Life Cycles Pathology

Front 1

Dysfunctional uterine bleeding (definition, systemic causes)

Back 1

abnormal bleeding during or between menstrual periods that is caused by abnormalities in the menstrual cycle or systemic diseases, not caused by organic abnormalities.
-- Systemic causes include general bleeding disorders
such as ITP, liver cirrhosis, leukemia, and
hypothyroidism, etc.
--- After excluding these causes, majority are related to anovulation, (factors affecting the
hypothalamic pituitary axis)

Front 2

Physiologic anovulation causes vs. Pathologic causes

Back 2

Anovulation sometimes is
physiologic, such as adolescence, perimenopause, pregnancy, and lactation.
Pathologic causes of anovulation mostly include polycystic ovarian syndrome, hypothalamic dysfunction, hypothyroidism, hyperprolactinemia, pituitary disorders, premature ovarian failure, and iatrogeneic reasons like medication.

Front 3

Abnormal uterine bleeding

Back 3

Abnormal uterine bleeding (AUB) - the occurrence
of bleeding at times other than expected menses.
majority of cases just after menarche or in the perimenopausal period. It can be caused by a wide variety of local and
systemic disease or related to drugs.
- pregnancy
- structural uterine pathology (eg, fibroids, polyps, adenomyosis),
- anovulation,
- a disorder of hemostasis
- neoplasia.
Trauma and infection are less common.
b. Organic abnormalities - chronic endometritis,
leiomyoma, endometrial polyp, endometrial
neoplasms.

Front 4

Leiomyoma

Back 4

not restricted to uterus, but in uterus behaves as estrogen target tissue
 Incidence: The most common tumor in women; occur in 25% women
during reproductive years; multiple lesions common.
 Cause: Localized, heightened sensitivity to normal levels of estrogen.
 Effect: Asymptomatic, mass, abnormal bleeding (if submucosal), impaired
fertility, dystocia (difficult labor), and rarely sarcoma.
 Morphology: Characteristic gross appearance (whorled, gray-white,
sharp circumscription). Location intramural > subserous > submucous.
Microscopic: mature smooth muscle with rare mitoses.
 Treatment: None unless symptomatic; myomectomy, hysterectomy.
 Clinical course: Develop and grow in reproductive years; degenerate and shrink after menopause if estrogen level is low.

Front 5

Endometriosis (definition, sites of involvement, epi, clinical presentation, gross path)

Back 5

presence of endometerial glands or stroma outside the uterine cavity. This tissie remains (partially) hormonally responsive and undergoes cyclic menstual changes with periodic bleeding.
Sites - ovaries, uterine ligaments, rectovaginal septum, pelvic peritoneum, lapartomy scars, and rarely the umbilicus, vulva, vagina, or appendix.
Epi - disease of repro years (30-40's). 10% of women
clinical manifestations: severe dysmenorrhea, menstrual irregularities, recurrent pelvic pain, 30-40% infertility. pain on defectation or dysuria if rectum/bladder involved.
Gross - foci appear red-blue to yellow-brown subserosal nodules. In extensive disease, organizing foci of hemorrhage can cause extensive fibrous adhesions between ovaries, tubes, and other intrapelvic structures. Ovaries may become markedly distorted by large hemorrhagic cysts (chocolate cysts).
Micro - endometrial stroma or endometrial glands, and hemosiderin pigment.

Front 6

Pathophys theories of endometriosis

Back 6

1) The regurgitation theory that involves retrograde menstruation through the fallopian tubes.
2) The metaplastic theory that involves de novo formation of endometrium from the coelomic epithelium. Ovarian endometriosis is mostly derived from a metaplastic process. A good example is
the demonstration of “Initial Endometriosis”.
3) The vascular or lymphatic dissemination theory that involves dissemination through the pelvic veins and lymphatics and explains the presence of lesion in distant location such as lungs.

Front 7

Adenomyosis

Back 7

endometrial tissue deep within the myometrial wall (at least 2-3 mm beneath basalis) with connection to the surface endometrium (may represent downgrowth of endometrium into the myometrium). Cause unkown, 20% of uteri.
Hemorrhage within these small nests menorrhagia, colicky dysmenorrhea, dyspareunia, and premenstrual pelvic pain.
Gross - variable thickening of myometrium and numerous hemorrhagic cysts. Microscopically, there is invagination of the basalis with irregular nests of endometrial stroma with/without glands.

Front 8

Warfarin (teratogen)

Back 8

POM - growth deficiency, severe nasal hypoplasia, calcific stippling of the epiphyses of the long bones.
Critical pd is 6-9 wks. crosses placenta
Give heparin instead (does not cross placenta)

Front 9

Isotretinoin (teratogen)

Back 9

POM - microtia, anotia (small/absent ear), CNS defects, thumic abnormalities, cardiac defects. Seein in 30% of pregnancies exposed in 1st trimester. inc risk of neurodev problems. iPLEDGE program

Front 10

Lithium (teratogen)

Back 10

POM - heart defects, esp. Ebstein's anomaly (tricuspid valve prob).
Risk is 1-5%. Monitor serum levels throughout pregnancy

Front 11

ACE inhibitors/ARBS (teratogens)

Back 11

POM - assoc with heart defects. Renal tubular dysplasia --> oligohydramnios, Potter's signs, pulmonary hypoplasia.
blocks fetal ACE activity affecting system/renal hemodynamics.

2nd and 3rd trimester use

Front 12

Valproic acid (teratogen)

Back 12

POM - facial abnormalities like low hairline, wide set eyes. Heart defects, neural tube defects (1-2%). Highest risk of neurodevelopment problems are seen with valproate-exposed babies (in comp to other anticonvulsants)

Front 13

Tetrycycline (teratogen)

Back 13

POM - teeth discoloration
Critical pd is after 4 mos

Front 14

Mercury (teratogen)

Back 14

congenital minamata disease: mental retardation, dysarthria, chorea, ataxia, hypersalivation, abnormal reflexes, growth retardation. (pregnant women shouldt ear fish > 12 oz)

Front 15

Diabetes (maternal metabolic state ~ teratogen)

Back 15

inc risk to fetus up to ~8%. POM - abnormalities of spine and lower extremities, heart, kidney.

Front 16

Maternal PKU (as teratogen)

Back 16

High levels are toxic to developing brain and heart. mom should go on stringent PKU diet prior to attempting a pregnancy.

Front 17

Ionizing radiation

Back 17

Timing:
 Interestingly, even VERY high dose exposures is during Preimplantation = NOT
associated with malformations!
 Although 70% embryonic LOSS rate is estimated!
 Organogenesis:
 Most susceptible period
 Doses of 5 rads or less = NO malformation or growth retardation
 Growth and differentiation
 Doses of 10 rads or less = NO malformation or growth retardation!
 Microcephaly
 Mental retardation
 Seizures
 Growth retardation
 Minor anomalies of the yes
 Increased risk of carcinogenesis
Radiation exposure exampls:
 Chest XR = 0.1 rad
 Spiral CT = 5 rad

Front 18

Cocaine

Back 18

And related methamphetamine agents = two most common illicit drugs used during pregnancy
o Associated problems:
 Miscarriage
 Premature delivery
 Placental abruption
o PofM:
 Sympatheomimetic properties = contracted blood vessels and increased heart rate
 Results in hypoxic fetal blood flow = vascular disruption and cerebral infarctions!

Front 19

Fetal hydantoin syndrome (Dilantin)

Back 19

POM: growth deficiency, neurodev delay, microcephaly, wide set eyes, low anterior hairline, short fingers, with nail hypoplasia. risk is 10-15% in exposed children.

Metabolized through arene oxide pathway (epoxide hydrolase).
Tegretol kids have similar phenotypes.

Front 20

Acute mastitis

Back 20

Limited to lactating breast.
Symptoms - painfel, erythematous breast, usually w/ fever
Treat - antibiotics for S. aureus, or streptococci.
Note - inflammatory breast cancer looks a lot like acute mastitis, so if this presents in a nonlactating woman suspect cancer!

Front 21

Periductal mastitis (recurrent subarerolar abscess)

Back 21

Epi - women AND men. 90% are smokers!
Px - painful erythematous subareolar mass that often recurs.
Patho - duct rupture with intense chronic and granulomatous inflammation in response to spilled entrapped keratin that accumulates from keratinizing squamous epithelium, extending t an abnormal depth in the nipple ducts.
Treat - surgical. Antibiotics is superimposed infection

Front 22

Mammary duct ectasia

Back 22

Epi - 5th/6th decade. Not assoc with cgarette smoking
Px - poorly defined palpable periareolar mass, often with thick white nipple secretions. Can be mistaken for cacinoma.

Front 23

Fat necrosis

Back 23

Epi - hx of trauma
Px - painless palpable mass or mammographic abnormality that can be confused with breast cancer.

Front 24

Fibroadenoma

Back 24

Epi - most common benign tumor of female braest. Frequently <30 years, but any premenopausal age.
Px - Palpable mass in young or mammographic abnormality if older. Can be bilateral & multiple. Waxes and wanes during menstrual cycle since hormonally sensitive.
Histo - delicate, often myxoid stroma enclosing glandular and cystic spaces lined by bilayered epithelium. Stroma becomes hylanized with aging.
Note - no well-defined risk of breast cancer

Front 25

Phyllodes Tumor

Back 25

Epi - most present in 6th decade. Uncommon tumor (also intraloular)
Px - usually palpable mass. Few cm to huge, bulbous protrusions and slit-like spaces.
Histo - similar to fibroadenoma but more stromal overgrowth, infilitrating margins, and greater cellularity, mitotic rate and nuclear pleomorphism
Treat - excision with wide margins to prevent local recurrence
Note - most are low-grade and indolent but can be high grade and aggressive with features of soft tissue sarcoma

Front 26

Fibrocystic changes (nonproliferative breast changes)

Back 26

Epi - esp in 4th and 5th decades
Px - nodularity or lumpy bumpy changes usually without a dominant mass. May be asymptomatic, but frequent premenstrual tenderness and nodularity abating with menses.
Histo - Cyst formation, freuently with apocrine metaplasa, fibrosis. Increased # acinar units per lobule (adenosis).
Note - have to exclude carcinoma. This is grossly present in 20% and histologically in 59% - w/n spectrum of normal breast.

Front 27

Proliferative breast disease without atypia

Back 27

Px - rarely masses, but can mammographic abnormality or an incidental finding in biopsy.
Histo - moderate or florid epithelial hyperplasia (>4 cell layers). Sclerosing adenosis (2x normal acini in terminal duct). Complex sclerosing lesions (radial scar), papillomas (peripheral small ducts), fibroadenoma with complex features.
Note - 1.5 - 2x risk of invasive breast carcinoma

Front 28

Proliferative breast disease With Atypia

Back 28

Gross has two types:
1) Atypical ductal hyperplasia (ADH) is similar to ductal carcinoma in situ but is quantitatively or qualitatively insufficient.
2) Atypical lobular hyperplasia (ALH) similar to lobular carcinoma in situ but does not fill or distend >50% of acini within a lobule.
Clinical: ADH presents in 5-17% of biopsies for clinical calcifications, densities, or palpable masses. ALH is always an incidental finding (no mass or density). 4-5x risk of invasive breast cancer!

Front 29

Incidence and Epi of Carcinoma of the Female breast

Back 29

Incidence:
- most common non-skin malignancy in females. 1 in 8 chance of developing breast cancer for women living to age 90.
Risk factors - age (rare before 25, avg. age 64), early menarche, age at first live birth (risk if older or no kids), 1st degree rel with bCA, prior breast biopsy with atypical hyperplasia, race (White>Black>Asian>hispanic), estrogen exposure, breast densitym radiation exposure, carcinoma of other breast or endometrium, geography, diet, obesity, excerise, breast-feeding etc.
Note - virtually all adenocarcinomas

Front 30

Ductal Carcinoma in situ

Back 30

Several patterns - cribiform, solid, papillary, micropapillary, comedo
Epi - 15-30% of all carcinomas. But ductal type is 80% of CIS.
Malignant population of cells limited to ducts and lobules by basement membrane.
Risk - 8-10X for invasive carcinoma

Front 31

Lobular Carcinoma in Situ

Back 31

20% of CIS is lobular type. Always incidental finding bc there are no calcifications, density, or mass
Histo - acinar units filled and distended by non-cohesive small cells.
Epi - occurs in younger women (80-90% premenopausal)
Risk - 8-10X for invasive carcinoma

Front 32

Paget's disease of nipple

Back 32

Epi - rare 1-2%
Gross - unilateral, red eruption with scale crust
Patho - caused by DCIS cells extending from duct system into nipple skin. 50-60% have underlying palpable mass with invasive poorly differentiated cancer, overexpressing her2/neu receptor

Front 33

Infiltrating Ductal Carcinoma NST (stats, px, histo, genetic patterns)

Back 33

Epi - 79% of total breast cancers
Px - present as palpable mass of mammo density. Mets usually to regional lymph nodes, lung, pleura, bone
Gross - firm, irregular borders, gritty, and fibrotic with retraction
Histo - malignant cells forming tubules,nests, cords and sheets in a fibrotic stroma, pattern and cell pelomorphism determines grade.
Genetics - Hormone receptor status varies, Her2/neu varies. 5 major gene expression patterns:
1) Luminal A (40-55% of NST): ER positive, Her2/neu neg. well to moderate differentiated, slow-growing. respond to hormone therapy but usually not chemo
2) Luminal B (15-20%): ER positive but also frequently Her2/neu positive (triple+). Usually higher grade and more proliferative. More likely wth +LN. response to chemo
3) Normal breast expression-like (6-10%): Gene expression similar to normal. ER+ and Her2/neu negative. well-differentiated
4) Basal-like (13-25%): Triple neg (ER-/PR-/her2neu-). +/- BRCA1 mutations/ethnicity/young. High grade, high proliferation rate, frequent mets, usually aggressive with poor prognosis but a subset is sensitive to chemo.
5) Her2/neu positive (7-12 of NST%): overexpress Her/neu. Poorly differentiated and high proliferation rate. frequent brain mets. Respond to trantuzumab (but doesnt cross bbb)

Front 34

Lobular carcinoma

Back 34

Epi - 10% of all breast cancers
Px - mass/density or in 25% cases as vague thickening. Mets to LN, but also to peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries and uterus
Gross: most hard with irregular margin but less tissue fibrosis
Histo: Single file poorly cohesive (E-cadherin neg) tumor cells frequently infiltrating around ductal structures. Genetics: Usually ER/PR positive and do not overexpress Her2/neu

Front 35

Medullary Carcinoma

Back 35

Epi - 2% of total
Px/Gross - well-circumscribed more yielding mass, fleshy, softer, frequently with rapid growth.
Histo - pushing border composed of solid, syncytium-like sheets of large pleomorphic cells with lymphoplasmacytic infiltrate within and surrounding tumor.
Genetics - does not overexpress Her2/neu, ER/PR negative. Common in BRCA1 gene mutations and 67% of all medullary carcinomas have hypermethylation of BRCA1 promoter
Prognosis - slightly better than NST, LN usually negative

Front 36

Mucinous (Colloid) Carcinoma

Back 36

Epi - 1-6% of all breat carcinoams, olde rpatients
Px - circumscribed, slow growing, soft mass. very soft grossy with blue-gray gelatin-like consistency
Histo - clusters and islands of cells floating w/n lakes of mucin pushing into stroma.
Genetics - usually hormone receptor positive. More common in BRCA1 mutations and BRCA1 promoter hypermethylation in 55% of non-germ line mutations.
Prognosis - slightly better that NST

Front 37

Tubular Carcinoma

Back 37

Epi - Up to 10% of all carcinomas <1 cm. Usually detected on mammo
Gross - 10-56% mutlifocal in one breast and 9-38% bilateral.
Histo - exclusive well-formed tubules without myoepithelial cell layer. LCIS frequently present. Well differentiated.
Genetics - >95% hormone receptor positive.
Prognosis - excellent. axillary mets in <10%

Front 38

Invasive Papillary Carcinoma

Back 38

<1% of total. Clinical presentation same as NST but better prognosis

Front 39

Inflammatory Carcinoma presentation

Back 39

Swollen, erythematous breast with skin thickening (peau de l'orange) that mimics infection. Symptoms caused by tumor invasion of dermal lymphatics. Presentation can delay diagnosis. Course is aggressive with usual axillary mets at diagnosis and poor prognosis.

Front 40

Male gynecomastia and cancer

Back 40

Px - unilateral or bilaterl subareolar enlargement due to hyperestrinism
Histo - proliferation of dense collagenous connective tissue with marked micropapillary hyperplasia of duct linings. Not assoc with cancer.

Carcinoma - Rare, <1:100 frequency of female cancer. Usually aggressive bc presents t higer stae. Similar risk factors as women and increased in men with BRCA2 gene mutation

Front 41

Endocervical polyp

Back 41

benign inflammatory tumors that arise within the
endocervical canal. They are relatively common and can be seen in 2% to 5% of adult
women. They consist of a loose fibromyxomatous stroma lined by endocervical epithelium and range in size from small sessile lesions to large 5 cm pedunculated masses. Dilated, mucus-secreting endocervical glands, inflammation, and squamous
metaplasia are common findings. They may present with “spotting” and bleeding raising
suspicion of some more serious lesions. Treatment: surgical removal or endocervical curettage

Front 42

CIN I, II, III

Back 42

CNI I. Histologically indistinguishable from condyloma
acuminatum. Characterized by viral cytopathic changes in the superficial layers of the epithelium (koilocytotic atypia). Associated with low-risk HPV.
CNI II. Characterized by the appearance of dysplastic
cells in the lower layers of the epithelium (increased
nuclear to cytoplasmic ratio, hyperchromasia, increased mitotic activity, loss of polarity). Associated with high-risk HPV.
CNI III. Characterized by full thickness dysplasia and
minimal or no surface maturation. Associated with highrisk HPV. Highest risk of progression to invasive
carcinoma.
CIN is characterized by aceto-white lesions (white
patches after the application of acetic acetic), and abnormal vascular patterns (mosaic
or punctuation patterns). Any abnormalities should be confirmed by histologic
examination. In challenging cases, immunohistochemical stains for cyclin E, Ki67, and
p16INK4 may help distinguish precancerous lesions from reactive epithelial changes.
The treatment of CIN depends on the stage of the lesion and includes follow-up with
Papanicolau smear for CIN I, and cryotherapy, laser, electric loop excision procedure
(LEEP), and cone excision for CNI II and III.

Front 43

Bartholin Cyst

Back 43

Acute infection of the Bartholin gland can lead to adenitis (acute inflammation of the
gland) and abscess formation. Bartholin cysts are relatively common, can occur at any
age, and result from obstruction of the gland duct, which is usually secondary to
infection. These cysts can become quite large (up to 5 cm) resulting in significant local
discomfort and pain. The treatment is surgical removal or marsupialization of the cyst

Front 44

Vulvar vestibulitis

Back 44

s characterized by
inflammation of the surface mucosa and submucosal vestibular glands, and formation of
small superficial ulcers. This condition leads to chronic, recurrent, exquisite pain. The
cause is unknown and the treatment consists of surgical excision of the inflamed
mucosa.

Front 45

Lichen Sclerosus

Back 45

o atrophy, fibrosis, and
scarring of the vulva. On physical examination, the vulvar skin is pale gray and
parchment-like. On long-standing cases, the labia become atrophied, and the introitus
narrowed. Microscopically, there is atrophy of the epidermis, hydropic degeneration of
the basal cell layer, severe fibrosis of the dermis, and band-like monoclonal lymphocytic
infiltration of the lower dermis. Although the pathogenesis is not completely understood,
many of its features suggest an autoimmune origin. This disorder can occur at any age,
but has a predilection for postmenopausal women. It tends to be insidious and
progressive. It is not considered a premalignant condition, but it is associated with a
greater risk of subsequent carcinoma (1% to 4%).

Front 46

Lichen Simplex Chronicus

Back 46

Lichen simplex chronicus, formerly known as hyperplastic dystrophy, is a nonspecific
condition that manifests clinically as leukoplakia and it is the result of rubbing or
scratching the vulvar skin to relieve pruritus. Its causes include infections (tinea,
candida, etc.), mucosal irritation due to chemical exposure, and other causes of
pruritus. Histologically, this disorder is characterized by acanthosis (thickening of the
squamous epithelium), hyperkeratosis, increased mitotic activity, and variable leukocytic
infiltration of the dermis. Similar to lichen sclerosus, lichen simplex chronicus is not
considered a premalignant lesion, but it is associated to a greater risk of carcinoma.

Front 47

Papillary Hydradenoma

Back 47

This tumor is histologically identical to the intraductal papilloma of the breast. It
presents as a well-circumscribed nodule in the labia majora or interlabial folds.
Because of its tendency to ulcerate it may be confused clinically with a carcinoma.
Microscopically, it is characterized by tubular ducts lined by nonciliated columnar cells
surrounded by a layer of myoepithelial cells.

Front 48

Condyloma Acuminata

Back 48

Condylomata acuminata are sexually transmitted, papillomavirus-induced, benign
tumors that have a characteristic verrucous gross appearance. They involve perineal,
vulvar, and perianal regions, and are usually multiple. Histologically, they consist of a
branching, tree-like proliferation of stratified squamous epithelium supported by a
fibrous stroma. The squamous epithelium shows acanthosis, parakeratosis,
hyperkeratosis, and viral cytopathic effect (koilocytotic atypia). Koilocytes are virally
infected cells characterized by hyperchromatic, raisinoid nuclei, and perinuclear
vacuolization or clearing of the cytoplasm. Human papillomavirus (HPV) is the causal
agent of condyloma acuminatum, with HPV 6 and HPV11 being the most commonly ZHENG: Diseases of Vulva Vagina and Cervix 6
implicated types. In the immunocompetent host, this tumor usually resolves
spontaneously. This entity is a marker for sexually transmitted diseases and is not
considered a premalignant lesion.

Front 49

Categories of Vulvar Carcinoma

Back 49

Lesions associated with high-risk HPV (types16, 18
and others). This variety of carcinoma is usually coexists or is preceded by classic VIN. These tumors can be exophytic or indurated, and are frequently ulcerated. Microscopically, they are characterized by an invasive growth pattern, and can be well-differentiated (warty) or poorly-differentiated (basaloid).
2)Lesions associated with lichen sclerosus/squamous
hyperplasia. The etiology is unclear and some of these lesions have been associated with accumulation of p53 protein. They occur as rapidly growing nodules in a background of inflammation. Microscopically, they are characterized by prominent keratinization.

Front 50

Paget disease of the vulva

Back 50

Paget disease of the vulva is a rare condition that is similar, grossly and
microscopically, to its breast counterpart. It usually presents as a pruritic, red, sharply
demarcated, geographic lesion usually located on the labia majora. Occasionally, a
palpable submucosal thickening or tumor is identified at the time of diagnosis.
Microscopic examination reveals large neoplastic cells within the epidermis and its appendages. The tumor cells are surrounded by a clear halo and have relatively abundant, finely granular, pale cytoplasm that stains with mucin stains. In sharp
contrast to Paget disease of the nipple, extramammary Paget is almost always confined to the epidermis and its appendages, and is rarely associated with an underlying tumor.
Staining: Keratin +, PAS +, CK7 +, HMB45 -, S100 -

Front 51

Malignant melanoma of vulva

Back 51

Malignant melanoma of the vulva is a rare lesion that accounts for less than 5% of all
malignant vulvar cancers and 2% of all melanomas in women. Most cases occur in the
sixth of seventh decades of life. The microscopic features and clinical behavior are
similar to those of melanomas located elsewhere. Grossly and microscopically, vulvar
melanoma may resemble Paget disease. The 5-year survival rate is less than 32% and
the prognosis is closely linked to the depth of invasion of the tumor. (Staining: keratin neg, s100 Positive, PAS neg)

Front 52

Embryonal Rhabdomysarcoma

Back 52

Embryonal rhabsomyosarcoma, also known as sarcoma botryoides, is an uncommon
vaginal tumor that presents during infancy and early childhood. On gross examination,
the lesion has a characteristic appearance: semi translucent polypoid masses that
resemble clusters of grapes (hence the term botryoides that means grapelike). The
tumor is composed of malignant rhabdomyoblasts lying within a myxomatous stroma.
There is a characteristic crowding of the neoplastic cells immediately beneath the
vaginal epithelium, forming the so-called cambium layer. Because of the presence of
inflammatory cells, these lesions are sometimes mistaken for inflammatory
pseudopolyps. These lesions invade locally and cause death by invasion into the
adjacent organs and peritoneal cavity. Conservative resection and chemotherapy are
the treatment of choice in patients diagnosed early.

Front 53

Adenocarcinoma of the vagina

Back 53

Adenocarcinoma of the vagina is a rare neoplasm. Patients whose mothers received
diethylstilbestrol (DES) during pregnancy are at an increased risk of developing clear
cell adenocarcinoma. Most of these cases occur during the second decade of life. The
tumors are usually located on the anterior wall of upper third of the vagina, and range in
size from a 0.2 to 10 cm. Microscopically, they are characterized by vacuolated,
glycogen-containing glandular cells. Vaginal adenosis appears to be the precursor
lesion and occurs in 35% to 90% of patients with history of antenatal exposure to DES.

Front 54

Leiomyosarcoma

Back 54

- bulky, fleshy SINGLE mass
- necrotic with hemorrhage
- age 40-60 yrs, but postmenopause
- Cellular atypia
- arises de novo
- Mets via hematological, intra-abdominal
- 5 Year survival is 40%. Worse if anaplastic type (10-15%)

Front 55

Endometrial hyperplasia

Back 55

Def - excessive gowth of endometrial tissue (glands and stroma) with tissue architectural alterations.
Epi - occurs in later repro years and early post-menopausal.
Causes - prolonged estrogen stimulation of the endometrium (like in PCOS, or HRT, estrogen sec tumor)
Symptoms - abnormal bleeding
Classifications: simple (more glands, irregular), complex (more dense packed glands with marked irregular size/shape), with or without atypia (nuc enlargement, pleomorphism, prominent nucleoli, coarse chromatin, loss of cell polarity).
Treatment - remove source of estrogen, curettage, prog suppression, hysterectomy
Clinical course - Transfusions, hormones
Risk - depending on type risk for adenocarcinoma type 1.

Front 56

Endometrial carcinoma type I (endometriod)

Back 56

Estrogen-driven with endometrioid histo (like normal but not quite endometrium). Type I is 80% of endometrial CA.
Epi - Older than40's, mainly 50-60s.
Associations: early menarche, late menopause, unopposed HRT, obesity, diabetes, htn, infertility.
Protective associations: OCPS with progesterone, breast feeding, full term pregnancy, combined HRT< excersie, smoking
SYmptoms - post-menopausal bleeding

Front 57

Endometrial carcinoma type II

Back 57

Non-estrogen driven. 15-20% of endometrial carcinoma. Occurs in older women (60-70s). Serous, clear cell, and carcinosarcoma. Usually nuclear grade 3 tumors (nuclei with dramatic atypia and pleomorphism).
Uterus remains small. background atrophic endometrium
Histo - papillary structure lined by highly
pleomorphic cells with abnormal hobnailed
nuclei.

Front 58

Carcinosarcoma (mixed mullerian malignancy)

Back 58

Definition: endometrial adenocarcinoma in which there is malignant stromal differentiation into BOTH epithelial and mesenchymal (muscle, cartilage, bone) components. Both components are believed to be from the same cell.
Cause - not related to estrogen.
Epi - postmenopausal women
Morphology - large mass, often beyond uterus at diangosis. Histo - adenocarcinoma with sarcoma elements.,
Course: determined by depth of invasion and stage. Carcinoma part metastasized more freq than sarcomatous part.

Front 59

Placental hormones (and what they do)

Back 59

a. Human chorionic gonadotropin maintains the corpus luteum (secretes
progesterone) until the placenta can synthesize adequate progesterone to
maintain the pregnancy.
b. Human placental lactogen has anti –insulin properties and changes the
metabolic state of the mother to increase availability of nutrients to fetus. Its
major effect is to raise maternal blood glucose levels.
c. Estrogen. Estrogen enhances uptake of LDL cholesterol for placental
steroid production, increases uteroplacental blood flow, and increases
prolactin synthesis. Estrogen may also be important for placental
angiogenesis, thus boosting fetoplacental nutrient transport.
d. Progesterone stimulates maternal food intake and suppresses maternal
cell-mediated immunity to prevent rejection of the fetus

Front 60

Why can endometriosis lead to infertility?

Back 60

40% of endometriosis --> infertility
-pelvic adhesions
- functional abnormalities of endometrium and tubes
- production of substances that interfere with normal ovulation (cytokines, growth factors)
-inc levels of anti-endometrial antibodies

Front 61

Alcohol (and other recreational drugs) as a teratogen

Back 61

Produces Fetal Alcohol Syndrome
o PofM:
 Growth retardation
 Developmental/behavioral abnormalities
 Facial feature abnormalities:
 Microcephaly
 Microphthalmia
 Short nose
 Smooth philtrum
 Thin upper lip
o Most preventable cause of mental retardation in the world!
o Timing
 10% risk of FAS to those offspring of chronic alcoholic women
 30% risk of some observable adverse effects – not full FAS

Other: Many agents are not associated with malformations but can have neurobehavioral effects instead:
Marijuana, LSD, heroin, barbiturates, and stimulants

Front 62

Pediatric vs. Adult patient drug selection and therapy

Back 62

o Age - pharmokinetic properties change with age.
o Body Size - dose for mg/kg/dose
o Disease
o Organ function

Drug conc same for adult and kids for same disease. But some drugs are not for kids (Aspirin --> reye's syndrome). Off label drug use in kids is common.

Front 63

Peds factors for route of administration

Back 63

Delivery:
1) Oral route: pH at birth = 6-8 but drops to 1-3 within 24hrs (problem with absorption for preemies bc ph stays high). Active and passive transport develop fully at 4 months
 Effect of low acid secretion (high pH):
o INCREASED concentration of weak bases (inc absorption of penicillin g) and acid-labile medications
o DECREASED concentration of weak acid medication due to increased ionization (dec absorption of phenobarbital)
- Gastric emptying times: DELAYED in premature infants. Results in increased contact time in the GI mucosa = increased amount absorbed! Reach adult values in 6-8 months
- Pancreatic exocrine and biliary function Reduced and variable in neonates – 50%. Reach adult values by age 5. Results in decreased bioavailability of drugs requirinh solubilization or intraluminal hydrolysis like prodrugs (erthyromycin)
2) Topical/percutaneous admin - absorption inc in preemies bc of thinner stratum corneum, inc skin perfusion, and inc body surface to weight ratio. use the smallest amt possible
3) IM - variable perfusion not ideal bc of less muscle
4) Rectal - variable absorption, not ideal (diazepam gel, acetaminophen, glycerin)

Other considerations:
1) Intravenous formulations: Some medications may require further dilution to measure smaller doses/ To reduce irritation. Some medication may need to be
concentrated for fluid-restricted patients like preemies with cardiac probs

Front 64

Peds - volume of distribution

Back 64

1) Extracellular fluid (ECF) vs total body water (TBW): Neonates and Infants have increased fluid = higher Vd for WATER SOLUBLE drugs = need a higher dose to get same therapeutic concentration (Fluid then decreases with age).
2) Protein binding: Binding protein determines how much unbound/active fraction is available Neonates and infants Have a LOWER normal range of serum albumin = lower dose for LIPID SOLUBLE drugs
3) Body fat is LOWEST in neonates, increases with age . However Vd for infants vs adults is fairly similar for lipophilic medications. In theory, premature and infants have lower Vd = lower doses for lipid soluble
drugs
4) Blood-brain barrier: NOT well developed in premature neonates and infants compared to older children and adults --> INCREASED distribution of lipid soluble medications into CNS! Some lipid-soluble compounds can reach 10-30x infant serum amounts!
5) Protein Binding - Neonates and infants have a lower normal range for serum albumin. Decreased protein binding of drugs resulting in increased unbound fraction (ex: phenyton is 20% unbound in neonates vs. 10% in adults)

Front 65

Peds - metabolism/hepatic

Back 65

Slow Phase I reaction systems: Oxidation, CYP P450, Alcohol dehydrogenase. NEED TO WATCH doses closely for patients < 6mo for drugs given metabolized by these systems (Include elixir forms of medications that contain some alcohol!) Peak rate is 4-6
o Phase II reaction systems: Matures at different rates during 1st year of life
- Sulfation is well-developed in newborns
- Glucuronidation and acetylation is underdeveloped in neonates and infants. Takes 1-2 years to get to adult level
o Can cause grey baby syndrome with chloramphenicol usage
o Acetaminophen is okay due to sulfation

- Neonates and infants Require LOWER mg/kg/day doses of hepatically metabolized drugs
- Young children – 1-9yrs Actually have the MOST rapid hepatic drug metabolism = higher does for some
medications. Peak for hep metab is 4-6.
- Growth to puberty: Hepatic metabolism and clearance slows significantly to adult level

Front 66

Peds - elimination/clearance

Back 66

1) Neonates and Infants: Renal clearance is SLOWEST in premature neonates --> Results in LONGER dosing intervals for certain medication
2) Children and adolescents have the MOST rapid drug elimination of all age groups when adjusted for body size (ages 3-12). Therefore require more frequent dosing (ex. vancomycin). Clearance similar to adult with older age
o Renal drug clearance varies widely in size and therefore normalized based on body size = ml/min/m^2. Mainly measured by glomerular filtration = estimated from the creatinine clearance. GFR increases quickly in the 1st month of life. Continues to increased during 1st 4 months and then stabilizes
 Cockroft and Gault (C-G) equation ONLY used in patients > 18 years. NOT FOR CHILDREN
o Based on gender, age, ideal body weight, and SCr

- FOR KIDS: Schwartz equation (6 mo - 21 yrs)
o Based on age/gender constant, length, and SCr
- Traub-Johnson equation: Based on height and SCr with a constant of 0.48, For patients 1-18 yrs old
for both gives rate as ml/min/1.73m^2

Front 67

Common meds errors

Back 67

Errors can easily occur with pediatric medications:
 Accuracy of body weight
o CHECK kg vs. lb and g vs. kg
 Decimal and order interpretation
o Trailing zeros – 1.0mg vs 1 mg
o Missing leading zeros – 0.1mg vs .1mg
 Calculations:
o Dose per kilogram errors
o 10 fold decimal/calculation errors
o Mg vs. mcg or mg/dose vs mg/d
o Dosing errors of combination products
 Look-alike durgs
o Epinephrine strength – 1:1000 vs. 1:10K
o Heparin strength
o Similar appearing labels/units – heparin vs insulin
 How to prevent/minimize errors?
o Simplify medication use
o Order standardized/correct concentrations and doses
o Use bar codes
o Standardize infusion equipment
o Standardize drug concentrations for high risk medications
o Check medications at point of care and monitor therapy

Front 68

Pharmacodynamics peds diferences

Back 68

1) PK affects PD, for example with Safety
Example: slower clearance of gentamicin leading to increased incidence of nephrotoxicity with inappropriate dose
2) Efficacy: Receptor action in pediatric patients may not be the same as adults. Example: Tricyclic antidepressants and major depressive disorder

Front 69

Complete hydatidiform mole

Back 69

Complete Mole:
 Considered the “classic mole”
 Find swelling of ALL or most chorionic villi + DIFFUSE trophoblastic hyperplasia
 KEY is that it’s due to DIPLOID karyotype – 46 XX (>90% of cases)
 Crazy thing is all chromosomes are of PATERNAL derivation
Over proliferation of syncytialtrophoblastic cells = overproduction of Beta-hCG
 Grossly:
 Mass of thin-walled, friable, semi-translucent, grape like structures filling the
uterine cavity
 NO fetal parts are found!
Micro:
 Hydropic swelling of choronic villi
 Diffuse hyperplasia
 Insufficient or ABSENT development of vascular elements within the villi
Malignancy Potential:
 10% evolve into invasive mole
 2% or less evolve into choriocarcinoma

Front 70

Partial hydatidiform mole

Back 70

only partially involves the chorionic villi
 Find cystic degeneration and FOCAL trophoblastic hyperplasia
 KEY is that it occurs in triploid karyotypes – 69 XXX or 69 XXY, sometimes tetraploid – 92
XXXY)
 Grossly:
 Similar findings as classic moles but LESS pronounced
 Embryo is viable for weeks = formation of FETAL parts can be found! Rarely evolve into more aggressive lesions.
Clinical: not as bleeding, uterine size +/- enlargement,
Treatment:
 Thorough uterine curettage
 Anticancer medicine or hysterectomy
 Follow-up with Beta-hCG levels to monitor progress

Front 71

Invasive mole

Back 71

Characterized as the PERSISTANCE of a molar pregnancy even AFTER evacuation
 Find myometrial invasion by hydropic chorionic villi.
There is continued proliferation of trophoblastic epithelium
 BENIGN in nature:
o However locally invades with potential to perforate the uterine wall (rare)
 Luckily HIGHLY responsive to chemotherapy
 Complications:
o Perforation of the uterine wall
o Invasion of the parametrial structures
o Vascular invasion
o Tumor embolism to distant sites – NOT a true metastasis
 Clinically:
o Recurrent vaginal bleeding
o Irregular uterine enlargement
o Persistently elevated Beta-hCG
o Varying degrees of luteinization of the ovaries
o Hemorrhagic complication/rupture of uterine wall can be LIFE-THREATENING

Front 72

Choriocarcinoma

Back 72

This is a MALIGNANT neoplasm of the chorionic epithelium
 Tends to be a RARE malignancy in the US:
o 1/20-30K pregnancies!
o 50% occurs in patients with history of GTD
o 25% follow an abortion
o 22% after an apparently normal pregnancy
o RARELY occurs in ectopic pregnancy or teratomas
 Characteristics:
o HIGHLY aggressive
o Rapidly invasive with wide metastatic spread
o Uniformly FATAL if left untreated
o EXTREMELY sensitive to chemotherapy
 HUGE game changer as before cancer tends to be so rapidly invasive that we don’t catch it in time before metastasis
 Allows for 100% remission rates!
 Risk factors:
o Maternal age > 35 years
o Increasing parity
o Prolonged use of oral contraception (> 5yrs)
o Lower endogenous estrogen levels
o Women who are:
 Asian
 American Indian
 African American
 Grossly:
o Soft, fleshy, yellow-white tumor mass that INVADES the uterine wall
o Extensive foci of hemorrhage, cystic degeneration, and necrosis
 Micro:
o Neoplastic proliferation of BOTH cytotrophoblast and syncytiotrophoblast WITHOUT chorionic
villi
o
 Clinically:
o Irregular, bloody, foul-smelling vaginal discharge
o Occurs after normal pregnancy, miscarriage, or in a patient with history of hydatidiform mole
o Widespread metastasis is constant find at time of diagnosis – preferred sites:
 Lungs – 50%
 Vagina – 30-40%
 Brain, liver, and kidney
 Treatment:
o Depends on stage of tumor
o Evacuation of uterine contents
o Hysterectomy – rarely done
o Chemotherapy – most efficient
o Follow up with beta-hCG levels

Front 73

Placental site trophoblastic tumor

Back 73

Accounts for < 2% of GTD
 Characterized by proliferation of INTERMEDIATE trophoblasts present at the residual placental site
 50% of cases – after normal pregnancy
 50% of cases – after abortion or a hydatidiform mole
 Clinically:
o Beta-hCG levels may be high, but these cell types tend to secrete human placental lactogen
(HPL)
o
 Micro:
o Invasion of myometrium by neoplastic population of mononuclear polygonal cells
Prognosis:
o Depends of stage and time interval between preceding pregnancy and diagnosis
o MOST cases = good response to treatment (chemotherapy)
 10% of patients develop disseminated disease = DEATH

Front 74

Follicular cyst

Back 74

Arise in unruptured graafian follicles or follicles that ruptured but immediately sealed
o EXTREMELY common
o Cysts that exceed 2cm = follicular cysts
 Those < 2cm = cystic follicle
o Characteristics:
 Filled with clear serious fluid
 Lined by smooth and glistening membrane
 Composed of granulosa and outer theca cells
 Luteinized theca interna cells

o Large cysts:
 Can cause pelvic pain and abnormal bleeding
o Diagnosis:
 Physical examination
 Ultrasound

Front 75

Luteal Cyst

Back 75

Normal cysts in the ovary that usually regress spontaneously
o However for some reason they persist
o Grossly:
 Lined by a layer of luteinized granulosa and theca cells = bright golden yellow color to
lesion
 Fluid content is often bloody
 Usually single
 Rarely > 6cm

o Advanced lesions = difficult to distinguish from endometriotic cysts
o Clinically:
 Complain of pelvic pain
 Or dysfunctional uterine bleeding
o Rare complication:
 Rupture leading to erroneous diagnosis of ruptured ectopic pregnancy

Front 76

PCOS

Back 76

Characterized by the presence of numerous cystic follicles within the ovary

o Classic clinical picture:
 Stein-Leventhal syndrome = PCOS
 Find persistent anovulation, amenorrhea, obesity, hirsutism, and rarely virilism
o PCO does NOT = PCOS
o Pathogenesis:
 Not completely understood
 However thought to be related to elevated LH levels
 Results in abnormal regulation of enzymes used to synthesize androgens
o Associations:
 PCO and insulin resistance = DM in many patients
 Increases cardiovascular disease
 Also increase risk of endometrial cancer Type I
 Due to overproduction of estrogen by MANY cystic follicles in the follicular
phase of the cycle
o Micro:
 Due to proliferation of granulosa and theca intera cells, oddly there is increased
production of Inhibin by Theca cell > Granulosa cells

o Treatment:
 Oral contraceptives
 Induction of ovulation
 Wedge ovarian resection – rarely used
 Screening for diabetes, hyperlipidemia, and hypertension

Front 77

Stromal hyperthecosis

Back 77

uniform enlargement of the ovaries (up to 7cm) have a diffusely white to tan appearance
on cross section

o Micro:
 STROMAL hypercellularity
 Can be 2 types:
 Stromal hyperplasia – NO luteinized theca cells
 Stromal hyperthecosis – with luteinized theca cells

o Occurs most commonly in POSTMENOPAUSAL women
 Also associated with PCO in younger patients
o Clinically:
 Similar to PCO disease with virilization being a striking feature
 Elevated LH, androgen levels, and DM etc)

o Treatment:
 Surgical resection of ovaries

Front 78

Suppurative vs. tuberculous salpingitis (and why it can lead to infertility)

Back 78

Suppurative Slapingitis:
o This is an acute inflammatory process involving the fallopian tubes
o Any pyogenic microorganism can be causal agent, Neisseria gonorrheae = 60% of cases
 Causes pelvic inflammatory disease (PID)
 Important cause of infertility due to scarring of the tubes = inhibition of
fertilization
 Also commonly caused by Chlamydia
o Micro:
 Edema and acute inflammation of tubal wall + dense fibrinopurulent infiltrate within
lumen = abscess

 Tuberculous Salpingitis:
o EXTREMELY rare in the US = < 2% of cases
o In areas of the world where TB is more prevalent = more common condition
o Micro:
 Classic necrotizing granulomas seen in tuberculosis


Front 79

Ectopic pregnancy ( most common anatomical sites,
predisposing factors and possible pathophysiological outcomes.)

Back 79

Occurs when implantation of the fetus occurs at any site OTHER than the uterine cavity
 Most common place is within the fallopian tubes (90%)
o Ovaries, peritoneal cavity, and intrauterine portion of the fallopian tube are other locations
o At the site of implantation, fertilized egg undergoes usual development = formation of placenta,
amniotic sac, and fetus
 Epidemiology:
o Occurs 1/150 pregnancies
o Predisposing factors:
 PID with chronic salpingitis – 35-50% of cases
 Peritubal adhesions – endometriosis, appendicitis, previous surgery
 Intrauterine devices
o Interestingly, 50% of cases occur in apparently NORMAL tubes!
 Pathophysiology:
o Placental tissue will continue to invade wall of the tube = can lead to tubal rupture and
intraperitoneal hemorrhage = hemoperitoneum!
o Other cases – partial separation of the placenta without rupture of the tube = intratubal
hemorrhage or hematosalpinx
o Other outcomes – spontaneous regression with resorption of the pregnancy
 Micro:
o All histologic elements of a normal pregnancy can be found
 Clinically:
o EP with tubal rupture:
 ACUTE ABDOMEN = medical emergency
 Severe abdominal pain that can progress to rapid fall into shock-like state
 History of missed menstrual cycle
 History of PID
 Treatment:
o Diagnosis:
 hCG levels
 U/S studies
 Laparoscopy
o Treatment:
 Medical – methotrexate
 Surgical – salpingectomy

Front 80

Paratubal cyst

Back 80

These are minute translucent cysts filled with clear fluid (<2.0cm)
 Believed to arise from remnants of the mullerian duct = no clinical significance
 Those larger cysts found near the fimbria or the broad ligament = hydatids of Morgagni

Front 81

Adenomatoid tumor

Back 81

benign tumor are small nodules occurring in the subserosa o the tube and occasionally in the mesosalpinx. (also in testes and epididymus)

Front 82

Primary adenocarcinoma of fallopian tube

Back 82

Primary - the bulk of the tumor must be in the fallopian tube. limen of the tube has to be involved, and the lesion has to arise from the tubal mucosa. Microscopically, tubal adenocarcinoma usually exhibits a papillary architecture with tubal differentiation.
Clinical: abnormal dischage (watery discharge in elderly woman), bleeding. sometimes abnormal pap smear. SOme of these lesions carry BRCA germlike mutations.

Front 83

Theory - fallopian tube as source for ovarian and peritoneal serous carcinomas

Back 83

Starts in tubes as a precancerous lesion – dysplasia or tubal intraepithelial carcinoma
 Then with sloughing off or rubbing against ovaries, malignant cells get STUCK to ovary = secondary ovarian cancer
KEY is that tubal fimbria FREQUENTLY contain in situ serious carcinomas with a alternation of p53 = signature find for tubal origin
 Cells either rub off onto ovaries, or fall from fimbria into peritoneal cavity

Front 84

Hormonal influences in PMS/PMDD

Back 84

- normal hormonal cycling leads to reduced levels of serotonin in late luteal phase (triggering symps of irritability, dysphoria, carb craving). Acute depletion of tryptophan too (sero precursor)
- low GABA levels low in late luteal phase
- More SHBH --> % of free estradiol much lower, esp in luteal phase
- P4 (progesterone) rises in luteal phase. So is it the relative E2/P4 balance contributing??!
- low allopregnanolone

Front 85

Reqs. for diagnosing PMDD

Back 85

1-4 of the following symptoms
Depressed mood or dysphoria, anxiety or tension, affective lability, irritability
And at least 4 of the following (dec interest in usual activities, concentration difficulties, marked lack of enregy, change in appetite, sleep change, feeling overwhelmed, physical symptoms like breast tenderness, bloating).
Symptoms must interfere withw ork, school, usual activities, or relationships. Can't be an exacerbation of another disoerder. All criteria must be confirmed by daily ratings for at least 2 consecutive cycles.

symptoms MUST begin in late luteal phase and dissipate by the end of menstrual flow.

Front 86

Early transition vs. late transition (MP)

Back 86

Early - increased variability mc length. greater than a difference of 7 days from cycle to cycle. FSH increases, inhibin decreased.
Late - skipping of meses in which the typical mc length is doubled or longer. Rising FSH. In general FSH > 20 IU/L and estradiol lower than 60 pg/ml indicate reduced ovarian function.

Hot flashes peak within the year before final period and on average continue through 3 years after.

Front 87

0-2 months (motor, social, adaptive, problem-solving, language)

Back 87

GM: Can lift head briefly at birth.
By 2 months, can lift up chest
FM: Hands are tightly fisted at birth. By 2 months hands are >50 unfisted
visual fixation, auditory
VS: alerting at birth, tracks horizontally at 1 month,
vertically at 2 months
Language: R: alerts to sounds at birth, regards speaker and socially smiles by 2 mo.
E: throaty noises, cries at birth. coos by 2 months

Front 88

6 months (motor, social, adaptive, problem-solving, language)

Back 88

GM: Rolls both ways starting prone to supine at 4
months and progressing supine to prone at 5 months. At 6 months, sits propped,
FM: Starts raking using entire hand at 4 months (ulnar)
transitions to raking with the radial aspect of the hand by 6 months, transfers objects hand to hand at 6
months.
Develops stranger awareness: prefers to be with family members, but will allow others to hold or comfort, especially if a family member is nearby
Emerging object permanence: Looks to floor when drops toy, attains partially hidden toy, removes cloth covering face
E: sing-song vocalizations and babbling by 6 months
RL: Orients to sounds by looking directly towards the location of the sound (little seeking)

Front 89

12 (motor, social, adaptive, problem-solving, language)

Back 89

GM: Cruises at 10 months, takes a few step at 12 months
FM: Immature pincer at 9-
10 months. By 12 months, mature
pincer, release of cube into cup, attempts release of
pellet
Proto-imperative point (A child points to an item to
obtain it). Cooperates with dressing
Recognizes patterns: Looks selectively at round hole in formboard, Object permanence: removes
lid to find toy.
R: By 10 months, understands “no” and
recognizes own name. By 12 months, follow a
command with gestures
E: By 10 months usually has a vocalization for a
parent, echolalia is common from about 7-30
months.
By 12 months has 1-2 words, immature jargoning

Front 90

18 (motor, social, adaptive, problem-solving, language)

Back 90

GM: climbs on furniture at 15 months. By 18 months, can push/pulls large object, throws ball while standing, seats self in small chair
Proto-declarative point by 15 months (A child points
to an item to point it out to an adult; the goal = adult attention)
Drinks from cup without spilling, imitates household tasks, hugs parents, plays in company of other children, symbolic play directed to
doll,
VS: Matches pairs of objects, circle in formboard reversed, round pegboard,
finish (spont.) spontaneous scribble, imitates
single stroke, tower of 4
R: 3 body parts, Points to self:
E: 10-25 words, giant words, names one picture, mature jargon

Front 91

24 (motor, social, adaptive, problem-solving, language)

Back 91

Jumps in place, kick ball, walks down stairs with rail, throws overhand
S/A: Parallel play, uses spoon
well, removes clothes
without buttons
Sorts objects, matches objects
to pictures, attempts to fold
paper
R: 2-step command,
understands me/you E:
two word phrase N+V,
50+ words, refers to self
by name, pronouns
inappropriately (I, me, you)

Front 92

36 (motor, social, adaptive, problem-solving, language)

Back 92

G: up stairs,alternating feetheel walk
toe walk pedal tricycle
S/A: independent eating, cut with scissors, toilet trained. string small beads
VS/VM: draw circle, build bridge
L: Age
boy/girl
first and last name,
plurals and past tense
correctly,
three word sentences
what sleep in? write with?
hear with?

Front 93

PKU

Back 93

o Characterized as elevated blood phenylalanine = need to restrict dietary sources
o Clinically:
 Causes severe mental retardation if untreated
o Incidence = 1:15,000
 Variety of genetic forms – most common is “classic” PKU = remain on low phenylalanine diet for life
o Cause:
 Defective phenylalanine hydroxylase found only in the liver
 Used to convert phenylalanine to tyrosine and require tetrahydrobiopterin as a cofactor
 1-2% have defect in the synthesis of the cofactor
o Treatment:
 Needs to occurs as phenylalanine is an essential amino acid = cannot be made by body
 Patients placed on low phenylalanine medical food and formulas
 Problem is diet must be maintained for life = difficult and expensive

Front 94

MSUD

Back 94

o Defect in leucine, isoleucine, and valine metabolism
o Results in ketonuria, irritability, and poor feeding by 48 hrs of age
o Life-threatening = causes severe neurological damage
 Lethargy, apnea, opisthotonas by day 5 and then into coma
o Treatment:
 Protein restriction and high calorie Branched chained AA free formula

Front 95

Medium-chain acyl-CoA dehydrogenase deficiency – MCAD

Back 95

Testing is done indirectly by mass spectrometry of accumulated acylcarnitines
o Carnitine is necessary for fatty acid oxidation, therefore by determining the type of fatty acid bound to carnitine in excess can indicate the block in the pathway

MCAD: Results in defects in breakdown – beta oxidation – of fats
o During starvation mode, main energy source is from beta oxidation, especially for liver, heart, and skeletal muscle.
 Therefore with deficiency, patient begins to have symptoms 12hrs post last meal (infants), 24hrs in adults.
o Symptoms include:
 Hypoglycemia, rhabdomyolysis, cardiomyopathy, recurrent Reyes-like attacks
o Treatment:
 Avoiding fasting and supplementation with carnitine
 If there is severe liver or heart damage, then transplant effected organs

Front 96

Sickle cell

Back 96

Major reason for screen = prevent sepsis from encapsulated bacteria as spleen is most likely to be damaged
o Tend to be put on penicillin prophylaxis

Front 97

Biotinidase deficiency

Back 97

o Biotin is an essential vitamin used as a cofactor for enzymes (the carboxylases)
o holocarboxylase synthetase adds biotin to these enzymes
o When enzymes are degrades, lysine remains attached to biotin = called biocytin
o Biotin is liberated via biotinidase to be reused in another enzyme
o Incidence of deficiency in about 1/60,000
o Clinically:
 Ok for first 4 months due to stores of biotin
 Eventually stores are depleted and lost in urine in the form of biocytin
 Carboxylase enzyme reactions now malfunction
 Symptoms:
 Alopecia, seborrhea, seizures, hearing impairment, and developmental delay
 Without diagnosis = infants left neurologically damaged
o Treatment:
 Very effective with biotin supplementation
 “take a pill every day and you’ll be cured”

Front 98

Galactosemia

Back 98

Disorder of catabolism of monosaccharide galactose found a break down product of lactose
o any defect in 3 enzymes (galactokinase, galactose-1-P uridyltransferase (the biggie!) and UDP-galactose-4-epimerase
o G1P Uridyltransferase defect = SEVERE disease
o Clinically:
 Present with liver toxicity in the 1st 2 weeks of life = jaundiced and ill-appearing, elevated transminases, galactose in urine (reducing substance)
 Also see hypoglycemia, hepatitis, and cataracts

 Boards presentation: hepatitis, jaundice, E.coli sepsis
o Treatment:
 Restriction of dietary intake of lactose
 Use lactose-free formula. Symptoms of intoxication rapidly reverse

Front 99

Congenital hypothyroidism

Back 99

o Occurs at a frequency of 1:4K!
o 95% are due to defect in the formation of a thyroid gland (athyreosis)
o End result is insufficient thyroid hormone
o Clinically:
 Results in severe mental retardation and growth deficiency
o Treatment:
 Exogenous thyroid hormone replacement

Front 100

Cystic Fibrosis

Back 100

Autosomal recessive disorder in which there is a mutation in the cystic fibrosis transmembrane conductance regulator (CTFR)
o Clinically:
 Significant thickening of mucous in ductal tissues resulting in major damage to the pancreas, respiratory, and reproductive systems
o Treatment:
 If early = improvement of nutrition and growth
 Genetic counseling of at risk families

Front 101

Congenital deafness

Back 101

o Incidence is estimated to be 1:1000
o Identification = early speech therapy and hearing augmentation devices
o Better long term speech preservation

Front 102

Tanner staging breast

Back 102

Prepubertal; elevation of
papilla only
• Breast bud stage; elevation of
breast and papilla as a small
mound
• Further enlargement of breast
and areola, with no separation
of their contours
• Projection of areola and
papilla to form a secondary
mound above the level of the
breast
• Mature stage; recession of the
areola to the general contour
of the breast

Front 103

tanner staging female pubic hair

Back 103

I: Prepubertal
II: Sparse growth of pubic hair chiefly along the labia
III: Hair spreads sparsely over mons
IV: Adult type hair, smaller distribution
V: Hair is spread to medial thighs

Front 104

Male tanner pubic hair + other male signs

Back 104

I: Prepubertal
II: Sparse growth of pubic hair chiefly along the base of the penis
III: Hair spreads sparsely over midline
IV: Adult type hair, smaller distribution
V: Hair is spread to medial thighs

First sign of puberty in boys is testicular
enlargement
• Most of the increase in testicular size is due to
seminiferous tubular development
• Spermarche (appearance of spermatozoa in
early morning urine occurs at a mean age of 13.4
years (Tanner stage III to IV)

Front 105

Central vs. peripheral precocious puberty (def and examples)

Back 105

Definition:

Central Precocious Puberty
– Premature reactivation of hypothalamic-pituitarygonadal axis
– Increased secretion of GnRH
• Peripheral Precocious Puberty
– Non-GnRH-stimulated gonadotropin secretion
– Secretion of sex steroids independent of hypothalmic
GnRH and pituitary LH, FSH
– Exogenous sex steroid or gonadotropin administration

Gonadotropindependent (central)
– Idiopathic (girls)
– CNS abnormality
(e.g. tumor, other)
– Primary Hypothyroidism
– HCG producing tumor
(boys)

Peripheral
Gonadotropinindependent (peripheral)
– Girls
• Ovarian Cyst
• Ovarian Tumor
• Adrenal Tumor
• McCune-Albright syndrome
– Boys
• Congenital adrenal
hyperplasia
• Testotoxicosis
• Testicular (leydig cell
tumor)Diagnosing Precocious Pube

Front 106

Premature thelarche

Back 106

Usually appears in girls before age 3-4
• Transient (mean duration 2 years)
• Age of onset of puberty is normal
• Vaginal mucosa may be estrogenized, but
no other signs of puberty are noted
• Plasma estradiol is usually normal
• GnRH test is pre-pubertal

Premature thelarche may occur in those girls
who secrete FSH longer than average or
whose breast primordia is more sensitive to
estrogens

Front 107

Premature adrenarche

Back 107

Clinical signs of male androgen production (pubic
hair, body odor, acne) without signs of true
puberty (no penis enlargement, testis or breast
development)
• Plasma DHEA-sulfate is early pubertal
• GnRH test is pre-pubertal
• High incidence of insulin resistance

Front 108

Constitutional delay vs. hypogonadotropic hypogonadism

Back 108

Both have low prepubertal gonadotropins and low serum gonadal steroids.

CD: Patient usually has short stature for chronological
age but appropriate height and growth for bone
age. Adrenarche and gonadarche are delayed. just a late bloomer, runs in the fam. Growth may fall to 5% after birth and stay on that curve. GnRH stimulation test shows prepubertal response. bone age delayed. SPontaneous puberty results

HH: Patient may have anosmia (Kallman) or other
associated pituitary deficiencies. If gonadotropin
deficiency is isolated, patient usually has normal
height and growth rate. Adrenarche may be
normal in spite of absent gonadarche (serum
DHEA sulfate may be pubertal).

Front 109

Hypergonadotropic Hypogonadism

Back 109

Elevated gonadotropins, but low serum gonadal steroids

Patient may have abnormal karyotype and stigma
or Turner or Klinefelter syndrome.

Front 110

LGBT health disparities

Back 110

Cigarette smoking
 2x more likely to smoke than heterosexuals (both lesbians and gay)
 38-59% of LGB youth vs 28-35% of hetero youth
 30K LGB deaths related to tobacco disease
o Alcohol and recreations drug use/abuse
 Increased risk for lesbian and bisexual women
 Alcohol, marijuana, cocaine, and others
 Gay and bisexual men: 35% - greater lifetime rates of cocaine, marijuana, MDMA, meth, and popper use. Alcohol use is similar to heterosexual men
- Lesbians more likely to be overweight
- Gay/bisexual higher lifetime eating disorder prevalence
Both have more cardiovascular risk factor (stress?)
Lesbians have lower screening rates for cervical cancer due to false assumption that they are not at risk, which is false. Still have to do pap for female to male transgender
Lesbians possibly have more risk factors for breast cancer. (just treat them the same as other women) dont forget ftm patients.

Anal cancer - x80 in MSM. Anal pap every 1-3 years. Other stis.

Lesbians have greater risk of STIs (vaginosis) than other women.


Front 111

Teratomas (embryonal germ cell tumor)

Back 111

Mature teratomas – benign – 99% of teratomas
 10-15% bilateral
 MUST represent all 3 germ layers
 Typically occurs during reproductive years
1) Dermoid cyst variant - This is a mature teratoma but contains ONLY tissues derived from skin. Typically unilocular cyst containing sebum and hair. Only has 1% chance of malignant transformation. If it does it transforms into SQUAMOUS CELL CARCINOMA
2) Monodermal or specialized teratomas. RARE, usually benign and unilateral (Struma Ovarii; Teratoma containing mature thyroid tissue which Can be hyperfunctioning)
3) Immature teratomas – semi malignant
- Commonly occurs in children and young adults (avg 18yo)
- Gross: Predominantly solid with Necrosis and hemorrhage
- Micro: ALL 3 germ layers, Variably immature tissue. Histological grade is Based on proportion of immature neuroectodermal cell. Treatment: Chemotherapy and/or surgery

Front 112

Dysgerminoma

Back 112

2% of all ovarian malignancies but 50% of all malignant germ cell neoplasms (Equivalent to testicular seminoma)
Occurs commonly in young adults
- Gross: Solid, Nodular, Rubbery
- Micro: Primitive cells in nets, sheets with Large nuclei Fibrous stroma with/without lymphocytes
- Prognosis: AGGRESSIVE tumor but highly responsive to chemotherapy = >80% 5yr

Front 113

Endodermal sinus tumor - Yolk sac tumor

Back 113

UNCOMMON – 2nd most common malignant germ cell tumor. Occurs in Children or young adults
- Micro: Loose stroma. Schiller-Duval bodies (malignant epithelium around vessel - no fibrovascular core). Hyaline droplets. Alpha-fetoprotein (+)
 Aggressive tumor but responsive to chemotherapy

Front 114

Granulosa-theca cell tumor (and the consequences)

Back 114

o 5% of ovarian tumors
o Usually unilateral
o Occurs more commonly in older women (2/3 post menopausal)
o MOST produce estrogen
o Micro:
 Predominantly Granulosa cells with varying proportion of theca cells
 Small% of malignant cells
 5-25% have multiple recurrences
 Coffee bean looking nuclei!!!
o Clinical consequence:
 Young girls:
 Precocious puberty
 Adult woman:
 Endometrial hyperplasia
 Endometrial carcinoma – 10-15% of cases

Front 115

Thecoma fibroma

Back 115

o 4% of all ovarian tumors
o 90% are unilateral
o Gross:
 Firm, white to yellow (thecoma)

o Micro:
 Fibroblasts with variable number of spindle cells with lipid droplets (theca cells)

o Symptoms:
 Pain and pelvic mass
o Associations:
 Ascites – 40% of cases >6cm mass
 Meigs syndrome = ovarian tumor + ascites + right sided hydrothorax!
 Basal cell nevus syndrome

Front 116

Sertoli-Leydig cell tumor

Back 116

o Produce testosterone
o Causes masculinization or defeminization
o Occurs in 2nd/3rd decade of life
o Unilateral
o Gross:
 Resemble granulosa-theca tumors
o Micro:
 Cells arrange like seminal vesicles without the presence of sperm

Front 117

Congenital cryptorchidism

Back 117

Present in approximately 1% of 1-year-old boys,
cryptorchidism is the incomplete descent or maldescent of the intra-abdominal
testes. Usually an isolated anomaly, cryptorchidism can rarely be found in combination with other abnormalities of the GU tract, such as hypospadias. It is usually unilateral, although 25% of cases are bilateral. Testicular descent is controlled by hormonal factors, such as mullerian-inhibiting substance and
androgens, although the precise cause of cryptorchidism is poorly understood.
The condition leads to arrest of spermatogenesis and progressive parenchymal atrophy. Clinical complications include increased risk of traumatic injury and hernia (due to abnormal location in the inguinal canal), sterility if both testes are
involved, and 5 to 10 fold increased risk of germ cell tumors (the cause for
this association is unknown). The treatment is a surgical procedure which places
the testis into the scrotal sac (orchiopexy), although this procedure does not
guarantee normal fertility.

Front 118

Germ cell tumor (male) facts

Back 118

Over 95% of testicular tumors are of germ cell origin. In general, germ cell tumors affect young
males, with increased incidence in North America and Northern Europe, where they are the most common cancer in men between ages 15 and 44. Approximately 90% of germ cell tumors are associated with isochromosome of short arm of chromosome 12.
These neoplasms are classically divided into seminomatous, including seminoma and
spermatocytic seminoma, and nonseminomatous germ cell tumors (NSGCT), including embryonal carcinoma, yolk sac tumor, choriocarcinoma and teratoma.
This distinction is clinically important for several reasons. NSGCT usually affects
younger males, in the 2nd to 3rd decades, while seminomatous tumors tend to
occur later. Seminomatous tumors generally metastasize through lymphatics,
which NSGCT often spread through hematogenous and lymphatic routes.
Finally, seminomas are exquisitely radiosensitive tumors, while NSGCT are usually treated with chemotherapy following surgery.

Front 119

Seminoma

Back 119

Gross pathology
Diffuse enlargement of the testes due to a grey, cream or pale pink homogenous
lobulated mass. The tumor has a well-defined border. Hemorrhage and cyst
formation is rare. Occasionally, the tumor is composed of multiple identicalappearing nodules.
Microscopic pathology
The tumor is composed of a uniform population of seminoma cells, usually
arranged in sheets or clusters, separated by fibrous bands which contain
lymphocytes. Tumor cells have clear to pale cytoplasm due to high glycogen
content, large centrally placed nuclei with prominent nucleoli and well-defined cell
borders. Seminomas show diffuse immunohistochemical staining for placental
alkaline phosphatase (PLAP) and C-kit (CD117) in 85-100% of cases.
Clinical features
Peak incidence is in the 4
th
decade. Most patients (70%) present with localized
disease (Stage I). When it does metastasize, the tumor goes through lymphatics to lymph nodes. Seminoma has a characteristic sonographic appearance, well-defined and hyperechoic. The tumor has a relatively good prognosis, due to high radiosensitivity.

Front 120

Spermatocytic seminoma

Back 120

Gross pathology
The tumor mass is usually soft, well circumscribed, with a bulging mucoid cut
surface. It may be lobulated, cystic hemorrhagic or focally necrotic.
Microscopic pathology
Non-cohesive tumor cells are present in a scant or edematous stroma. In
contrast to classic seminoma, lymphocytic infiltrates are rare. The tumor is
composed of three different cell types, with marked variability in cell size.
Immunohistochemical markers useful in classic seminoma and other GCT’s are
usually negative.
Clinical features
Most tumors occur in older males, with peak incidence in the 7
th
decade. There
is no ovarian counterpart. Spermatocytic seminoma rarely metastasizes and has
an excellent prognosis.

Front 121

Embryonal carcinoma

Back 121

Gross pathology
The tumor causes slight or moderate testicular enlargement. The neoplasm is
soft and granular, grey, white or pink-tan, often with hemorrhage and/or necrosis.
It bulges from the cut surface, and is not well demarcated from the surrounding
testicular tissue.
Microscopic pathology
The growth pattern is varied, with solid, papillary and cleft-like spaces suggestive
of primitive gland formation. Tumor cells are large, with abundant clear to
basophilic cytoplasm and large, irregular nuclei with prominent nucleoli and
frequent mitotic figures. Cell borders are indistinct. Vascular and lymphatic
space invasion are common. This tumor usually stains for CD30, is negative for
PLAP, and shows only rare, focal cells positive for alpha fetoprotein (AFP) and
human chorionic gonadotrophin (HCG). The lack of differentiation reflects the
relatively primitive nature of this neoplasm.
Clinical features
Embryonal carcinoma first occurs at puberty, with peak incidence at 30 years of
age. This tumor tends to grow faster than seminoma, and patients may present
with testicular pain or from consequences of metastatic spread. Only 2-10% of
tumors are “pure” embryonal carcinoma, which portends a worse prognosis than
mixed germ cell tumor.

Front 122

yolk sac tumor (male)

Back 122

Gross pathology
This tumor is generally non-encapsulated, and presents as a soft, pale gray gelatinous or mucoid mass. Large tumors show hemorrhage and/or necrosis
Microscopic pathology
Characteristic patterns include a reticular or lace-like arrangement of cells, papillary structures, solid cords, or cyst formation. Structures known as SchillerDuval bodies may be present, which are composed of a central capillary lined on the surface by cuboidal tumor cells. Tumor cells are generally small to
medium size, round to cuboidal, and often contain eosinophilic HYALIN GLOBULES within
the cell cytoplasm. (These globules stain for alpha fetoprotein (AFP) and α1-
antitrypsin.) AFP positivity and the presence of Schiller-Duval bodies are keys to diagnosis.
Clinical features
This tumor commonly presents as an asymptomatic scrotal mass in young children, with median age 16-17 months, and has a good prognosis in this age group. 90% of patients have elevated serum AFP levels. Pure yolk sac tumor in adults is rare (mixed).

Front 123

choriocarcinoma male

Back 123

Gross pathology
Choriocarcinoma usually presents as a hemorrhagic nodule, with a surrounding rim of tan or fibrous tissue. In some cases, there is marked regression of the tumor with only a small fibrous scar.
Microscopic pathology
The tumor is a mixture of malignant syncytiotrophoblastic, cytotrophoblastic and intermediate trophoblastic cells. Cells arepleomorphic with abundant eosinophilic cytoplasm, and appear highly malignant. Hemorrhage and necrosis
are common, as is blood vessel invasion. The tumor is positive for HCG
Clinical features
Pure choriocarcinoma is rare (<1% of GCT’s), although choriocarcinoma is a component of mixed GCT in 8% of cases. The median age for diagnosis is
between 25 and 30 years. The tumor is identical to that arising from the female placenta or ovary, and can also arise from sequestered rests of pluripotent cells in the mediastinum and abdomen!! Although the prognosis for uterine choriocarcinoma is good, testicular choriocarcinoma is an aggressive, highly
malignant neoplasm. Patients have high levels of circulating beta HCG, which can be helpful in making the diagnosis. Testicular choriocarcinoma metastasizes early, with lymphatic spread to retroperitoneal lymph nodes and hematogenous
spread to lungs, liver, GI tract, spleen, brain and adrenal glands. Hemorrhage of multiple visceral sites is termed “choriocarcinoma syndrome.” Patients tend to present with advanced stage disease. Because the neoplasm does not respond well to radiation and chemotherapy, the prognosis is poor.

Front 124

leydig cell tumor

Back 124

Gross pathology
These lesions are usually well circumscribed, often encapsulated, and are
usually small (between 3-5 cm). The cut surface is homogenous, yellow to
mahogany brown, sometimes with hyalinization or calcification.
Microscopic pathology
The tumor cells resemble normal Leydig cells, and are medium to large
polygonal cells with abundant eosinophilic cytoplasm and distinct cell borders.
Nuclei are round to oval with prominent nucleoli. Some cytologic atypia may
occur, although mitoses are rare. Intracytoplasmic eosinophilic crystals (Reinke
crystals) may be present. Leydig cell tumors stain diffusely for vimentin, inhibin
and various steroid hormones.
Clinical features
Leydig tumors are seen in children between 3 and 9 years, but are most common in adults between the 3rd and 6th decades. Painless testicular enlargement is the most common presenting symptom. As the tumor can elaborate significant amounts of sex steroids, including androgens and estrogens, gynecomastia may occur and children may present with precocious puberty. Approximately 10% of Leydig cell tumors may have malignant features.

Front 125

sertoli cell tumor

Back 125

Gross pathology
These tumors are tan yellow to gray white, lobulated, well circumscribed masses. Focal hemorrhage may be present, but necrosis is generally not seen.
Microscopic pathology
The tumor cells resemble normal Sertoli cells, with oval, round or elongated nuclei and pale cytoplasm. Cells are usually bland and uniform, with rare
mitoses. The tumor cells tend to be arranged in characteristic trabeculae, often forming tubules surrounded by a basement membrane. Similar to Leydig cell tumors, Sertoli cell tumors are positive for vimentin, and demonstrate variable positivity for inhibin (40%).
Clinical features
occur in adults (median age 45 years). Most are benign, although 10% demonstrate
malignant behavior. These neoplasms also elaborate sex steroids, but in
insufficient amounts to cause clinical effects.

Front 126

gonadoblastoma

Back 126

This is a rare neoplasm comprised of both stromal and germ cell components.
Gonadoblastoma is almost always associated with aberrations of sex
chromosomes, most commonly mixed gonadal dysgenesis (commonly 45, X /
46, XY mosaicism). The estimated risk of developing gonadoblastoma in this
setting is 15-25%. In half of patients with gonadoblastoma, the germ cell
component will undergo malignant transformation to seminoma.

Front 127

testicular lymphoma

Back 127

Gross pathology
Lymphoma usually involves the testes as a homogeneous tan fleshy mass, often
with poor distinction from surrounding testicular tissue.
Microscopic pathology
The tumor cells generally replace the testicular architecture in a diffuse pattern.
Testicular lymphomas are almost always diffuse large B cell lymphomas, with
histologic appearance similar to that seen in lymph nodes and other sites. The
malignant cells are dyshesive, with moderate amounts of pale eosinophilic
cytoplasm, enlarged nuclei and vesicular to coarse nuclear chromatin. By
immunohistochemistry, the tumor is diffusely positive for leukocyte common
antigen (CD45) and B cell markers CD20 and CD19.
Clinical features
Lymphoma represents 5% of testicular tumors, and is the most common
neoplasm of the testes in men over age 60. Testicular lymphoma may be the
primary manifestation of malignant lymphoma (primary testicular lymphoma), or it
may occur during the clinical course of a patient with established lymphoma
(secondary involvement of testis). 80-90% of primary testicular lymphoma is of
the diffuse large B-cell type. Patients with primary testicular lymphoma are
treated aggressively with chemotherapy and irradiation, although most
demonstrate widespread dissemination within 2 years. Although prognosis
depends somewhat on the histologic type of lymphoma and stage of disease,
prognosis is generally poor

Front 128

Hydrocele, hematocele, other celes

Back 128

Hydrocele is a pathologic collection of serous fluid around the testicle, secreted by the tunica vaginalis. Hydrocele is relatively common and
may occur in older children, adolescents and adults due to trauma, hernia,orchitis or testicular neoplasm. Hydrocele in newborns (10-20 per 1000 live
births) is due to abnormal patency of the process vaginalis, in which the space surrounding the testis communicates with the peritoneal cavity. If the lumen of the patent process vaginalis is large enough, the hydrocele may be accompanied by hernia (protrusion of intestine into the scrotal sac). Transillumination (shining a strong light through the enlarged scrotum) is a simple test that can distinguish between a translucent hydrocele and a solid testicular mass. Treatment of hydrocele includes surgical drainage of fluid with resection of the redundant sac tissue, with repair of the process vaginalis in newborns.

Additional pathologic fluid collections surrounding the testis include spermatocele, hamatocele and chylocele. Spermatocele is a collection of serous fluid and sperm, which may develop from dilation of the epididymal tubule. Hematocele is a collection of blood, usually due to trauma, torsion or bleeding diathesis. Chylocele is the accumulation of lymph in the setting of lymphatic obstruction. Varicocele and vasitis nodosa are diseases of the spermatic cord. Varicocele arises from varicose dilatation of the veins of the spermatic cord. Vasitis nodosa is a benign reactive condition of the vas deferens, usually occurring after vasectomy, associated with the formation of suture granulomas or sperm granulomas.

Front 129

Arch 1 (CN, M, B, A, P)

Back 129

CN - 5
M - masseter
B - malleus, incus, mandible
A - maxillary
P - auditory tube

Front 130

Arch 2 (CN, M, B, A, P)

Back 130

CN - 7
M - stapedius, stylohyoid
B - stapes, styloid process, lesser hyoid
A - stapedius, hyoid artery
P - palatine tonsils

Front 131

Arch 3 (CN, M, B, A, P)

Back 131

CN - 9
M - stylopharyngeal
B - greater hyoid
A - common and interal carotid
P - parathyroid, thymus

Front 132

Arch 4 (CN, M, B, A, P)

Back 132

CN - 10 - superior laryngeal
M - pharynx, larynx
B - laryngeal cartilages
A - R. subclavian and arch of the aorta
P - parathyoid, c cells

Front 133

Arch 6 (CN, M, B, A, P)

Back 133

CN - 10, recurrent laryngeal
M - none
B - none
A - pulmonary, ductus arteriosis
P - none

Front 134

histo of genital duct (tubuli recti, rete testeis, epididymis, dd, sv, ej)

Back 134

seminiferous tubules - basal compt and adlumnial compt. the outer wall of sem tubule is composed of three to five layers of modified contractile fibroblasts called myoid cells.
tubuli recti - simple columnar or cuboidal epithelium
rete testis - simple cuboidal epithelium w/ a single cilium and a few short microvilli (the ciliated cells move the tubule fluid and nonmotile spermatozoa towards epididymis)
Epididymis - pseudostratified columnar epithelium, smooth muscle (inc from 1 to 3 layers distally). Principal cells have a long microvilli called stereocilia on lumnial surface (secretory and absorptive activity) + basal cells (prob stem cells). BONUS - sperm spend 2 weeks here in order to later develop motility (thats when they encounter seminal vesicle ercretions)
DD - internal mucosa of pseudostratified columnar with stereocilia, thick muscularis, external adventitia.
Seminal vesicle - highly folded mucosa (honeycomb) of psuedostratified cuboidal to columnar epithelium with short rounded basal cells. Muscularis and adventitia. Makes fructose, fibrinogen
Ejaculatory duct - no muscular bc it is in the fibromuscular stroma of prostate

Front 135

Physiologic targets of estrogen

Back 135

Cardio - heart, vascular endothelium
Nervous system - hippocampus, medial preoptic aea, hypothalamus
GI - esophagus, salivary glands, intestinal epithelial cells
Misc - bronchial smooth muscle, osteoblasts, peiodontal ligament, renal cortex and medulla, liver, pancreatic beta cell
Reflect differences in pre and post menopausal women in heart disease, osteoporosis, colon cancer, neurodegenerative disease, allergy and autoimmune disease

Front 136

Examples of age-dependent vs. age-associated disease

Back 136

Dependent - invariably gonna happen
- cataracts
- hearing loss
- osteoporosis
-osteoarthritis
- nodular prostatic hyperplasia
- senile hyperinflation of lungs

Assoc.
- systemic atherosclerosis
- temporal arteritis
- myeldodysplastic syndrome
- htn
- dm 2
- vulnerability to infections
- alzheimer disaes
- many cancers
- glaucoma

Front 137

Individual, organ, cellular changes with aging

Back 137

Individual - theme is loss of function, diminished ability to respond to stress. Examples: decreased BMR, std cell water, GFR, max breathing capacity, conduction velocity. Fat goes up, muscle goes down
Organs - atrophy
Cell: decreased oxidative phosphorylation, dec DNA, RNA synth, dec capacity to take up nutrients. Accumulation of age-related products: lipofuscion (lipid oxidation), amyloid deposits in the heart, AGE products (for ex, leading to decreased skin elasticity, senile catacts, diabetes changes)

Front 138

Human progeroid syndromes (name, gene, lifespan, features)

Back 138

1) Hutchinson-gilford, Nuclear Lamin A/C, abt 25 years. Features: skin atrophy, loss of subq fat, hair loss, arteriosclerosis, bone loss
2) Werner, WRN (helicase), abt 60 yrs. Features: skin atrophy, CATARACTS, MILD DM, OSTEOPOROSIS, ALOPECIA, atherosclerosis, cancer predispistion, HYPOGONADISM
3) Cockayne, Type A, CKN1 (WD repeat protein), abt 40 yrs. Features: NEURODEGENERATION, CATARACTS, skin photosensitivity, hypogonadism
4) Cockayne Type B, ERCC6 (helicase)
5) Ataxia telangiectasia, ATM (kinase which senses dna damage), abt 45 years. Features: CEREBELLAR DYSfunction, sensitivity to ionizing radiation, cancer predisposition, hypogonadism

Front 139

Effect of bedrest on MSK, CVS, Pulm, Skin system

Back 139

1) MSK falls, fractures, weakness, dependency
• ~1% Loss of strength per day
• Muscle atrophy
• Further reductions in aerobic capacity
• Impaired joint range of motion
• Development of contractures
• Accelerated bone loss
2) CVS - dehydration, orthostasis/falls, delirium
Further reductions in plasma volume
• Further diminished baroreceptor sensitivity
• Enhanced venous compliance (lower extremities)
• Increased resting heart rate
3) PULM - penumonia, MI, delirium
• Further reductions in ribcage expansion
• Impaired ventilation
• Enhanced V/Q mismatch
• Further reduction in p02 by ~8mmHg
• Further impaired cough
4) Skin - pressure sores, sepsis, pain, immobility
- Exposure to
prolonged pressure,
shear, friction and
moisture
5) Renal/hormonal reg of water/electrolyte balance
• High risk for
dehydration
• High risk for hyponatremia
• Prescribing errors due to dosing by serum Creatinine, and not by estimating CrCl as a measure of GFR

Front 140

Physiology of elders that predispose them to problems from bedrest

Back 140

MSK:
• Reduced muscle mass and strength
• Impaired aerobic capacity
• Diminished cartilage strength
• Diminished tendon flexibility
• Reduced bone density
CVS:
• Impaired thirst
• Impaired baroreceptor sensitivity
• Decreased plasma volume
• Decreased total body water
• Impaired LV compliance
• Decreased maximum
heart rate.
• Reduced cardiac output with exercise
Pulm
• Reduced ribcage expansion
• Diminished lung elasticity and recoil
• Reduced alveolar surface area
• Reduce hypoxic drive
• Drop in PaO2
• Reduced function and number of cilia
• Impaired cough
• Increased A-a gradient
- Reduced forced vital capacity
Skin:
• Thinner epidermis and dermis
• Reduced vascular supply
• Reduced subcutaneous fat
• Reduced cellular turnover
• Reduced moisture content
Renal/Hormonal:
• Loss of glomerular and tubular mass
• Creatinine production falls at nearly the same rate as the renal clearance of creatinine, and a normal serum creatinine often represents a decline in kidney function
• Increased ANH (atrial natriuretic hormone) secretion
• Reduced aldosterone levels
• Normal to elevated
basal ADH (antidiuretic hormone) secretion, and decreased renal responsiveness to ADH
• Predisposition to volume depletion and free water excess*

Front 141

Cellular aging

Back 141

• Cell-autonomous defects: delayed or blunted reaction to stimulation
(reduced signaling, transcription, etc.); proliferative decline, altered
function, cellular re-programming
• Population changes: decline in new cell production, reduced removal of
cells by apoptosis, expansion of some cell clones at the expense of others,
defects in homeostasis
• Changes in the microenvironment – stromal aging, extracellular matrix
alterations, accumulation of inflammatory mediators, dysregulated
cytokines , etc.

Front 142

Trisomy 18 vs. 13

Back 142

18 -
1) Small, mentally retarded, failure to thrive
2) short sternum, small pelvis, rocker bottom feet
3) cardiac, renal, intestinal defects
4) Death in less than a year

13-
1) microcephaly and abnormal brain developement (like holoprosencephaly)
2) cleft lip and palate, polydactyly
3) cardiac dextroposition, septal defect