid tries to compensate!

sporadic adenomas or hyperplasia (95%)

only 5% are due to familial MEN syndromes

• 1) usually asymp
• if there are symptoms, general hypercalcemia sx:
• -moans (peptic ulcer pain, Ca++ causes increased gastrin production)
• -bones (pain, osteitis fibrosa cystica)
• -stones (kidney stones)
• -psychiatric overtones (depression, seizures)

90% are primary hyperparathyroidism

tetany (neuromuscular irritability)

• PHP: calcium up, PTH up
• SHP: calcium N/low, PTH up
• Hypercalcemia of malig: calcium up, PTH down
• hypopara: ca down, PTH down

hypoglycemia

• -Pituitary adenomas
• -Parathyroid hyperplasia
• -Pancreatic endocrine tumores (ZES, insulinoma, etc)

• 1) MEN 2A (Sipple synd) (95% of MEN 2)
• 2) MEN 2B (william synd)
• 3) Familial medullary thyroid cancer

All are a mutation of the RET oncogene. If someone has this mutation in the GERMLINE, do a prophylactic thyroidectomy (all involve medullary thyroid ca)

• 1) Thyroid medullary ca by age 20 100% of the time
• 2) Pheo
• 3) Parathyroid hyperplasia

• 1) Pheo
• 2) Thyroid medullary ca
• 3) mucocutaneous ganglioneuromas
• 4) Marfanoid habitus (Abe Lincoln)

NO HYPERPARATHYROID!! Develops 10 years earlier than MEN 2A

neuroendocrine granules