Embryo/Repro Flashcards
What is seen with a mutation in the Sonic Hedgehog gene?
Holoprosencephaly
What is the function of the Wnt-7 gene?
Ventral-dorsal axis organization
What is the function of the FGF gene?
Found at apical ectodermal ridge (tip of limb). Stimulates mitosis of underlying mesoderm –> lengthening of limbs
What is the seen with mutation of the Homeobox genes?
Hox genes orient the embryo in the cranial-caudal direction. Mutations cause limbs in the wrong places.
When is a fetus most susceptible to teratogens?
Weeks 3-8
This is the embryonic period & is when most organs are formed.
When does gastrulation occur?
3 layers = Week 3 (trilaminar)
When during embryogenesis are the limbs formed?
4 limbs = Week 4
When can the sex of a baby be determined by US?
Week 10
When does the neural tube form during embryogenesis?
Weeks 3-4
What structures are formed from the neural crest?
PNS neurons Schwann cells Melanocytes Parafollicular thyroid cells Pia & arachnoid Bones of the skull Aorticopulmonary septum
What are the mesodermal defects?
CV LATER:
Cardiac defects Vertebral defects Limb defects Anal atresia Tracheo-Esophageal fistula Renal defects
What structures are formed from the endoderm?
Lungs Gut tube epithelium Liver Gallbladder Pancreas Thymus Thyroid follicular cells Parathyroid
What is the difference between agenesis & aplasia?
Agenesis = absent primordial tissue
Aplasia = Primordial tissue was present but organ is absent
What is the difference between Deformation & Malformation?
Malformation = intrinsic & occurred during embryogenesis
Deformation = Extrinsic & occurred after embryogenesis
What is the embryologic effect of ACE inhibitors?
Renal damage
What is the embryologic effect of alkylating agents?
Absence of digits & other anomalies
What is the embryologic effect of aminoglycosides?
CNVIII toxicity
Just like how they are ototoxic in adults
What is the embryologic effect of Lithium?
Ebstein’s anomaly
Ebstein’s = Atrialized RV = most of the right heart is atrium
What is the embryologic effect of phenytoin?
Fetal hydantoin syndrome:
Microcephaly Dysmorphic craniofacial features Hypoplastic distal phalanges & nails Mental retardation Cardiac defects Intrauterine growth restriction
What is the embryologic effect of Tetracyclines?
Discolored teeth
What is the embryologic effect of thalidomide?
“Flipper” limb defects
ThaLIMBdomide
What is the embryologic effect of Valproic acid?
Inhibits maternal folate absorption –> neural tube defects
What is the embryologic effect of warfarin?
Bone deformities
Fetal hemorrhage
Ocular abnormalities
Use heparin during pregnancy
What is seen with cocaine use during pregnancy?
Abruptio placentae
Abnormal fetal development
Fetal addiction
What is seen with smoking during pregnancy?
Premature delivery
IUGR
ADHD
What can be seen in infants born to diabetic mothers?
Caudal regression syndrome (aka sacral agenesis; ranges from anal atresia to full blown sirenomelia)
Congenital heart defects
Neural tube defects
NRDS
When must separation occur to cause the various types of monozygotic twins?
dichorionic, diamniotic
4-8 days (morula) –> Monochorionic diamniotic
8-12 days (blastocyst) –> Mono-mono
> 13 days –> mono-mono & conjoined
What are the chorionic villi composed of?
Which cell type secretes hCG?
Cytotrophoblasts (inner layer)
Sincytiotrophoblasts (outer layer) - secrete hCG
What is the urachus?
What pathology is seen with it?
Allantois –> Urachus –> Median umbilical fold
Urachus is a duct between the bladder & yolk sack
1) Patent urachus –> Urine discharge from umbilicus
2) Vesiurachal diverticulum –> outpouching of bladder
3) Adenocarcinoma of the bladder
What is the Vitelline duct?
What pathology is seen with it?
It connects the yolk sac to the midgut lumen
1) Meckel’s diverticulum
2) Vitelline fistula –> meconium discharge from umbilicus
What is derived from the 1st aortic arch?
Maxillary artery
MS CARD
What is derived from the 2nd aortic arch?
Stapedial artery & hyoid artery
MS CARD
What is derived from the 3rd aortic arch?
Common Carotid & part of internal Carotid
MS CARD
What is derived from the 4th aortic arch?
Aortic arch & proximal R. subclavian
MS CARD
What is derived from the 5th aortic arch
Nothing (regresses)
MS CARD
What is derived from the 6th aortic arch?
Ductus arteriosus & proximal pulmonary artery
MS CARD
What types of tissue is the branchial (pharyngial) apparatus composed of?
Clefts - Ectoderm
Arches - Mesoderm
Pouches - Endoderm
What do the branchial clefts develop into?
1st cleft –> EAM
All others are obliterated. If one is not –> branchial cleft cyst within lateral neck
What is derived from the 1st pharyngeal (branchial) arch?
Meckel's cartilage Mandible Malleus & incus Mandibular ligament Muscles of mastication Mylohyoid
Anterior belly of the digastric
Tensor tympani
Tensor veli palatini
The nerves required to chew (V2 & V3)
What is seen with failure of the 1st aortic arch to develop properly?
Neural crest fails to migrate –> Treacher Collins syndrome
Symptoms:
Mandibular hypoplasia
Facial abnormalities
What is derived from the 2nd pharyngeal (branchial) arch?
Stapes Styloid leSSer horn of hyoid Stapedius muscle Stylohyoid muscle poSterior belly of the digastric
Seventh cranial nerve (CNVII)
What is derived from the 3rd pharyngeal (branchial) arch?
GlossoPHARYNGEAL nerve (CNIX)
Greater horn of hyoid
styloPHARYNGEOUS
What causes a congenital pharyngocutaneous fistula?
Persistent 3rd branchial cleft & pouch –> fistula to lateral neck
What is derived from the 4th pharyngeal (branchial) arch?
think swallowing
Superior laryngeal nerve (CNX) Thyroid cartilage Pharyngeal constrictor muscles Cricothyroid muscle Levator veli palatini muscle
What is derived from the 6th pharyngeal (branchial) arch?
think talking
Recurrent laryngeal nerve (CNX)
All laryngeal cartilages except thyroid cartilage (4th)
All intrinsic laryngeal muscles except cricothyroid
What is derived from the 1st branchial (pharyngeal) pouch?
Middle ear cavity
Mastoid air cells
Endoderm-lined structures of ear
Ear, Tonsils, bottom-To-top
What is derived from the 2nd branchial (pharyngeal) pouch?
Palatine tonsil epithelium
Ear, Tonsils, bottom-To-top
What is derived from the 3rd branchial (pharyngeal) pouch?
dorsal –> inferior parathyroids (bottom)
ventral –> thymus (to)
Ear, Tonsils, bottom-To-top
What is derived form the 4th branchial (pharyngeal) pouch?
Superior parathyroids (top)
Ear, Tonsils, bottom-To-top
What causes a cleft lip?
Maxillary & medial nasal processes do not fuse
What gene causes male development?
SRY gene –> Testis determining factor
What is derived from the mesonephric duct?
aka Wolffian duct –> SEED
Seminal vesicles
Epididymis
Ejaculatory duct
Ductus deferens
What is seen with congenital 5-alpha reductase deficiency?
Male internal genitalia
Ambiguous external genitalia until puberty
(DHT necessary)
What causes hypospadias?
Failure of urethral folds to close
What causes epispadias?
Faulty positioning of the genital tubercle
What is the lymphatic drainage of the vagina?
Proximal 2/3 –> obturator, external iliac, hypogastric nodes
Distal 1/3 –> superficial inguinal nodes
What ligament contains the ovarian vessels?
What does the ligament connect?
Suspensory ligament
Anchors ovaries to the lateral pelvic wall
What ligament contains the uterine vessels?
What does the ligament connect?
Cardinal ligament
Anchors the cervix to side wall of the pelvis
What ligament contains the Artery of Sampson?
What does the ligament connect?
Round ligament
Uterine fundus –> Labia majora
What ligament in the female pelvis travels through the inguinal canal?
Round ligament
Uterine fundus –> labia majora
What are the components of the broad ligament?
Mesometrium (lower portion)
Mesosalpinx (upper portion)
Mesovarium (lies on ovary)
What is connected by the ligament of the ovary?
Connects the ovary to the uterus
What is the pathway of sperm to exit the male?
SEVEN UP: Seminiferoustubules Epididymis Vas deferens Ejactulatory duct (Nothing) Urethra Penis
What nerves are responsible for the male sexual response?
Erection - pelvic nerve (parasympathetic)
Emission - hypogastric nerve (sympathetic)
Ejaculation - pudendal nerve
What is secreted by Sertoli cells?
Embryogenesis - Mullerian inhibitory factor
Adult:
Inhibin - feedback inhibition to FSH
Androgen binding protein - keep local [T] high
What forms the blood-testis barrier?
Tight junctions between Sertoli cells
How does increased temperature affect the testis?
Decreased sperm production
Decreased inhibin production
Normal testosterone production
What are the stages of sperm development?
What is their ploidy?
1) Spermatogonium (2n, 2c)
2) Primary spermatocyte (2n, 4c)
3) Secondary spermatocyte (1n, 2c)
4) Spermatid (1n, 1c)
5) Spermatozoa
What is spermatogenesis?
Spermiogenesis?
Spermatogenesis is the whole process
Spermiogenesis is spermatid –> mature spermatozoon
Where is aromatase found in adult males?
Leydig cells
Adipocytes
What is the relative potency of endogenous estrogens?
Where are they produced?
Estradiol > Estrone > Estriol
E2 = ovary E1 = adipose E3 = placenta
What is the effect of estrogen on lipoprotein levels?
^HDL
Decreased LDL
Describe Estrogen production in the ovary
LH stimulates theca cells –> Cholesterol –> Androstenedione via Desmolase
FSH stimulates granulosa cells –> Androstenedione –> Estrogen via Aromatase
How much estrogen is in a pregnant woman?
50x normal E2 & E1
1000x normal E3
What are the functions of progesterone?
Stimulate endometrium (glands & spiral arteries) Maintain pregnancy Decrease myometrial excitability Production of thick cervical mucus (inhibits sperm entry) Increases body temperature Inhibits gonadotropins Relaxes uterine smooth muscle Decreases estrogen receptor density
What are the Tanner stages of development?
I) Childhood
II) Pubic hair; breast bud
III) Pubic hair darkens & is curly; ^Penis length; ^Breast size
IV) ^Penis width; dark scrotal skin; raised areolae
V) Adult; areolae are not raised
What phase of the menstrual cycle varies from woman to woman?
The follicular phase varies
The luteal phase 14 days in all women.
Thus, ovulation + 14 days = menstruation
What is a normal menstrual cycle length?
21-35 days
35 = oligomenorrhea
What is menorrhagia?
Metrorrhagia?
Menorrhagia - heavy or prolonged bleeding
Metrorrhagia - irregular menstruation
Why is body temperature a marker for ovulation?
Ovulation –> corpus luteum releases progesterone –> ^temp
What is Mittelschmerz?
Rupture of a follicle –> small bleed into peritoneum –> irritation that can mimic appendicitis
When do oocytes undergo meiosis I & II?
Begin in utero
Arrested in prOphase of meiosis I until ovulation
Arrested in METaphase II until fertilization (it MET a sperm)
What are the stages of ovum development & their ploidy?
Oogonium (2n, 2c)
Primary oocyte (2n, 4c)
Secondary oocyte (1n, 2c)
Ovum (1n, 1c)
What is hCG detectable?
In blood at 1 week In urine (home test) at 2 weeks
When does hCG peak during pregnancy?
What secretes it?
Week 10
It is secreted by syncytiotrophoblasts
When does implantation of an embryo occur?
6 days after fertilization
What is the function of prolactin?
Oxytocin?
Prolactin - Induces/maintains lactation & inhibits GnRH
Oxytocin - Milk letdown & causes uterine contractions
Where is progresterone synthesized from during pregnancy?
1st trimester = corpus luteum (maintained by hCG)
2nd & 3rd trimesters = placenta
What causes Klinefelter’s syndrome?
What is seen?
XXY genotype
Testicular atrophy Long extremities Gynecomastia Female hair distribution Barr body (inactivated X chromosome in nucleus) ^FSH, ^LH, ^Estrogen, low Testosterone
Common cause of hypogonadism seen during an infertility workup.
What causes Turner syndrome?
What is seen?
XO genotype
Short stature Streak ovaries Shield chest w/ wide nipples Bicuspid aortic valve Preductal coarctation of the aorta Horseshoe kidney Cystic hygroma (webbed neck) Lymphedema in hands/feet Dysgerminoma Short 4th digit
Most common cause of primary amenorrhea
What is the genetic cause of Turner syndrome (precisely)?
60% = complete monosomy 30% = mosaicism 10% = structural abnormality of X chromosome
What is seen in double Y males?
XYY genotype
Tall
Severe acne
Antisocial behavior
Autism spectrum disorders
What causes female pseudohermaphroditism?
Ovaries present (XX) but external genitalia are virilized or ambiguous
Caused by inappropriate exposure to androgens during early gestation
What causes male pseudohermaphroditism?
Testes present (XY) but external genitalia are female or ambiguous
Most common cause if androgen insensitivity syndrome
What is seen with true hermaphroditism?
46XX or 47XXY
Both ovary and testicular tissue present. Ambiguous genitalia. This is very rare.
What causes androgen insensitivity syndrome?
What is seen?
X-linked defect in the androgen receptor (46XY)
Female appearance Vagina ends in blind pouch No sexual hair Testes present inside (removed to prevent malignancy) ^Testosterone, ^Estrogen, ^LH
What is seen in 5-alpha reductase deficiency?
Autosomal recessive inheritance
Ambiguous genitalia until puberty (^T causes masculinization)
Everything else is normal (hormone levels, internal genitalia)
What causes Kallmann syndrome?
What is seen?
Defective migration of GnRH cells & formation of olfactory bulb
Lack of secondary sex characteristics (male or female)
Anosmia
Low GnRH, LH, FSH, sex hormones
What symptoms are indicative of a hydatidiform mole?
What will be seen with labs/US?
Amenorrhea Abnormal vaginal bleeding Enlarged uterus (complete) "Snowstorm" appearance on US (complete) ^hCG
How are complete moles formed?
1 sperm + 1 empty egg –> replication –> 46XX
or
2 sperm + 1 empty egg –> 46XX/46XY
How is a partial mole formed?
2 sperm + 1 egg –> 69XXY/69XXX/69XYY
What is the difference between complete & partial mole with regard to: hCG Uterine size Risk of choriocarcinoma Fetal parts
hCG: Complete^^^ Partial^
Uterine size: Complete^ Partial = normal
Risk of choriocarcinoma: Complete = 2 Partial = rare
Fetal parts: Only in partial
What is the treatment of a hydatidiform mole?
Methotrexate + D&C
Monitor hCG for reemergence and for choriocarcinoma
What causes preeclampsia?
What is seen?
What is seen in eclampsia?
Impaired vasodilation of spiral arteries –> placental ischemia –> increased systemic maternal vascular tone
Preeclampsia = Hypertension, proteinuria, edema Eclampsia = Preeclampsia + seizures
When does preeclampsia occur?
20 weeks to 6 weeks postpartum
If earlier than 20 weeks –> mole
What are the risk factors for preeclampsia?
What is the incidence?
Occurs in 7% of pregnancies
Risk factors: Preexisting hypertension Diabetes Chronic renal disease Autoimmune disorders
What are the clinical symptoms of preeclampsia?
Headache Blurred vision Abdominal pain Edema of face & extremities Altered mental status Hyperreflexia Labs: Thrombocytopenia or hyperuricemia
What is the treatment for preeclampsia/eclampsia?
Delivery of fetus as soon as viable
Bed rest, monitoring, treatment for HTN (methyldopa)
If seizures present - IV magnesium sulfate
What is seen with placental abruption?
What can occur?
Abrupt detachment of placenta from decidua
Painful bleeding in 4rd trimester
Can cause shock, DIC, loss of fetus
What are the risk factors for placental abruption?
Smoking
Hypertension
Cocaine use
What causes placenta accreta?
What is seen?
Defective decidua –> placenta implants into myometrium
Massive bleeding seen after delivery. Often requires hysterectomy.
What are the risk factors for placenta accreta?
Prior C-section
Inflammation (PID)
Placenta previa
What is seen in HELLP syndrome?
What are the complications?
Hemolysis
Elevated Liver enzymes
Low Platelets
Risk of ARDS or cerebral hemorrhage
Often seen in conjunction with preeclampsia
What is seen with teratogen exposure in utero based on the point in gestation?
Weeks 1-2 –> spontaneous abortion
Weeks 3-8 –> organ malformation
After week 9 –> organ hypoplasia
What is seen with placenta previa?
What are the risk factors?
Placenta attaches to lower uterine segment –> painless bleeding at any point in pregnancy
Risk factors:
Multiparity
Prior C-section
Where is the most common site for an ectopic pregnancy?
What is seen?
Fallopian tubes
Presents with Hx of amenorrhea + sudden lower abdominal pain
Low hCG based on dates
Dx confirmed with US
What are the risk factors for ectopic pregnancy?
History of infertility Salpingitis (PID) Ruptured appendix Prior tubal surgery Endometriosis
Basically anything that can scar the abdominal cavity
What are the risk factors for SIDS?
SIDS = death of a healthy infant 1m-1y old
Smoking in household
Sleeping on stomach
Prematurity
How does p53 cause apoptosis?
If DNA damage is deemed irreparable –> activates Bax –> binds up Bcl-2 –> permeable mitochondrial membrane –> cytochrome C –> apoptosis
What is the mechanism of Rb as a tumor suppressor gene?
Rb binds E2F (transcription factor) & must be phosphorylated to release it –> progression in the cell cycle
When Rb is mutated, E2F is free
What are the chances of CIN reversing in the cervix?
CIN1 –> 66%
CIN2 –> 33%
CIN3 –> Rare
CIS –> never
What is a normal volume of amniotic fluid?
What can cause abnormal volumes?
0.5-1.5L
oligohydramnios (placental insuff., b/l renal agenesis, posteior urethral valves in males; can lead to Potter’s syndrome)
> 1.5L –> polyhydramnios (atresia, anencephaly)
What are the stages of the menstrual cycle?
What stages do they correspond to in the ovulatory cycle?
1) Proliferative (Follicular phase; E2)
2) Secretory (Luteal phase; Progesterone)
3) Menstruation
What causes Asherman syndrome?
What is seen?
Overaggressive D&C –> loss of basalis layer (stem cells) –> secondary amenorrhea
When are anovulatory cycles seen?
Menarche & menopause typically
Common cause of dysfunctional uterine bleeding during these times.
What causes CIN?
HPV 16, 18, 31, 33 infection
Normally cleared by the immune system. Persistent chronic infection can lead to CIN.
What virulence factors of HPV lead to CIN?
Only found in HPV 16, 18, 31, 33. These strains have both factors.
E6 –> inactivates p53
E7 –> inactivates Rb
What are the risk factors for cervical carcinoma?
Multiple sexual partners!!!
Smoking
Early age of 1st intercourse
HIV infection (AIDS-defining illness)
What is seen on an abnormal Pap smear?
Koilocytes:
Large nucleus
Irregular (“rasinoid”) nucleus
Perinuclear halo
What types of cervical carcinoma are possible?
SCC (80%)
Adenocarcinoma (15%)
Pap smear does not pick up adenocarcinoma very well. This type has not gone down in incidence.
What is seen clinically in cervical carcinoma?
What complications are seen?
Bleeding
Postcoital bleeding
Generally in middle-aged females (takes years to develop)
Complications:
Lateral invasion into bladder –> blocks ureters –> postrenal kidney failure
Rarely metastasizes
What are the causes of endometritis?
How is it treated?
Retained products of conception (no matter the outcome)
IUD
Tx: Gentamycin + Clindamycin +/- Ampicillin
What symptoms are seen with endometriosis?
Menorrhagia Dysmenorrhea Dyspareunia Infertility Pain w/ defecation or urination
What is the treatment for endometriosis?
OCP’s
NSAIDs
Leuprolide
Danazol
What is seen with adenomyosis?
What is the treatment?
Caused by endometrium within the myometrium
Menorrhagia
Dysmenorrhea
Pelvic pain
Enlarged uterus
Tx: Hysterectomy
What causes Cowden syndrome?
What is seen?
Germline PTEN mutation
GI & skin hamartomas
Macrocephaly
Breast, thyroid, endometrial carcinoma
What is extramammary Paget’s disease?
It is an intraepithelial adenocarcinoma of the vulva or penis. It does not indicate additional underlying cancer, as does Paget’s disease of the breast.
What are the risk factors for endometrial hyperplasia?
How does it present?
Presents as postmenopausal bleeding.
Anovulatory cycles
HRT
PCOS
Granulosa-Theca cell tumor
All of these ^E2 exposure
What is the best indicator of risk for endometrial hyperplasia to transform into endometrial carcinoma?
Atypia
What are the risk factors for endometrial carcinoma?
Estrogens w/out progestins Nulliparity Late menopause Obesity Diabetes HTN
What are the subtypes of endometrial carcinoma?
Endometrioid = 80% (arises from endometrial hyperplasia; PTEN)
Serous/Papillary = 20% (p53)
How does leiomyosarcoma differ from leiomyoma?
Leiomyosarcoma:
Single tumor
Irregularly shaped w/ necrosis & hemorrhage
Seen in postmenopausal women
***DOES NOT ARISE FROM LEIOMYOMA
What is the most common tumor overall in females?
Uterine fibroids (leiomyoma)
More common in blacks
What is seen clinically with uterine fibroids?
Leiomyomas: Present in 20-40y women (E2 sensitive) Usually asymptomatic Abnormal uterine bleeding Miscarriage
What is considered premature ovarian failure?
Before age 40
What is the DDx for anovulation?
Pregnancy PCOS Obesity HPO axis abnormalities Eating disorders Premature ovarian failure Hyperprolactinemia Thyroid disorders Cushing's syndrome Adrenal insufficiency
What is the pathophysiology of PCOS?
^LH –> ^Androgens –> ^Estrone (aromatized in fat) –> Feeds back to decrease FSH –> No ovulation –> Cysts & infertility
Also the high levels of androgens cause hirsutism.
What other conditions are associated with PCOS?
Insulin resistance --> development of T2DM Endometrial cancer (high estrogen)
How does PCOS present clinically?
What are the relative hormone levels?
Amenorrhea
Infertility
Obesity
Hirsutism
High LH, Testosterone, Estrogen
Low FSH
How is PCOS treated?
Weight loss Low dose OCP or medroxyprogesterone Spironolactone (for hirsutism & acne) Clomiphene (if pregnancy desired) Metformin (often enough to regain fertility)
What is the most common ovarian mass in a young woman?
Follicular cyst (unruptured Graafian follicle)
What categories of ovarian tumors are most common to what age groups?
Children & young women (0-30) –> germ cell tumors
Middle-aged (30-50) –> benign surface epithelial tumor
Older (50-80) –> malignant surface epithelial tumor
What tumor markers are associated with dysgerminoma?
Who is at risk?
Female version of seminoma
hCG and/or LDH may be elevated
Associated with Turner syndrome
What accounts for the difference in prognosis between gestational choriocarcinoma and germ cell choriocarcinoma?
Germ cell (ovarian) --> No response to chemo Gestational --> Very chemosensitive
Also germ cell choriocarcinoma shows early hematogenous spread to the lungs.
What are the relative [hCG] of pregnancy and gestational trophoblastic disease?
Choriocarcinoma > Complete mole > Partial mole > Pregnancy
What tumor marker is seen with endodermal sinus tumors?
What is seen histologically?
aka Yolk sac tumors (seen in testis & ovaries)
AFP is tumor marker
Schiller-Duval bodies present –> resemble glomeruli
What germ cell tumor is seen largely in young children?
Endodermal sinus tumors (yolk sac tumors)
Applies to both males & females
What is the most common ovarian germ cell tumor?
Teratoma (90% of germ cell tumors)
What is Struma ovarii?
Immature teratoma composed of functional thyroid tissue –> hyperthyroidism
What tumor marker is used for ovarian surface epithelial tumors?
CA-125
Good to monitor progression & recurrence, not for screening.
What type of ovarian tumor is BRCA associated with?
Most commonly serous cystadenoma/cystadenocarcinoma
BRCA1 > BRCA2 > HNPCC
Family history is the most important risk factor
What is pseudomyxoma peritonei?
A mucinous tumor (appendix > ovarian) causes accumulation of mucinous material within the peritoneum
What does a Brenner tumor look like grossly?
Histologically?
Grossly - Yellow/tan, unilateral, encapsulated
Histology - Looks like urothelial tissue, “coffee bean nuclei”
What is Meigs’ syndrome?
Triad of:
Ovarian fibroma tumor
Ascites
Hydrothorax
What is seen clinically with a Granulosa-Theca cell tumor?
Estrogen secretion by tumor:
Precocious puberty in kids
Abnormal uterine bleeding
Endometrial hyperplasia/carcinoma
What is seen histologically with Granulosa-Theca cell tumors?
Call-Exner bodies - small primitive follicles filled with eosinophilic secretions
“Call Granny”
What is seen with a Krukenberg tumor?
Mucin secreting signet-ring cell gastric adenocarcinoma metastasizes to bilateral ovaries
What are the staining patterns of extramammary Paget’s disease?
Melanoma?
Paget cells: PAS+, Keratin+, S100-
Melanoma: PAS-, Keratin-, S100+
What is vaginal adenosis?
Persistence of columnar epithelium in the upper 1/3 of the vagina. Normally the columnar epithelium (Paramesonephric) is replaced by squamous epithelium (urogenital sinus).
Can occur spontaneously or (much more commonly) due to DES exposure in-utero –> ^risk of clear cell adenocarcinoma.
What is seen in sarcoma botryoides?
Embryonal rhabdomyosarcoma presents as a grape-like mass protruding from the vagina or penis. It is seen in children <4y
What is seen on histology of sarcoma botryoides?
Cytoplasmic cross-striations
Positive staining for desmin & myoglobin (skeletal muscle origin)
What is ovarian caking?
Ovarian cancer seeds the omentum & appears cake-like.
What are the risk factors for ovarian cancer?
What is associated with lower risk?
BRCA1, BRCA2, HNPCC
OCP’s lower risk
Multiparity & breastfeeding lower risk
This is because less ovulation –> less regeneration & chance for error
What is the histology of normal breast tissue?
Inner luminal layer
Outer myoepithelial layer
This is present in both the lobules & ducts.
What are the benign breast tumors?
Fibroadenoma
Intraductal papilloma
Phyllodes tumor
What is seen with a fibroadenoma?
What is the associated risk of breast cancer?
Most common breast tumor in pre-menopausal women
Small, mobile, firm mass with sharp edges
^size & tenderness with estrogen (pregnancy, menstruation)
No increased risk of breast cancer
How does intraductal papilloma present?
What is the risk of breast cancer?
Bloody nipple discharge (usually in young woman)
Typically grows beneath areola & has 2 normal cell layers
Slight (2x) increased risk for breast cancer
What is seen histologically with Phyllodes tumor?
What is the risk for breast cancer?
Bulky mass of fibrous tissue & cysts
“Leaf-like” projections
Seen in 6th decade
Some may become malignant (vs. fibroadenoma)
With regard to breast cancer, what does nipple inversion signify?
Skin dimpling?
Nipple inversion –> has invaded central breast
Skin dimpling –> infiltration of suspensory Cooper ligaments
What is a sentinel lymph node biopsy?
Initially biopsy only the sentinel lymph nodes (the first ones that lymph will encounter). If they are positive for cancer, then excise all of the LN’s. If they are negative, you are good.
What group is at risk for triple negative breast cancer?
What is the association with prognosis?
Black women –> ER-, PR-, HER-
It is a poor prognosis.
What cancers are seen with BRCA1 & BRCA2 mutation?
BRCA1 - Breast (medullary^), Ovarian (serous)
BRCA2 - breast carcinoma in males
What are the risk factors for male breast cancer?
BRCA2
Klinefelter’s syndrome
What are the subtypes of mastitis?
What are their causes?
Acute mastitis:
Breastfeeding –> S. aureus infection
Periductal mastitis:
Smoking –> relative Vit. A deficiency –> squamous metaplasia in lactiferous ducts –> keratin plugging –> inflammation
How do the subtypes of mastitis present?
Acute mastitis - redness & inflammation in a breastfeeding mom
Periductal - subareolar mass with nipple retraction
Green-brown nipple discharge
Mammary duct ectasia
Secondary to inflammation & dilation of subareolar duct. Arises in multiparous postmenopausal woman (must DDx from breast cancer).
What is comedocarcinoma?
What is seen on histology?
Comedocarcinoma is a subtype of DCIS
Caseous necrosis seen in the center of the duct with dystrophic calcification of the necrotic tissue. Surrounded by cancer cells.
What is the most common type of breast cancer?
Invasive ductal carcinoma
Also the worst prognosis
What is seen on histology of invasive lobular carcinoma?
Orderly single file cells
This is because E-cadherin is mutated early so the cells can lose their architecture. Often multifocal & seen bilaterally.
What is seen on histology with medullary breast carcinoma?
What is the prognosis?
Subtype of ductal carcinoma
Lymphocytic infiltrate
Has a good prognosis
What is seen with inflammatory breast carcinoma?
What is the prognosis?
Peau d’orange
Invasion of dermal lymphatics by the breast carcinoma
Subtype of ductal carcinoma with a poor prognosis
What causes mammary Paget’s disease?
Paget cells within the epidermis (large cells w/ nuclear halo)
Indicates DCIS that has extended along the duct to the nipple.
What is seen on staining for HER-2?
ER/PR?
Her-2 –> cell surface stains positive (EGFR tyrosine kinase rec.)
ER/PR –> nucleus stains positive (translocate to nucleus upon binding the hormones)
How does fibrocystic disease present?
Lumpy breasts in a young woman
Premenstrual breast pain & fluctuation of size
Often bilateral
What are the histologic types of fibrocystic change & their relative chances of developing cancer?
Nonproliferative (blue dome cysts, apocrine metaplasia, fibrosis) –> no ^ risk
Hyperplasia w/ no atypia --> 2x ^ risk Sclerosing adenosis (calcifications & ^ # of acini) --> 2x ^ risk
Prolferative w/ atypia –> 5x risk
CIS –> 10x risk
How does fat necrosis of the breast occur?
Painless lump following trauma (usually can’t recall)
Calcified (saponification) on mammography
What can cause gynecomastia?
Hyperestrogenism (cirrhosis, tumor, puberty, old age)
Klinefelter’s syndrome
Illicit drugs
Spironolactone, Digitalis, Cimetidine, Alcohol, Ketoconazole
(Some Drugs Create Awkward Knockers)
What other embryologic abnormality is epispadias associated with?
Bladder exstrophy
Bladder wall exposed out of the abdominal wall.
What causes lymphogranuloma venereum?
Chlamydia trachomatis L1-L3
What are the precursor lesions to penile SCC?
Bowen disease - leukoplakia on the shaft
Erythroplasia of Queyrat - erythroplakia on glans
Bowenoid papulosis - reddish papules (doesn’t invade)
What organs can be inflamed due to mumps?
Parotitis
Orchitis
Meningitis
Your balls get as big as POM POMs
What lobes are affected by BPH?
Prostate cancer?
BPH - periurethral (middle & lateral) lobe
Cancer - peripheral (posterior) lobe
What are the pharmacologic treatments for BPH?
Alpha1 antagonists (Terazosin, tamsulosin)
5-alpha-reductase inhibitors (Finasteride)
What PSA level is typically seen in BPH?
Prostatic adenocarcinoma?
BPH = 4-10 Cancer = > 10
What tumor markers are used for prostate cancer?
PSA Prostatic acid phosphatase (PAP) Alkaline phosphatase (if mets to bone)
What sequelae can result from cryptorchidism?
Infertility
Germ cell tumors (seminoma)
Low testosterone (if bilateral)
How does a seminoma present grossly?
Histologically?
Gross: Homogenous, no necrosis, no hemorrhage
Histo: Fried egg appearance
What tumor markers are elevated in seminomas?
hCG (sometimes)
Placental alkaline phosphatase (PLAP)
What is the prognosis of a seminoma?
Radiosensitive
Late mets
Excellent prognosis
What germ cell tumor may produce paraneoplastic syndromes?
Immature teratoma (females): Struma ovarii --> Hyperthyroidism
Choriocarcinoma (hCG):
Hyperthyroidism
Gynecomastia in males
hCG at high concentrations binds TSH & LH receptors
What is the prognosis of teratomas?
In females –> usually mature & benign
In males –> even mature ones are malignant
What serum markers are elevated in teratomas?
Male - possibly AFP or hCG
Why are testicular tumors not biopsied?
~90% are germ cell tumors –> malignant
Also, biopsy could seed the scrotum
What are the testicular germ cell tumors?
Seminoma Endodermal sinus (yolk sac) Choriocarcinoma Teratoma Embryonal carcinoma
What is grossly with a Leydig cell tumor?
Histologically?
Grossly - Golden brown color
Histo - Reinke crystals
What is the most common testicular cancer in older men?
Metastatic DLBC lymphoma
Usually bilateral
What causes a hydrocele?
Incomplete closure of the processus vaginalis
What are the antiandrogens?
Finasteride (5-alpha-reductase inhibitor)
Flutamide (androgen antagonist)
Ketoconazole (inhibits 17-alpha-hydroxylase)
Spironolactone (inhibits steroid binding)
What are the SERMs?
Clomiphene
Tamoxifen
Raloxifene
What is the mechanism of Clomiphene?
Toxicities?
Partial agonist at ER in hypothalamus (SERM) –> prevents normal feedback inhibition –> ^GnRH release
Toxicities:
Hot flashes
Multiparity
Visual disturbances
What is Raloxifene used for?
Treats osteoporosis
Agonist on bone
Antagonist on uterus & breast
What are the aromatase inhibitors?
What are they used for?
Anastrozole (reversible)
Exemestane (irreversible)
Used in ER+ breast cancer in postmenopausal women.
What is the mechanism of Mifepristone?
What is it used for?
What are the side effects?
Mifepristone is a progesterone antagonist –> abortion
It is administered with Misoprostol (PGE1)
Side effects:
Heavy bleeding
N/V
Abdominal pain
What are the contraindications of OCP’s?
Smokers > 35y
Hx of thromboembolism
Hx of estrogen-dependent tumor
What is Tamsulosin?
What is its use?
Selective Alpha-1a/d agonist used to treat symptoms of BPH by relaxing smooth muscle contraction
Alpha1b = vascular receptors
What toxicities are seen with Sildenafil/Vardenafil?
Headache
Flushing
Blue/green vision changes
Life-threatening hypotension if taken with nitrates
What is Danazol?
What are its uses?
Synthetic androgen partial agonist
Used for endometriosis & hereditary angioedema