Embryo/Repro Flashcards
1
Q
What is seen with a mutation in the Sonic Hedgehog gene?
A
Holoprosencephaly
2
Q
What is the function of the Wnt-7 gene?
A
Ventral-dorsal axis organization
3
Q
What is the function of the FGF gene?
A
Found at apical ectodermal ridge (tip of limb). Stimulates mitosis of underlying mesoderm –> lengthening of limbs
4
Q
What is the seen with mutation of the Homeobox genes?
A
Hox genes orient the embryo in the cranial-caudal direction. Mutations cause limbs in the wrong places.
5
Q
When is a fetus most susceptible to teratogens?
A
Weeks 3-8
This is the embryonic period & is when most organs are formed.
6
Q
When does gastrulation occur?
A
3 layers = Week 3 (trilaminar)
7
Q
When during embryogenesis are the limbs formed?
A
4 limbs = Week 4
8
Q
When can the sex of a baby be determined by US?
A
Week 10
9
Q
When does the neural tube form during embryogenesis?
A
Weeks 3-4
10
Q
What structures are formed from the neural crest?
A
PNS neurons Schwann cells Melanocytes Parafollicular thyroid cells Pia & arachnoid Bones of the skull Aorticopulmonary septum
11
Q
What are the mesodermal defects?
A
CV LATER:
Cardiac defects Vertebral defects Limb defects Anal atresia Tracheo-Esophageal fistula Renal defects
12
Q
What structures are formed from the endoderm?
A
Lungs Gut tube epithelium Liver Gallbladder Pancreas Thymus Thyroid follicular cells Parathyroid
13
Q
What is the difference between agenesis & aplasia?
A
Agenesis = absent primordial tissue
Aplasia = Primordial tissue was present but organ is absent
14
Q
What is the difference between Deformation & Malformation?
A
Malformation = intrinsic & occurred during embryogenesis
Deformation = Extrinsic & occurred after embryogenesis
15
Q
What is the embryologic effect of ACE inhibitors?
A
Renal damage
16
Q
What is the embryologic effect of alkylating agents?
A
Absence of digits & other anomalies
17
Q
What is the embryologic effect of aminoglycosides?
A
CNVIII toxicity
Just like how they are ototoxic in adults
18
Q
What is the embryologic effect of Lithium?
A
Ebstein’s anomaly
Ebstein’s = Atrialized RV = most of the right heart is atrium
19
Q
What is the embryologic effect of phenytoin?
A
Fetal hydantoin syndrome:
Microcephaly Dysmorphic craniofacial features Hypoplastic distal phalanges & nails Mental retardation Cardiac defects Intrauterine growth restriction
20
Q
What is the embryologic effect of Tetracyclines?
A
Discolored teeth
21
Q
What is the embryologic effect of thalidomide?
A
“Flipper” limb defects
ThaLIMBdomide
22
Q
What is the embryologic effect of Valproic acid?
A
Inhibits maternal folate absorption –> neural tube defects
23
Q
What is the embryologic effect of warfarin?
A
Bone deformities
Fetal hemorrhage
Ocular abnormalities
Use heparin during pregnancy
24
Q
What is seen with cocaine use during pregnancy?
A
Abruptio placentae
Abnormal fetal development
Fetal addiction
25
What is seen with smoking during pregnancy?
Premature delivery
IUGR
ADHD
26
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
27
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
28
What are the chorionic villi composed of?
| Which cell type secretes hCG?
Cytotrophoblasts (inner layer)
| Sincytiotrophoblasts (outer layer) - secrete hCG
29
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
30
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
31
What is derived from the 1st aortic arch?
Maxillary artery
MS CARD
32
What is derived from the 2nd aortic arch?
Stapedial artery & hyoid artery
MS CARD
33
What is derived from the 3rd aortic arch?
Common Carotid & part of internal Carotid
MS CARD
34
What is derived from the 4th aortic arch?
Aortic arch & proximal R. subclavian
MS CARD
35
What is derived from the 5th aortic arch
Nothing (regresses)
MS CARD
36
What is derived from the 6th aortic arch?
Ductus arteriosus & proximal pulmonary artery
MS CARD
37
What types of tissue is the branchial (pharyngial) apparatus composed of?
Clefts - Ectoderm
Arches - Mesoderm
Pouches - Endoderm
38
What do the branchial clefts develop into?
1st cleft --> EAM
All others are obliterated. If one is not --> branchial cleft cyst within lateral neck
39
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)
40
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
41
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)
42
What is derived from the 3rd pharyngeal (branchial) arch?
GlossoPHARYNGEAL nerve (CNIX)
Greater horn of hyoid
styloPHARYNGEOUS
43
What causes a congenital pharyngocutaneous fistula?
Persistent 3rd branchial cleft & pouch --> fistula to lateral neck
44
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
```
45
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
46
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
47
What is derived from the 2nd branchial (pharyngeal) pouch?
Palatine tonsil epithelium
Ear, Tonsils, bottom-To-top
48
What is derived from the 3rd branchial (pharyngeal) pouch?
dorsal --> inferior parathyroids (bottom)
ventral --> thymus (to)
Ear, Tonsils, bottom-To-top
49
What is derived form the 4th branchial (pharyngeal) pouch?
Superior parathyroids (top)
Ear, Tonsils, bottom-To-top
50
What causes a cleft lip?
Maxillary & medial nasal processes do not fuse
51
What gene causes male development?
SRY gene --> Testis determining factor
52
What is derived from the mesonephric duct?
aka Wolffian duct --> SEED
Seminal vesicles
Epididymis
Ejaculatory duct
Ductus deferens
53
What is seen with congenital 5-alpha reductase deficiency?
Male internal genitalia
Ambiguous external genitalia until puberty
(DHT necessary)
54
What causes hypospadias?
Failure of urethral folds to close
55
What causes epispadias?
Faulty positioning of the genital tubercle
56
What is the lymphatic drainage of the vagina?
Proximal 2/3 --> obturator, external iliac, hypogastric nodes
Distal 1/3 --> superficial inguinal nodes
57
What ligament contains the ovarian vessels?
| What does the ligament connect?
Suspensory ligament
Anchors ovaries to the lateral pelvic wall
58
What ligament contains the uterine vessels?
| What does the ligament connect?
Cardinal ligament
Anchors the cervix to side wall of the pelvis
59
What ligament contains the Artery of Sampson?
| What does the ligament connect?
Round ligament
Uterine fundus --> Labia majora
60
What ligament in the female pelvis travels through the inguinal canal?
Round ligament
| Uterine fundus --> labia majora
61
What are the components of the broad ligament?
Mesometrium (lower portion)
Mesosalpinx (upper portion)
Mesovarium (lies on ovary)
62
What is connected by the ligament of the ovary?
Connects the ovary to the uterus
63
What is the pathway of sperm to exit the male?
```
SEVEN UP:
Seminiferoustubules
Epididymis
Vas deferens
Ejactulatory duct
(Nothing)
Urethra
Penis
```
64
What nerves are responsible for the male sexual response?
Erection - pelvic nerve (parasympathetic)
Emission - hypogastric nerve (sympathetic)
Ejaculation - pudendal nerve
65
What is secreted by Sertoli cells?
Embryogenesis - Mullerian inhibitory factor
Adult:
Inhibin - feedback inhibition to FSH
Androgen binding protein - keep local [T] high
66
What forms the blood-testis barrier?
Tight junctions between Sertoli cells
67
How does increased temperature affect the testis?
Decreased sperm production
Decreased inhibin production
Normal testosterone production
68
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
69
What is spermatogenesis?
| Spermiogenesis?
Spermatogenesis is the whole process
| Spermiogenesis is spermatid --> mature spermatozoon
70
Where is aromatase found in adult males?
Leydig cells
| Adipocytes
71
What is the relative potency of endogenous estrogens?
| Where are they produced?
Estradiol > Estrone > Estriol
```
E2 = ovary
E1 = adipose
E3 = placenta
```
72
What is the effect of estrogen on lipoprotein levels?
^HDL
| Decreased LDL
73
Describe Estrogen production in the ovary
LH stimulates theca cells --> Cholesterol --> Androstenedione via Desmolase
FSH stimulates granulosa cells --> Androstenedione --> Estrogen via Aromatase
74
How much estrogen is in a pregnant woman?
50x normal E2 & E1
| 1000x normal E3
75
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
```
76
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
77
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
78
What is a normal menstrual cycle length?
21-35 days
35 = oligomenorrhea
79
What is menorrhagia?
| Metrorrhagia?
Menorrhagia - heavy or prolonged bleeding
Metrorrhagia - irregular menstruation
80
Why is body temperature a marker for ovulation?
Ovulation --> corpus luteum releases progesterone --> ^temp
81
What is Mittelschmerz?
Rupture of a follicle --> small bleed into peritoneum --> irritation that can mimic appendicitis
82
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)
83
What are the stages of ovum development & their ploidy?
Oogonium (2n, 2c)
Primary oocyte (2n, 4c)
Secondary oocyte (1n, 2c)
Ovum (1n, 1c)
84
What is hCG detectable?
```
In blood at 1 week
In urine (home test) at 2 weeks
```
85
When does hCG peak during pregnancy?
| What secretes it?
Week 10
It is secreted by syncytiotrophoblasts
86
When does implantation of an embryo occur?
6 days after fertilization
87
What is the function of prolactin?
| Oxytocin?
Prolactin - Induces/maintains lactation & inhibits GnRH
Oxytocin - Milk letdown & causes uterine contractions
88
Where is progresterone synthesized from during pregnancy?
1st trimester = corpus luteum (maintained by hCG)
| 2nd & 3rd trimesters = placenta
89
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.
90
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
91
What is the genetic cause of Turner syndrome (precisely)?
```
60% = complete monosomy
30% = mosaicism
10% = structural abnormality of X chromosome
```
92
What is seen in double Y males?
XYY genotype
Tall
Severe acne
Antisocial behavior
Autism spectrum disorders
93
What causes female pseudohermaphroditism?
Ovaries present (XX) but external genitalia are virilized or ambiguous
Caused by inappropriate exposure to androgens during early gestation
94
What causes male pseudohermaphroditism?
Testes present (XY) but external genitalia are female or ambiguous
Most common cause if androgen insensitivity syndrome
95
What is seen with true hermaphroditism?
46XX or 47XXY
Both ovary and testicular tissue present. Ambiguous genitalia. This is very rare.
96
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
```
97
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)
98
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
99
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
```
100
How are complete moles formed?
1 sperm + 1 empty egg --> replication --> 46XX
or
2 sperm + 1 empty egg --> 46XX/46XY
101
How is a partial mole formed?
2 sperm + 1 egg --> 69XXY/69XXX/69XYY
102
```
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
103
What is the treatment of a hydatidiform mole?
Methotrexate + D&C
Monitor hCG for reemergence and for choriocarcinoma
104
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
```
105
When does preeclampsia occur?
20 weeks to 6 weeks postpartum
If earlier than 20 weeks --> mole
106
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
```
107
What are the clinical symptoms of preeclampsia?
```
Headache
Blurred vision
Abdominal pain
Edema of face & extremities
Altered mental status
Hyperreflexia
Labs: Thrombocytopenia or hyperuricemia
```
108
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
109
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
110
What are the risk factors for placental abruption?
Smoking
Hypertension
Cocaine use
111
What causes placenta accreta?
| What is seen?
Defective decidua --> placenta implants into myometrium
Massive bleeding seen after delivery. Often requires hysterectomy.
112
What are the risk factors for placenta accreta?
Prior C-section
Inflammation (PID)
Placenta previa
113
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
114
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
115
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
116
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
117
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
118
What are the risk factors for SIDS?
SIDS = death of a healthy infant 1m-1y old
Smoking in household
Sleeping on stomach
Prematurity
119
How does p53 cause apoptosis?
If DNA damage is deemed irreparable --> activates Bax --> binds up Bcl-2 --> permeable mitochondrial membrane --> cytochrome C --> apoptosis
120
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
121
What are the chances of CIN reversing in the cervix?
CIN1 --> 66%
CIN2 --> 33%
CIN3 --> Rare
CIS --> never
122
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)
123
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
124
What causes Asherman syndrome?
| What is seen?
Overaggressive D&C --> loss of basalis layer (stem cells) --> secondary amenorrhea
125
When are anovulatory cycles seen?
Menarche & menopause typically
Common cause of dysfunctional uterine bleeding during these times.
126
What causes CIN?
HPV 16, 18, 31, 33 infection
Normally cleared by the immune system. Persistent chronic infection can lead to CIN.
127
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
128
What are the risk factors for cervical carcinoma?
Multiple sexual partners!!!
Smoking
Early age of 1st intercourse
HIV infection (AIDS-defining illness)
129
What is seen on an abnormal Pap smear?
Koilocytes:
Large nucleus
Irregular ("rasinoid") nucleus
Perinuclear halo
130
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.
131
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
132
What are the causes of endometritis?
| How is it treated?
Retained products of conception (no matter the outcome)
IUD
Tx: Gentamycin + Clindamycin +/- Ampicillin
133
What symptoms are seen with endometriosis?
```
Menorrhagia
Dysmenorrhea
Dyspareunia
Infertility
Pain w/ defecation or urination
```
134
What is the treatment for endometriosis?
OCP's
NSAIDs
Leuprolide
Danazol
135
What is seen with adenomyosis?
| What is the treatment?
Caused by endometrium within the myometrium
Menorrhagia
Dysmenorrhea
Pelvic pain
Enlarged uterus
Tx: Hysterectomy
136
What causes Cowden syndrome?
| What is seen?
Germline PTEN mutation
GI & skin hamartomas
Macrocephaly
Breast, thyroid, endometrial carcinoma
137
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.
138
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
139
What is the best indicator of risk for endometrial hyperplasia to transform into endometrial carcinoma?
Atypia
140
What are the risk factors for endometrial carcinoma?
```
Estrogens w/out progestins
Nulliparity
Late menopause
Obesity
Diabetes
HTN
```
141
What are the subtypes of endometrial carcinoma?
Endometrioid = 80% (arises from endometrial hyperplasia; PTEN)
Serous/Papillary = 20% (p53)
142
How does leiomyosarcoma differ from leiomyoma?
Leiomyosarcoma:
Single tumor
Irregularly shaped w/ necrosis & hemorrhage
Seen in postmenopausal women
***DOES NOT ARISE FROM LEIOMYOMA
143
What is the most common tumor overall in females?
Uterine fibroids (leiomyoma)
More common in blacks
144
What is seen clinically with uterine fibroids?
```
Leiomyomas:
Present in 20-40y women (E2 sensitive)
Usually asymptomatic
Abnormal uterine bleeding
Miscarriage
```
145
What is considered premature ovarian failure?
Before age 40
146
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
```
147
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.
148
What other conditions are associated with PCOS?
```
Insulin resistance --> development of T2DM
Endometrial cancer (high estrogen)
```
149
How does PCOS present clinically?
| What are the relative hormone levels?
Amenorrhea
Infertility
Obesity
Hirsutism
High LH, Testosterone, Estrogen
Low FSH
150
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)
```
151
What is the most common ovarian mass in a young woman?
Follicular cyst (unruptured Graafian follicle)
152
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
153
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
154
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.
155
What are the relative [hCG] of pregnancy and gestational trophoblastic disease?
Choriocarcinoma > Complete mole > Partial mole > Pregnancy
156
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
157
What germ cell tumor is seen largely in young children?
Endodermal sinus tumors (yolk sac tumors)
Applies to both males & females
158
What is the most common ovarian germ cell tumor?
Teratoma (90% of germ cell tumors)
159
What is Struma ovarii?
Immature teratoma composed of functional thyroid tissue --> hyperthyroidism
160
What tumor marker is used for ovarian surface epithelial tumors?
CA-125
Good to monitor progression & recurrence, not for screening.
161
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
162
What is pseudomyxoma peritonei?
A mucinous tumor (appendix > ovarian) causes accumulation of mucinous material within the peritoneum
163
What does a Brenner tumor look like grossly?
| Histologically?
Grossly - Yellow/tan, unilateral, encapsulated
Histology - Looks like urothelial tissue, "coffee bean nuclei"
164
What is Meigs' syndrome?
Triad of:
Ovarian fibroma tumor
Ascites
Hydrothorax
165
What is seen clinically with a Granulosa-Theca cell tumor?
Estrogen secretion by tumor:
Precocious puberty in kids
Abnormal uterine bleeding
Endometrial hyperplasia/carcinoma
166
What is seen histologically with Granulosa-Theca cell tumors?
Call-Exner bodies - small primitive follicles filled with eosinophilic secretions
"Call Granny"
167
What is seen with a Krukenberg tumor?
Mucin secreting signet-ring cell gastric adenocarcinoma metastasizes to bilateral ovaries
168
What are the staining patterns of extramammary Paget's disease?
Melanoma?
Paget cells: PAS+, Keratin+, S100-
| Melanoma: PAS-, Keratin-, S100+
169
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.
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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
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What is seen on histology of sarcoma botryoides?
Cytoplasmic cross-striations
| Positive staining for desmin & myoglobin (skeletal muscle origin)
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What is ovarian caking?
Ovarian cancer seeds the omentum & appears cake-like.
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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
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What is the histology of normal breast tissue?
Inner luminal layer
Outer myoepithelial layer
This is present in both the lobules & ducts.
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What are the benign breast tumors?
Fibroadenoma
Intraductal papilloma
Phyllodes tumor
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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
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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
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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)
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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
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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.
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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.
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What cancers are seen with BRCA1 & BRCA2 mutation?
BRCA1 - Breast (medullary^), Ovarian (serous)
BRCA2 - breast carcinoma in males
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What are the risk factors for male breast cancer?
BRCA2
| Klinefelter's syndrome
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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
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How do the subtypes of mastitis present?
Acute mastitis - redness & inflammation in a breastfeeding mom
Periductal - subareolar mass with nipple retraction
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Green-brown nipple discharge
Mammary duct ectasia
Secondary to inflammation & dilation of subareolar duct. Arises in multiparous postmenopausal woman (must DDx from breast cancer).
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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.
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What is the most common type of breast cancer?
Invasive ductal carcinoma
Also the worst prognosis
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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.
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What is seen on histology with medullary breast carcinoma?
| What is the prognosis?
Subtype of ductal carcinoma
Lymphocytic infiltrate
Has a good prognosis
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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
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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.
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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)
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How does fibrocystic disease present?
Lumpy breasts in a young woman
Premenstrual breast pain & fluctuation of size
Often bilateral
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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
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How does fat necrosis of the breast occur?
Painless lump following trauma (usually can't recall)
| Calcified (saponification) on mammography
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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)
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What other embryologic abnormality is epispadias associated with?
Bladder exstrophy
Bladder wall exposed out of the abdominal wall.
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What causes lymphogranuloma venereum?
Chlamydia trachomatis L1-L3
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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)
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What organs can be inflamed due to mumps?
Parotitis
Orchitis
Meningitis
Your balls get as big as POM POMs
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What lobes are affected by BPH?
| Prostate cancer?
BPH - periurethral (middle & lateral) lobe
Cancer - peripheral (posterior) lobe
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What are the pharmacologic treatments for BPH?
Alpha1 antagonists (Terazosin, tamsulosin)
5-alpha-reductase inhibitors (Finasteride)
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What PSA level is typically seen in BPH?
| Prostatic adenocarcinoma?
```
BPH = 4-10
Cancer = > 10
```
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What tumor markers are used for prostate cancer?
```
PSA
Prostatic acid phosphatase (PAP)
Alkaline phosphatase (if mets to bone)
```
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What sequelae can result from cryptorchidism?
Infertility
Germ cell tumors (seminoma)
Low testosterone (if bilateral)
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How does a seminoma present grossly?
| Histologically?
Gross: Homogenous, no necrosis, no hemorrhage
Histo: Fried egg appearance
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What tumor markers are elevated in seminomas?
hCG (sometimes)
| Placental alkaline phosphatase (PLAP)
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What is the prognosis of a seminoma?
Radiosensitive
Late mets
Excellent prognosis
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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
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What is the prognosis of teratomas?
In females --> usually mature & benign
| In males --> even mature ones are malignant
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What serum markers are elevated in teratomas?
Male - possibly AFP or hCG
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Why are testicular tumors not biopsied?
~90% are germ cell tumors --> malignant
Also, biopsy could seed the scrotum
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What are the testicular germ cell tumors?
```
Seminoma
Endodermal sinus (yolk sac)
Choriocarcinoma
Teratoma
Embryonal carcinoma
```
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What is grossly with a Leydig cell tumor?
| Histologically?
Grossly - Golden brown color
Histo - Reinke crystals
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What is the most common testicular cancer in older men?
Metastatic DLBC lymphoma
Usually bilateral
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What causes a hydrocele?
Incomplete closure of the processus vaginalis
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What are the antiandrogens?
Finasteride (5-alpha-reductase inhibitor)
Flutamide (androgen antagonist)
Ketoconazole (inhibits 17-alpha-hydroxylase)
Spironolactone (inhibits steroid binding)
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What are the SERMs?
Clomiphene
Tamoxifen
Raloxifene
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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
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What is Raloxifene used for?
Treats osteoporosis
Agonist on bone
Antagonist on uterus & breast
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What are the aromatase inhibitors?
| What are they used for?
Anastrozole (reversible)
Exemestane (irreversible)
Used in ER+ breast cancer in postmenopausal women.
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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
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What are the contraindications of OCP's?
Smokers > 35y
Hx of thromboembolism
Hx of estrogen-dependent tumor
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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
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What toxicities are seen with Sildenafil/Vardenafil?
Headache
Flushing
Blue/green vision changes
Life-threatening hypotension if taken with nitrates
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What is Danazol?
| What are its uses?
Synthetic androgen partial agonist
Used for endometriosis & hereditary angioedema
