Exam 1-Reproductive Flashcards
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1
Q
What weeks does the migration of the urogenital germ cells occur?
A
week 4 they appear in the yolk sac
weeks 5/6 the arise in the urogenital ridge which becomes the epithelium and stroma of the ovary
2
Q
How do the mullerian ducts form the uterus and vagina?
A
at week 6 the ducts descend into the pelvis where they caudal ends fuse to form the uterus and upper vagina while the cephalad stay separate and become the fallopian tubes
3
Q
What does the urogenital sinus form in the adult?
A
lower vagina and vestibule
4
Q
What happens to the mesonephric ducts?
A
they usually degenerate in females but remnants can be left behind to become Gartner duct cysts in the cervix and vagina
5
Q
What are some of the common infectious agents and their causes in the GU tract of females?
A
candida, trichomonas and gardnerella can cause pain but are not serious, N. gonorrhoeae and chlamydia can cause infertility, while U. urealyticum and M/ hominis can casue preterm delivery, HSV can cause painful ulcerations and HPV can cause cancers
6
Q
Who gets HSV and where?
A
affects lower genital tract in females most commonly the cervix, vagina and vulva, two serotypes- HSV1 is oral, HSV2 is genital, but they can switch, 30% of females have HSV2 Ag by 40yo, but men will also get HSV
7
Q
What is the manifestation of HSV?
A
1/3 of new cases are symptomatic with lesions after 3-7 days as well as fever, malaise, tender inguinal lymph nodes, red papules move to vesicles then ulcers, the inner ulcers have purulent discharge and pelvic pain, those around the urethra cause pain with urination, they spontaneously heal after 1-3 weeks but are highly transmittable
8
Q
What causes HSV flare-ups?
A
it leis dormant in ganglia and any decrease in immune function can cause it to reappear
9
Q
What morphology is seen in HSV infections?
A
typically already ulcerated, with desquamated epithelium, multiple viral inclusions causing ground glass appearance
10
Q
What are the risks involved in transmission of HSV?
A
women are more likely to get HSV, condoms can help prevent transmission, HSV1 exposure reduces chances of getting HSV2, it can be transmitted to the newborn child, worse if active during birth and primary infection of mother so C-section is warranted, HSV2 infection however makes HSV1 acquisition and trasnmission more likely
11
Q
How is HSV infection diagnosed in the lab and then treated?
A
PCR and culture, serum Ab is indicative of recurrent/latent infection, treat with acyclovir to reduce length of symptoms, no vaccine exists
12
Q
What are the characteristics of molluscum contagiosum?
A
poxvirus causing skin or mucosal lesions, 4 types, MCV-1 is most prevalent while MCV-2 is most often sexually transmitted, between 2-12yo, can affect trunk, arms and legs as well as genitals if sexually transmitted, morphology shows pearly white dome-shaped papules with dimpled center, contain cytoplasmic inclusions
13
Q
What fungal infections affect the lower genital tract?
A
candida is most common but yeast all a normal part of vaginal flora and symptoms occur as result of ecosystem imbalance, DM, ABx, pregnancy and immune disorders can cause this imbalance, presents with vulvovaginal pruritis and curdlike discharge, severe infections can cause ulcers, Dx with PAP or KOH prep, not an STI
14
Q
What are the charactersitics of trichomonas vaginalis
A
large, flagellated ovoid protozoan
(fungi), STI, 4 days to 4 weeks for development, asymptomatic or frothy yellow discharge, discomfort, dysuria, dyspareunia, vaginal and cervical mucosa is fiery, red with dilated vessels “strawberry cervix”
15
Q
What is characteristic of gardnerella vaginalis?
A
gram neg, bacillus, main cause of bacterial vaginosis, thin, green-gray, malodorous(fishy) discharge, PAP reveals squamous cells with shaggy coating coccobacilli, can cause premature labor
16
Q
What 2 entities can caue vaginitis and cervicitis?
A
ureaplsma urealyticum and myoplasma hominis spp. also caues of chorioamionitis and preamture delivery
17
Q
What are characteristics of chlamydia trachomatis?
A
can cause cervicitis, but also ascends into uterus and fallopian tubes to cause endometritis and salpingitis or PID
18
Q
What is PID and what can cause PID?
A
infection that begins in the lower genital tract and spreads upward to include most of the female genital system, causing pelvic pain, adnexal tenderness, fever and discharge, N. gonorrhoeae and chlamydia can cause PID, infections after birth(puerperal infections) can also lead to PID, these usually include multiple bacteria, they produce worse and deeper infections because they start in the uterus
19
Q
What morphology is seen in PID?
A
gonoccocal infections are characterized by marked acute inflammation of mucosal surfaces, cause acute supurative saplingitis, growing towards the ovarycausing salpingo-oophoritis causing tubo-ovairan or pylosalpinx abscesses, scaring can occur known as chronic salpingitis, if secretions build up this is known as hydro salpinx
20
Q
What clinical findings are seen in PID?
A
acute complications are peritonitis and bacteremia leading to endocarditis, meningitis and suppurative arthritis, chronically, PID may lead to infertility, tubal obstruction, ectopic pregnancy, pelvic pain and adhesions leading to intestinal obstruction
21
Q
What Tx is helpful in PID?
A
ABx or surgical removal if the abscess is walled off, post-abortion or postpartum are more difficult to control
22
Q
What is a Bartholin cyst?
A
inflammation and abscess of the Bartholin gland, commonly occur at all ages, lined by transitional or squamous epithlium, 3-5cm in diameter, produce pain and can be cut out or simply opened
23
Q
What is leukoplakia and how does it affect the vulva?
A
opaque, white plaquelike thickening that may be prurutic and scaly, can be caused by benign, premalignant or malignant disorders
24
Q
What are some causes of vulvar leukoplakia?
A
inflammatory dermatoses, lichen sclerosis and squamous cell hyperplasia, neoplasias (VIN), Paget disease and invasive carcinoma
25
What are characteristics of lichen sclerosis?
smooth white plaques or macules that at anytime can grow together creating a porcelain surface, vulva can become atrophic with vaginal orifice constriction, morphologically there is thinning of the epithelium, basal cell degeneration, hyperkeratosis, superficial slcerosis and lymphocytic invasion, common in post menopasual women, autoimmune nature and noneoplastic but present with some carcinomas
26
What occurs during squamous cell hyperplasia?
aka, hyperplastic dystrophy or lichen simplex chronicus, caused by friction on skin from scratching, leukoplakia, acanthosis, and hyperkeratosis, mitotic activity without atypia, nonneoplastic but present with some carcinoma
27
What benign exophytic lesions can present on the vulva?
fibroepithelial polyps or skin tags
| squamous papillomas, non keratinized covering
28
What are characteristics of condyloma acuminatum?
benign genital warts caused by low risk oncogenic HPV 6 and 11, multiple, cover the perineal and perianal regions but can be seen on the cervix, tree like core covered by thick squamous epithelium with koilocytic atypia, which is nuclear enlargment, hyperchromasia and nuclear halo, not precancerous
29
Who gets vulvar squamous neoplastic lesions and what are the major types?
women over 60, infrequent, commonly SCC, basaloid/warty carcinomas(30%) and keratinizing SCC(70%)
30
What are the characteristics of basaloid/warty carcinomas?
develop from classic VIN, which is seen in women of reproductive age and is CIS or Bowen disease, risk factors include multiple partners, young age of intercourse, MSM, due to relation to HPV, highest rick in F over 45yo or the immunosupressed, peak incidence is sixth decade
31
What are the characteristics of KSCC?
typically after longstanding lichen sclerosis or squamous cell hyperplasia, peak incidence in eighth decade, develops from differentiated VIN or VIN simplex, TP53 mutations have been seen, not HPV related
32
What is the morphology of classic VIN?
white hyperkeratotic or raised lesions, epidermal thickening, nuclear atypia, increased mitoses, basaloid carcinoma show nests/cords of tightly packed cells similar to basal layer of epithelium, with necrosis, warty carcinoma is exophytic, papillary and shows koilocytic atypia
33
What morphology is seen in differentiated VIN?
marked basal atypia, nest and tongues of malignant tissue with keratin pearls
34
What is special about papillay hidradenoma and Paget disease?
can occur in vulva and breasts
35
What are the characteristics of papillary hidradenoma?
sharply circumscribed nodules on the labia, can cause ulcerations, identical to intraductal papllioma of the breast, papillary projections with two layers, upper columnar and deeper flattened myoepithelial cells, similar to sweat glands
36
What are characteristics of extramammary Paget disease?
similar to the disease of the breast, presents with pruritic, red, crusted, maplike are on the labia, not associated with cancer unlike that in the breast, can be excised but due to lateral spread clean margins are difficult to obtain
37
What is the morphology of Paget disease?
intraepithelial proliferation of malignant cells, paget cells are larger than keratinocytes and are found in clusters, PAS, Alcian blue or mucicarmine staisn, express cytokeratin 7
38
What is thought to cause septated vagina?
DES or other unknown factors casuign the Mullerian ducts not to fuse correctly
39
What is vaginal adenosis?
patches or islands of glandular epithelium that does not regress in the vagina
40
What are Gartner duct cysts?
remnants of the Wolffian ducts(mesonephros) filled with fluid
41
What causes cervicitis?
disturbance in bacterial flora or pH near the cervix, suppression of lactobacilli, infections from gonococci, chlamydia, myoplasmas and HSV
42
What are characteristics of endocervical polyps?
benign growths, sessile to polypoid, loose fibromyxomatous stroma covered by glands, can cause spotting, excision is curative
43
Where does cervical cancer rank amongst the worlds women and what is the major cause?
3rd overall, HPVs(16 & 18)
44
Where can HPV cause cancer?
SCC of the cervix, vagina, penis, vulva, anus, tonsil and other oropharyngeal sites
45
How long do HPV infections take to clear?
50% cleared in 8 months, 90% cleared in 2 years
46
What cell type does HPV infect?
immature basal cells cannot infect mature cells
47
How HPV able to cause cancer?
E7 inhibiting Rb and E6 binding TP53
48
What is the classification system for cervical precursor lesions?
Mild dysplasia-CIN I (LSIL)
Moderate dysplasia-CIN II (HSIL)
Sever dysplasia-CIN III (HSIL)
Carcinoma in situ-CIN IV (HSIL)
49
How is squamous intreapeithelial lesion diagnosed?
nuclear atypia, with enlargement, hyperchromasia, coarse chromatin granules and variation in nuclear siz and shape, contain koilocytic atypia
50
What percentage of ISL progress to cancer?
LSIL typically regress and cannot progress to carcinoma, while HSIL are at high risk for carcinoma, 80% of LSIL and 100% HSIL are associated with high-risk HPVs
51
Who is likely to get cervical carcinoma?
45yo is average, commonly SCC, followed by adenocarcinoma which develops of adenocarcinoma in situ, caused by HPVs
52
What morphology is seen in cervical carcinoma?
SCC shows tongues and nests of malignant squamous epithelium, keratinized or not, which invade unerlying stroma, adenocarcinoma shows proliferation of glands with malignant endocervical cells, dark nuclei, and decreased cytoplasm, neuroendocrine is similar to small cell carcinoma of the lung
53
How does cervical carcinoma tend to spread?
contiguous spread to tissue
54
What is seen clinically with cervical carcinoma?
more than half in women who had not been screened, can be treated by cervical excision, total hysty is best, small-cell cancer has worst prognosis, most patients with advanced cervical carcinoma die of local tumor invasion
55
How can cervical cancer be screened for and prevented?
PAP smear at 21 and every 3 years after, if abnormal, culposcopy is performed, biopsy if needed, boys and girls(11 up to 26) can get HPV vaccines for types 6, 11, 16, 18
56
What does the endometrium of the uterus look like in its menses and proliferative phases?
menses- functional layer shed
proliferative- rapid growth of glands and stroma due to estrogen, glands are straight, lined by tall pseduostratified columnar cells, numerous mitotic figures, no secretion or vacuolation, stroma has spindle cells with scant cytoplasm
57
What does the endometrium of the uterus look like at ovulation and post ovulation?
ovulation-proliferation stops, and progesterone causes differentiation
postovulation- appearance of secretory vacuoles in the glands, secretory activity is highest now(3rd week) and vacuoles move to the surface, week 4 tortuous glands which are exhausted and shrinking giving a sawtooth appearance
58
What does the uterine endometrium look like during the late secretory phase?
stroma changes due to progesterone, spiral arterioles appear with increased ground substance and edema, hypertrophy occurs next(predicidual change) and a resurgence of mitoses occur, lymphocytes and nuetrophils are also around but normal, corpus luteum degrades and bleeding occurs with the next menses
59
What is the most frequent cause of dysfunctional bleeding?
anovulation
60
What can cause anovulation?
endocrine disorders, ovarian lesions, and generalized metabolic disturbances
61
What occurs during anovulation?
excessive endometrial stimulation by estrogens unopposed by progesterone, repear occurences spur biopsies, which show stromal condesation and eosinophilic epithelial metaplasia, lacks progesterone related histo, endo is comprised of mitotic figures and pseudostratified glands
62
What happens during an indadequate luteal phase?
infertility, with increased bleeding or amenorrhea, caused by inadequate progesterone during post-ovulatory phase, biopsy shows lagging histology from earlier periods
63
What occurs during acute endometritis?
uncommon, limited to bacterial infection(strep, staph, chlamydia) after delivery or miscarriage due to retained products of conception, nonspecific stromal inflammation, removal of the products and ABx typically clear the infection
64
What are characteristics of chronic endometritis?
caused by PID, retained gestational tissue, IUD, TB(miliary or TB salpingitis), Dx is based on plasma cells in stroma, complaints of bleeding, pain, discharge and infertility are common, chlamydia is associated with acute and chronic forms, ABx to prevent sequelae
65
What causes most vaginal carcinomas?
high risk HPVs, SCC arising from vaginal intraepithelial neoplasia, typically at the upper posterior wall
66
Where do vaginal carcinomas metastasize?
lower 2/3 go to inguinal lymph nodes, upper 1/3 spread to iliac nodes
67
What are characteristics of embryonal rhabdomyosarcoma?
sarcoma botryoides, uncommon, found in infants and children under 5yo, polypoidal growth, small cells with oval nuclei with protruding cytoplasm, resemble tennis rackets, cause death by penetrating the peritoneum or obstructing the urinary tract, surgery and chemo to treat
68
What are the characteristics of endometriosis?
women in 4rd and 4th deacades, presence of ectopic endometrial tissue outside of the uterus, may include glands and stroma or only stroma, most frequently occurs in the ovaries, uterine ligaments, rectovaginal septum, cul de sac, peritoneum, bowel/appendix, cervix/vainga/tubes, lap scars, leads to infertility, dysmenorrhea, and pelvic pain,
69
What are the 2 categories of endometriosis' origin?
cells from the uterus migrating or cells outside uterus that can give rise to endometrium
70
What are the 4 theories of endometriosis?
regurgitation theory-retrograde menstruation through fallopian tubes into the peritoneum
benign metastates-uterine endometrium spreads to distant sites
metaplastic theory- endomterial tissue arises from coelomic epithelium from which the mullerian ducts arise and can produce ectopic tissue
extrauterine stem/progenitor cell theory- BM stem cells can differentiate into endometrial tissue
71
Which theory explains the anatomical location but not many other problems in endometriosis?
regurgitation theory, doesn't explain the amenorrheic women, or men with endometriosis after estrogen therapy fro prostate cancer,and distant sites like the brain and lungs, the rate of endometriosis does not match the occurrences of retrograde menstruation
72
what factors play a role in the pathogenesis of endometriosis?
release of proinflammatory factors(PGE2, TNF-a, IL-1b,IL-6. VEGF, MCP-1), increased estrogen production by endometrial cells due to high levels of aromatase(not in normal tissue) also depends on PGE2, increased estrogen responsiveness but decreased with progesterone
73
What is the relation between endometriosis and ovarian cancer?
3x increase in women with endometriosis, PTEN and ARID1A mutations in cysts
74
What morphology is seen in endometriotic lesion bleeds?
response to extrinsic cyclic hormones and intrinsic signals, red-brown appearance just beneath the surface, hemorrhage can lead to fibrous adhesions. ovaries are markedly cystic filled with fluid from bleeds(chocolate cysts or endometriomas), surrounding tissue shows "powder burn" marks caused by hemosiderin
75
What is the morphology of atypical enometriosis?
likely precursor to ovarian cancer, cytologic atypia of epithelial lining, glandular crowing due to proliferation, looks like hyperplasia
76
What is the clinical presentation of endometriosis?
sever dysmenorrha, dysapreunia, pelvic pain due to bleeding and uterine adhesions, pain with defecation and dysuria, infertility is common in 30-40%
77
What is adenomyosis?
endometrial tissue within the myometrium in continuity with the endometrium, same symptomatology as endometriosis, can occur with endometriosis
78
What are the characteristics of endometrial polyps?
sessile projections into the cavity, asymptomatic or cause bleeding if ulcerated of necrotic, contain chromosomal rearrangements similar to the benign tumors, the glands may be hypertophic or atrophied but can be functional, may be responsive to estrogen but not progesterone, can be caused by tamoxifen to treat breast cancer, atrophic polyps are typically found in post-menopausal women due to lack of estrogen on old polyps
79
What is endometrial hyperplasia?
cause of abnormal bleeding and precursor to the most common type of endometrial cancer, increased gland to stroma ratio, shares genetic mutations with carcinoma, occurs from prolonged estrogenic stimulation of endometrium(anovulation, endogenous estrogen, exogenous estrogen), two types:non-atypical and atypical
80
What conditions are associated with endometrial hyperplasia?
obesity, menopause, PCOS, granulosa cell tumors, excessive ovarian cortical function, prolonged estrogen therapy, similar to some endometrial carcinomas in the future
81
What mutation is common to endometrial hyperplasia and endometrial carcinoma?
PTEN, negative regulator of (PI3K)/AKT, this becomes overactive, found in 1/5 of hyperplasias and 30-80% of
cause carcinomas, loss pf PTEN can cause hyperresponisveness to estrogen
82
What is Cowden syndrome?
germline mutation in PTEN, with high incidence of endometrial carcinoma and breast cancer
83
What morphology is seen in atypical endometrial hyperplasia?
increased gland to stroma ratio, some stroma is retained, rarely progress to adenocarcinoma, will atrophy with withdrawal of estrogen
84
What morphology is seen with atypical hyperplasia?
compact glands with atypical nuclei, back to back glands, round cells without perpendicular orientation, open vesicular chromatin in the nuclei, overlap with histo of endometrioid adenocarcinoma, 23-48% have carcinoma on hysty
85
How is atypical endometrial hyperplasia managed?
hysty or progestin therapy and cloe f/u for those wanting to become pregnant but after birth the hysty is performed
86
What are characteristics of endometrial carcinoma?
most common invasive cancer of female genital tract, two broad categories, type I and II
87
What is seen with type 1 endometrial carcinoma?
55-65yo, unopposed estrogen, obesity, infertility, HTN, DM, endometrioid morphology, hyperplasia precursor lesion, mutated genes include: PTEN, ARID1A, PIK3CA, KRAS, FGF2, MSI, CTNNB1, TP53, it follows an indolent course and uses lymphatogenous spread
88
What is seen with type 2 endometrial carcinoma?
65-75yo, atrophy of endometrium and thin physique, serous, clear cell mixed mullerian morphology, serous EIT carcinoma is the precursor, genetic mutations: TP53, PIK3CA, FBXW7, CHD4, PPP2R1A, aggressive course with intraperitoneal and lymphatogenous spread
89
What is a hallmark of type 1 endometrioid carcinoma?
PI3K/AKT pathway mutation
90
What cancerous syndrome is associated with type 1 endometrial carcinoma?
HNPCC, hereditary nonpolyposis colorectal carcinoma, these DNA repair gene mutations are seen in 20% of sporadic endometrial cancers
91
What morphology is seen in type 1 endometrioid cancer?
localized polypoid tumor or tumor that diffusely infiltrates the endometrial lining, spreads via direct invasion, can create palpable mass on broad ligament, metastasizes to lymph nodes and then lungs, bone and liver, well(mostly normal tissue), moderately(less normal with 50% or less solid tumor) and poorly differentiated(over 50% solid) tumors
92
What is the staging for type 1 and 2 enometrial carcinomas and MMMTs?
stage 1 - confined to corpus uteri
stage 2- confined to uterine body and cervix
stage 3- extends outside the uterus but no out of the true pelvis
stage 4- extends outside true pelvis and involves mucosa of bladder or rectum
93
What are characteristics of type 2 endometrial carcinoma?
10 years older than type 1, with endometrial atrophy, poorly differentiated or grade 3, serous is most common, overlaps with ovarian serous carcinoma, other types such as clear cell and MMMTs are type 2, TP53 mutation in 90%
94
What is the morphology of type 2 endometrial carcinomas?
small atrophic uteri, large bulky tumors, serous EIC is precursor, papillary growth pattern with cytologic atypia, high nuclear to cytoplasmic ratio, atypical mitotic figures, hyperchromasia, prominent nucloeli, can be mostly glandular, different from type 1 from cytologic atypia, serous carcinoma can be associated with extensive peritoneal disease, spread by indirect routes
95
What is the clinical presentation of endometrial carcinoma?
over 40yo, typically 55-65, no screening test, typically causes irregular(post-menopausal) bleeding with excessive leukorrhea, dx by biopsy, prognosis depends on staging and grading at Dx, good survival for stage I (grade 1/2) but drops for stage 1 grade 3 and even more for stage 2 or 3, AA women are more prone to serous carcinoma, tx with PI3K/AKT inhibitors or chemo/radiation
96
What are the characteristics of malignant mixed mullerian tumors?
carcinosarcomas, endometrial carcinomas with malignant mesenchymal component, epithelial and stomal components are based on the same founding cell, mutations tend to be PTEN, TP53, and PIK3CA, found in postmenopasual women with bleeding
97
What morphology is seen in MMMTs?
bulky polypoid can protrude through the cervical os, usually adenocarcinoma(endometrioid, clear cell or serous) mixed with malignant mesenchyme(sarcoma) elements, can mimic extrauterine tissue(muscle, bone, fat),
98
What are the characterstics of endometrial adenosarcomas?
large broad based endometrial polypoid growths, may prolapse through cervical os, malignant stroma with benign but abnormally shaped glands, 4th and 5th decades, low-grade malignancy, difficult to distinguish from large benign polyps, adenosarcoma is estrogen sensitive and responds to oophrectomy
99
What are charactersitics of endometrial stromal tumors?
benign nodules or stromal sarcomas(low/high grade), low-grade caused by JAZF1 combined with SUZ12, which silences genes and upregulates oncogenic genes, high grade contain different translocations causing fusion genes, almost half recur, 50% 5 yr survival for low and worse for high
100
What are characteristics of uterine leiomyomas?
uterine fibroids are the most common tumor in women, smooth muscle benign neoplasms, HMGIC, HMGIY gene mutations, as well as MED12 in 70%
101
What morphology is seen in uterine fibroids?
sharply circumscribed, round, firm, grey-white tumors from small to pelvis filling, found in myometrium but rarely uterine ligaments, lower uterine segment or cervix, can be intramural, submucosal or subserosal, have whorled pattern of smooth muscle on section, muscle cells are uniform, with oval nuclei and long bipolar cytoplasmic processes, benign variants can have nuclear atypia and giant cells
102
What are the rare variants of leiomyomas?
bening metastasizing leiomyoma, extends into vessels and spreads to other sites(lung), also disseminated peritoneal leiomyomatosis, presents as multiple small peritoneal nodules, both are benign
103
What are the clinical findings in leiomyomas?
asymptomatic, even when large or numerous, signs include abnormal bleeding, urinary frequency, sudden pain from infarction, impaired fertility, they increase frequency of spontaneous abortion, fetal melpresentation, uterine interia and potpartum hemorrhage, malignant transformation is rare
104
What are the characteristics of leiomyosarcomas?
uncommon, from myometrium or endometrial stromal precursors, rather than leiomyomas, frequent deletions in DNA, also contain MED12 like the leiomyoma, MED12 is unique to smooth muscle tumors
105
What morphology is seen in leiomoysarcomas?
two patterns: bulky, fleshy masses that invade uterine walls or polypoid masses that project into the cavity, wide range from well differentiated to highly anaplastic, distinction form leiomyoma is nuclear atypia, mitotic index and zonal necrosis, 10 mitoses per 10hpf is malignant, or 5 mitoses per 10hpf and large cells or nuclear aytpia is also malignant
106
What are the clinical findings in leiomyosarcoma?
before or after menopause, peak at 40-60yo, often recur with surgery and over half metastasize, overall survival at 5 years is 40% but only 15% if anaplastic
107
What is involved in inflammation of the fallopian tubes?
supurative salpingitis is caused by any pyogenic organism, gonococcus is causative in 60% of cases with chlamydia being responsible for the others, these are related to PID, TB salpingitis is rare in the US but common in endmeic TB regions, causes infertility
108
What benign tumors and cysts are related to the fallopian tubes?
paratubal cysts are tiny and translucent, larger varieties found on the fimbriae or the broad ligament are called hydatids of Morgagni, arise in the remnants of mullerian duct and are lined with benign serous epithelium, adenomatoid(mesothelioma) tumors can occur similar to the testes
109
What cancer can arise in the fallopian tubes?
adenocarcinoma, rare though, cause abnormal bleeding, discharge or abnormal PAP smear most are stage 1 but 40% of patients are dead in 5 years, chemo treatment, can be ovarian cancer cause
110
What are the most common tumors in the ovaries and what cells can they come from?
benign cysts and tumors, mullerian epithelium, germ cells, and sex-cord stromal cells
111
What are cystic follicles?
very common in the ovary, originated from unruptured graffian follicles or that have ruptured but immediately sealed
112
What are the morphological features of cystic follicles?
usually multiple, clear serous fluid, gray, glistening membrane, Dx by palpation or US, can be painful, have granulosa lining cells if pressure isnt too high and thecal cells on the outside are pale(luteinization), or if very pronounced(hyperthecosis) which is assocaited with increased estrogen production
113
What are luteal cysts?
corpora lutea, present in normal ovaries of reproductive age, lined by yellow tissue containing luteinized granulosa cells, can rupture causing peritoneal reaction, can resemble endometrial cysts with old hemorrhage and firbrosis
114
What is polycystic ovarian syndrome?
PCOS, complex endocrine disorder with hyperandrogenism, mesntrual abnormalities, polycystic ovaries, chronic anovulation and decreased fertility, also called Stein Levanthal syndrome
115
What are characteristics of PCOS?
associated with T2D, obesity(insulin resistance), premature atherosclerosis, marked by androgen enzyme dysfunction, numerous cystic follicles that enlarge the ovaries but not specific for PCOS, elevated estrone is as well as increased risk for endometrial hyperplasia and carcinoma
116
What is ovarian stromal hyperthecosis?
ovarian stromal disorder seen in postmenopausal women which overlaps PCOS, uniform enlargement of the ovary, with white-tan appearance, usually bilateral and shows hypercellular stroma and luteinization of cells which are visible in nests with vacuolated cytoplasm, virilization is more profound than PCOS
117
What is theca lutein hyperplasia of pregnancy?
physiologic condition mimicking PCOS and stromal hyperthecosis in response to pregnancy hormones, theca cells proliferate and perifollicular zone expands, as follicles regress the concentric theca-lutein hyperplasia may appear nodular, not to be confused with true luteomas of pregnancy
118
What are the characteristics of ovarian tumors?
80% are benign, between ages 20-45, borderline tumors occur at older ages, malignant tumors are more common between 45-65yo, most ovarian tumors have spread outside the ovary at Dx therefore they cause a disproportionate amount of deaths
119
What are the classifications of ovarian tumors?
surface/fallopian tube epithelium and endometriosis: serous, mucinous, endometrioid, clear cell, transitional, epithelial-stromal
stromal cell tumors: granulosa, fibromas, fibrothecomas, thecomas, sertoli-leydig cell, steroid cell
germ cell: teratoma, gysgerminoma, yolk sac, mixed germ cell
120
Where do most ovarian tumors arise from?
mullerian epithelium, three types: serous, mucinous and endometrioid
121
How are benign ovarian tumors classified?
cystadenoma, cystadenofribroma or adenofibroma depending on major component, glands, fibrous or both, but if benign are cystadenocarcinomas
122
What are the two categories of ovarian carcinomas?
type I low grade or type II high grade from STIC
123
What are the characteristics of serous tumors?
cystic but also tubal-like epithelium, risk factors for benign version unknown, but for malignant type they are nulliparity, FHx, heritable mutations, 70% benign, 30% malignant, lower between 40-59yo with use of OC or tubal ligation, high grade tumors can arise from fallopian tubes based on BRCA1/2 germline mutation study(serous tubal intraepithalial carcinoma, STIC), BRCA women will have salpingoophrectomy instead of only oophrectomy
124
What genetic mutation is associated with ovarian carcinoma?
BRCA1 and BRCA2, 20-60% by age 70
125
What genetic mutations are assocaited with low and high-grade ovarian carcniomas?
low-KRAS, BRAF or ERBB2
high-TP53 and other oncogenes, BRCA is rare
126
What morphology is seen in serous ovarian carcinoma?
multicystic, papillary epitheliumd within fibrous walled cysts, or mass projecting from ovary, benign tumors are smooth and become more papillae-like as they become more invasive, bilaterality is common as is surface location
127
What morphology is seen in serous borderline tumors of the ovary?
increased complexity of stromal papillae, mild nuclear atypia but without invasion, referred to as micropapillary carcinoma, precursor to low grade serous carcinoma
128
What morphology is seen in high-grade serous carcinoma of the ovary?
more complex growth patterns and widespread infiltration or effacement of underlying stroma, marked nuclear atypia, pleomorphism, atypical mitotic figures, and multinucleation, serous tubal carcinoma is similar without invasion, psammoma bodies are seen but not specific, can spread to omentum and peritoneum(if unencapsulated) and are associated with ascites
129
What is the clinical scenario with serous ovarian carcinomas?
if confined to the ovary,borderline is 100% 5 yr survival, 70% for malignant, if involving peritoneum its 90% and 25% respectively
130
What are characteristics of mucinous ovarian tumors?
20-25% of all ovarian neoplasms, middle adult life rarely before puberty or after menopause, , majority are borderline or benign, KRAS mutation is consitent in these tumors
131
What morphology is seen in mucinous ovarian tumors?
rarely involve the surface unlike serous and only 5% are bilateral, much larger tumors up to 25kg, multiloculated with sticky, gelatinous fluid, under the microscope they all tall columnar cells with apical mucin and no cilia(gastric or instestinal-like)
132
What morphology is seen in mucinous ovarian carcinomas?
confluent glandular growth(expansile invasion), similar to intraepithelial carcinoma for this, good prognosis unless spread beyond the ovary
133
What can be seen clinically with mucinous ovarian tumors?
pseudomyxoma peritonei = extensive mucinous ascites, cystic implants on peritoneal surfaces, adhesions, and ovarian involvement(most commonly caused by the appendix), can lead to intestinal obstruction and death
134
What are characteristics of endometrioid ovarian carcinomas?
only 10-15% of all ovarian cancers, benign versions are called endometrioid adenofribromas, different from serous and mucinous due to glands recembling benign or malignant endometrium, carcinomas can arise in the setting of endometriosis(15-20%)
135
What genetic mutations are seen in endometrioid ovarian carcinomas?
PI3K/AKT(PTEN, KRAS) and DNA mismatch repair genes and CTNNB1
136
What morphology is seen in endometrioid ovarian carcinomas?
solid and cystic, 40% are bilateral which usually means extension beyond the GU tract, look endometrial in origin
137
What are characteristics of clear cell carcinoma of the ovary?
benign or malignant they are rare, large epithelial cells with clear cytoplasm and resemble hypersecretory gestational endometrium, considered variants of endometiroid carcinoma due to occurrence with endmetriosis, they also share similar PI3K/AKT pathway mutations, solid(sheets) or cystic(spaces), 90% at 5yrs if confined to ovary
138
What characteristics are found in cystadenofibromas of the ovary?
pronounced proliferation of fibrous stroma under the epithelium, multiloculated with papillary processes, may contain, mucinous, serous, endometrioid and transitional (Brenner tumor) epithelium
139
What are characteristics of transitional cell tumors of the ovary?
Brenner tumor, resemble urothelium and are typically benign, present due to size and if malignant are in stage 1 or low-grade
140
What morphology is seen in Brenner tumors?
solid or cystic, unilateral, sharply demarcated nests of transitional epithelium within normal ovarian stroma, mixed in malignant cells are called malignant Brenner tumors while over 50% malignant cells are called transitional cell carcinoma of the ovary
141
What are the similar presentations of all ovarian carcinomas?
lower abdominal pain and enlargement, GI distress, urinary frequency, dysuria, pelvic pressure, malignant cause weakness, weight loss and cachexia occasional ascites if extending through the capsule containg tumor cells, regional lymph nodes are involved, half of malignant cases have metastases across midline
142
What is the treatment for ovarian tumors?
benign can be resected, malignant are more challenging but chemo, radiation and surgery
143
How is ovarian cancer detected and prevented? Why is it important?
assays, Ag screens or products of tumors, CA-125 can be used to monitor after treatment, BRCA+ can have prophylactic salpingo-oophrectomy, most women are diagnosed with ovarian cancer at high stage disease
144
What are the main germ cell tumors?
teratoma, yolk sac, choriocarcinoma and dysgerminoma
145
What are the 3 teratoma types?
mature(benign), immature(malignant) and monodermal(specialized)
146
What are characteristics of mature teratomas?
cystic, dermoid cysts, lined by skin-like structures, found in young women during the active reproductive years, can present with paraneoplastic syndromes(inflammatory limbic encephalitis)
147
What morphology is seen in mature teratomas?
bilateral 10-15%, unilocular cysts with hair and sebaceous material, thin wall lined with gray-white wrinkled epidermis with hair shafts, teeth and calcification as well, 1% can undergo malignant transformation to SSC or others, can be solid without cysts
148
What are the characteristics of monodermal/specialized teratomas?
struma ovarii and carcinoid, unilateral, mature thyroid tissue only in struma ovarii, which can cause hyperthyroidism, carcinoid comes from intestinal tissue and may be functional and can cause carcinoid syndrome(via 5-hydroxytryptamine(tryptophan)), if metastatic intestinal carcinoid it is bilateral, the two can combine to form strumal carcinoid teratomas
149
What are charateristics of immature teratomas?
resemble embryonal and immature fetal tissue, unlike benign, found in prepubertal adolescents and woung women around 18, grow quickly, penetrate the capsule and spread, stage 1 has excellent prognosis, high grade in the ovary can be treated with chemo, no recurrence is excellent prognosis
150
What is the morphology of an immature teratoma?
bulky with smooth outside and solid, similar inside to mature teratoma, teeth, bone, hair, sebaceous material, also necrosis and hemorrhage, also immature tissues of above this is the basis of grade for malignancy
151
What are ovarian dysgerminomas related to in males?
testicular seminoma
152
What are the characteristics of dysgerminomas?
occur in 2nd and 3rd decades, rarely in childhood, can occur with gonadal dysgenesis(psuedohermaphroditism), non-functional, can produce hCG which confirma syncytiotrophoblast giant cells, express OCT3/4 and NANOG which maintain pluripotency, express KIT and 1.3 have activation of KIT(diagnostic marker/target for therapy), MALIGNANT, 1/3 are aggressive, 80% overall survival
153
What morphology is seen with dysgerminomas?
unilateral tumors from tiny to entire abdomen size, solid yellow-pink-white, soft, large vesicular cells with clear cytoplasm, well defined boundaries and normal nuclei, lymphocytic infiltrate, can be in a cystic teratoma or may contain a teratoma
154
What are the characteristics of yolk sac tumors?
endodermal sinus tumor, 2nd most common germ cell malignancy, extraembryonic differentiation of malignant germ cells, alpha-fetoprotein elaboration, glomerulus like structure with central vessel enveloped by tumor cells with a space outside also lined by tumor cells(Schiller-Duval bodies), hyaline droplets in all tumors, some stain for AFP, typically children or young women with rapidly growing pelvic masses in a single ovary
155
What are the characteristics of ovarian choriocarcinomas?
placental origin, extraembryonic differentiation of malignant germ cells, can only be confirmed in prepubertal females because after it could be ectopic ovarian pregnancy origin, most exist in combo with other germ cell tumors, similar to placental variation, aggressive and metastasize to lungs, bone and liver by time of Dx, elaborate hCG, not responsive to chemo, usually fatal
156
What is ovarian embryonal carcinoma?
highly malignant tumor of primitive embryonal elements similar to that of tests
157
What is a polyembryoma?
malignant tumor containing embryoid bodies
158
What is a mixed germ cell tumor?
contain variations of the germ cell tumors, yolk sac, choriocarcinoma, dysgerminoma, teratoma
159
What are the sex cord-stromal tumors of the ovary?
granulosa cell, fibroma, thecoma, and fibrothecoma, sertoli-leydig cell
160
What are the characteristics of granulosa cell tumors?
95% adult and some juvenile, types based on age and morphology, 2/3 in postmenopausal women, malignant potential
161
What morphology is seen in granulosa cell tumors?
unilateral, size varies, solid, cystic, lipids in the active version, polygonal cells growing in sheets, can have small acidophilic glandlike structures(Call-Exner bodies), can have thecoma component or luteinization
162
What is seen clinically in granulosa cell tumors?
elaborate large amounts of estrogen(rarely androgens) and behave like low-grade malignancies, precocious puberty in the young, assocaited with proliferative breast disease, endometrial hyperplasia and carcinoma, inhibin is elevated, FOXL2 has been reported in these tumors(mostly adult type)
163
What are characteristics of fibromas, thecomas and fibrothecomas?
fibroblasts(fibromas), plumpspidnle cells(thecoma) or a mixture, thecomas are active and fibromas are not, fibromas are unilateral mostly, solid, glistening, white-yellow with fibroblasts and collagen, found as pelvic masses sometimes painful with ascites(if hydrothorax then Meigs syndrome), also with basal cell nevus syndrome, usually benign, if mitotic activity is found with increased nuclear to cyto ratio then fibrosarcoma is Dx
164
What are the characteristics of Sertoli-Leydig cell tumors?
functional and cause masculinization or defeminization, similar to that of the testes, women in 2nd/3rd decade, DICER mutation which processes miRNA, block normal female development with atrophy of breasts, amenorrhea, sterility, and hair loss, syndrome can progress to striking virilization with male distribution, clitoromegaly and voice changes,
165
What morphology is seen in Sertoli-Leydig cell tumors?
unilateral, grossly resemble granulosa cell tumors, tubules composed of Sertoli or Leydig cells within stroma in well-differentiated tumors, intermediate diffrentation shows outlines of immature tubules and large eosinophilic leydig cells, poorly differentiated shows disordered disposition of epithelial cord cells
166
What is seen in ovaian Hilus cell tumors?
pure Leydig cell tumor, polygonal cells arranged around hilar vessels, unilateral tumor with large lipid laden Leydig cells with distinct borders and Reinke crystalloids, women present with masculinization with voice changes, and clitoral enlargement(mild compare to S-L tumors), produce testosterone
167
What is seen in pregnancy luteomas?
resembles corpus luteum of pregnancy, virilization in pregnant women and their female infants,
168
What is seen in gonadoblastomas?
germ cells and sex-cord stroma resembling immature sertoli and granulosa cells, occurs in individuals with abnormal sexual development, 80% are phenotypic females, 20% are phenotypic males with female internal organs, cosexistent dysgerminomaexists in 50% of cases
169
What tumors typically metastasize to the ovaries?
mullerian origin: uterus, fallopian tubes, contralateral ovary or pelvic peritoneum, as well as breast carcinoma and GI tract
170
What is a Krukenberg tumor?
metastasis to bilateral ovaries from GI tract, mucin producing signet ring cancer cells, usually gastric
171
What can diseases of pregnancy and the placenta cause?
intrauterine or perinatal death, congenital malformation, intrauterine growth retardation, maternal death and morbidity for mother and infant
172
What is the definition of spontaneous abortion?
miscarriage, pregnancy loss before 20 weeks gestation
173
What are characteristics and causes of spontaneous abortion?
most occur before 12 weeks, caused by fetal chromosome anomalies, maternal endocrine factors, physical defects of the uterus, systemic disorders affecting the maternal vasculature, infections(TORCH)
174
What are characteristics of ectopic pregnancy?
MEDICAL EMERGENCY, implantation of fetus in site other than the uterus, 90% in fallopian tubes, most important risk factor is PID resulting in scarring(chronic salpingitis), also adhesions increase risk along with IUD(doubles the risk),
175
What is the most common cause of hemosalpinx?
tubal pregnancy, should be considered with tubal hematoma
176
What morphology is seen in tubal pregnancy?
embryonal sac surrounded by chorionic villi implants in lumen of tube, villi invade the wall as they would the uterus, over time the wall thins and can rupture causing massive intraperitoneal hemorrhage which can be fatal,
177
What clinical features are seen with ectopic pregnancy?
medical emergency, moderate to sever abdominal pain and vaginal bleeding 6-8 weeks after LMP, hemorrhagic shock and acute abdomen can occur with tubal rupture,Dx base on hCG levels, pelvic US, and biopsy
178
What can cause disorders of late pregnancy?
blood flow interruption, ascending infection, retro placental hemorrhage(abruptio placentae),
179
What are characteristics of twin placenta?
fertilization of two ova or division of one, 3 types: diamnionic dichorionic, diamnionic monochorionic, monoamnionic monochorionic
180
What is a complication of monochorionic twin pregnancy?
twin-twin transfusion, if there is a shunt between the twins arterial and venous supplies of the twins, one will get more blood flow than the other and the lack will underperfuse one while the increase will volume overload the other, both are at risk of death
181
What are different types of placental implantation abnormalities?
placenta previa is implantation in the lower uterine segment or cervix with serious 3rd trimester bleeding, complete will cover the cervical os and requires C section, placenta accreta is partial or complete absence of the decidua and the villi attach to myometrium, can cause sever, life-threatening postpartum bleeds(risks are Hx of placentra previa or C section)
182
What are placental infections and what can they cause?
develop 2 ways: ascending through birth canal(most common) or hematogenously(transplacental), can cause premature rupture of membranes and preterm delivery, amniotic fluid can be cloudy with purulent exudate, and neutrophilic on histo, causes a vasculitis, or acute villitiss if the placenta is infected, common causes are TORCH(toxoplasmaosis, others{syphilis, TB, listeriosis}, rubella, CMV, herpes)
183
What are preeclampsia and eclampsia?
preeclampsia is a systemic syndrome of widespread maternal endothelial dysfunction that presents during pregnancy with HTN, edema, and proteinuria, occurs often in primiparas(first pregnancy), leads to hypercoagulability, ARF, and pulmonary edema, sever eclampsia can lead to hemolytic anemia, elevated lvier enzymes and low platelets(HELLP syndome), distinguished from HTN of pregnancy by proteinuria
184
How does abnormal placental vasculature lead to preeclampsia?
trophoblastic implantation and failure of maternal vessel remodeling, spiral arteries need to be dilated to increase blood flow to the placenta but this fails in preeclampsia leading to fetal ischemia
185
How does endothelial dysfunction play a role in preeclampsia?
in response to hypoxia the placenta relases factors into the maternal circulation that cause an imbalance in aniogenic and anti-angiogenic factors, this leads to endothelial dysfunction, VEGF and TGF-B(NO inducer) are inhibited in these women,
186
What happens to coagulation in preeclampsia?
hypercoaguable state, leading to thombi in arterioles and capillaries especially in the brain, kidney and pituitary, hypercoaguable state is linked to PGI2 reduction due to endothelial dysfunction and increased procoagulant factors, PGI2 is stimulated by VEGF
187
What morphology is seen in preeclampsia?
placental infarcts and exaggerated ischemic changes leading to syncytial knots, retroplacental hematomas, abnormal decidual vessles, liver lesions are seen in subcapsular hematomas, kidney lesions are varaible, dense deposits on the endothelium of BM, mesagnial hyperplasia, fibrin abundance in glomeruli, brain can have microscopic hemorrhages similar to the heart and pituitary
188
What is seen clincally with preeclampsia?
most common after 34 weeks gestation but earlier with hydatidiform mole, kidney disease, HTN or coagulopathy, insidious onset with HTN and edema with proteinuria in several days, HA and vision changes are indicative of severe changes, delivery is Tx of choice, and is necessary if HELLP, fetal demise or maternal organ dysfunction are occurring, HTN and proteinuria ersolve after 2 weeks postpartum
189
What is seen in eclampsia?
CNS involvment with convulsions and eventual coma
190
What are the gestation trophoblastic diseases?
hydatidiform mole, invasive mole, choriocarcinoma,a nd PSTT
191
What are characteristics of hydatidiform moles?
increased risk of invasive mole or choriocarcinoma, cystic swelling of chrionic villi, with variable trophoblastic proliferation, Dx in early pregnancy(9wks) risk is highest eaerly in reproductive years and late
192
What is seen with a complete mole?
fertilization of an egg without maternal chromosomes, 100% paternal DNA, duplication of one spem leads to 46XX homozygous genotype(90%-androgenesis), 10% have heterozygous 46 XX/XY genotype due to 2 sperm fertilizing an empty egg, 2.5% risk of choriocarcinoma
193
What is seen in a partial mole?
69,XXX, etc. due to fertilization of an egg with 2 sperm(sometimes 92XXXY, etc., not associated with choriocarcinoma,
194
What morphology is seen in hydatidiform moles?
delicate, friable, mass with translucent, thin walled, grapelike structures with edematous(hydropic) villi, complete moles involve all the villous tissue, chorionic villi are enlarged, scalloped with central cavitation, covered by trophoblast proliferation, partial moles only have a fraction of villous tissue involved with less trophoblastic hyperplasia
195
What is seen clinically in hydatidiform moles?
usually present with spontaneous miscarriage, complete moles lead to greatly elevated hCG compared to gestation age, rises incredibly fast, after removal hCG is monitored and if continuous elevation then invasive mole is considered(15%)
196
What are characteristics of invasive moles?
mole the penetrates or perforates the uterine wall, myometrium invaded by hydropic villi with cyto and syncytiotrophoblast proliferation, locally destructive invading vessels and parametrial tissue, villi can embolize to lungs & brain but do not grow as metastases, manifests as vaginal bleeding and uterine enlargement, persistently high hCG, responds well to chemo, but can rupture uterus and require hysty
197
What are the characteristics of choriocarcinoma?
malignant neoplasm of trophoblastic cells from normal or abnormal pregnancy, rapidly invasive and metastasizes widely, but responds well to chemo, 50% arise in complete moles, 25% in abortions and the rest follow normal pregnancy,
198
What morphology is seen with choriocarcinoma?
soft, fleshy, yellow tumor with necrosis and hemorrhage, no villi present, entirely syncytiotrophoblasts and cytotrophoblasts, abundant mitoses, invades myometrium, penetrates vessels and extends into uterine serosa and adjacent structures
199
What are the clinical findings in choriocarcinoma?
irregular vaginal spotting of bloody, brown fluid, tumor can appear months after inciting event, hemotogenous spread and can by in vagina(30-40%) and lung(50%) upon Dx, hCH is elevated above those found in moles, but can be so necrotic no hormone is produced, removal and chemo is best Tx w/ nearly 100% remission, can have normal pregnancy after, this is not true of extrauterine choriocarcinomas
200
What is placental site trophoblastic tumor(PSTT)?
neoplastic trophoblasts(intermediate trophoblasts), uterine mass with abnormal uterine bleeding or amenorrhea and moderately elevated hCG, can follow spontaneous abortion, normal pregnancy or hydatidiform mole
201
What are the main components of the breast tissue?
ducts, lobules, interlobular and intralobular stroma, ducts are lined by keratinixinf epithelium at the opening but become a double layer of epithelium with underyling myoepithelium
202
What are the products of lactation?
colostrum is made first(high in protein) which is followed by milk(higher in fat and calories) after progesterone levels begin to drop
203
What are milk line remnants?
line extending from axilla to perineum, nipples or breasts can occur along this line as epidermal thickenings, typically appear as premenstrual enlargements
204
What is accessory axillary breast tissue?
ductal system can extend into the subcutaneous tissue of the axillary fossa or chest wall(tail of spence), this may reduce the effectiveness of prophylactic mastectomy
205
What is a congenital nipple inversion?
failure of nipple to evert during development, common and unilateral, if congenital this is fine, if acquired it may indicate invasive cancer or inflammatory disease
206
What are the most common symptoms reported by women with breast disorders?
pain, palpable mass, nipple discharge
207
Why is pain important in breast disorders?
cyclic with menses(premesntrual edema) or not, if not it could be ruptured cysts, trauma, or infection, most painful masses are benign although 10% are malignant
208
Why are palpable masses important in breast disorders?
must be differentiated from nodularity, most common masses are fibroanedomas, cysts, and invasive carcinomas, benign are more common in premenopausal women, most malignancies occur over 50yo,
209
What does nipple discharge mean in breast disorders?
not common but most worrisome for carcinoma when spontaneous and unilateral, can signal a pituitary issue or thyroid gland problem, or with OCP and other drugs,, blood can occur with pregnancy and benign masses as well as cancer, risk of cancer with discharge increases with age
210
What can a mammogram detect?
small, nonpalpabe, asymptomatic breast cancers and is the most common means to do so, these are seen via densities and calcifications
211
What do densities and calcifications mean on mammogram?
rounded are generally benign while irregular masses are invasive carcinomas, calcifications form on secretions, necrotic debris or hyalinized stroma, usually associated with benign lesions, if malignancy i present the calcifications are small, multiple, clustered, and irreguar
212
What are important inflammatory disorders of the breast?
acute mastitis, squamous metaplasia of the lactiferous ducts, duct ectasia, fat necrosis, lymphocytic mastopathy, granulomatous mastitis
213
What is acute mastitis?
acute bacterial infection typically brought on shortly after breastfeeding begins, S. aureus is most common but also strep, erythematous, painful breast and fever, staph will cause abscess whiel strep causes cellulitis, Tx with ABx and milk expression
214
What is squamous metaplasia of lactiferous ducts?
aka recurrent subaerolar abscess, periductal mastitis, Zuska disease, disease of smokers causing Vitamin A deficiency, women have erythematous subareolar mass that resembles abscess, if recurrent a fistula can be formed opening to the outside of the areola, key feature is keratinizing squamous metaplasia of nipple ducts, keratin plugs the duct leading to dilation or rupture, removal of the duct and fistula can be curative and/or ABx
215
What occurs in duct ectasia of the breast?
palpable periareolar mass with thick white nipple secretions, usually no pain or erythema, usually in 5th or 6th decade, not associated with smokers, dilated ducts are filled with lipid laden macrophages, when ruptured there is a reaction of lymphocytes, macrophages an plasma cells, mimics invasive carcinoma on radiography and clinically
216
How does fat necrosis occur?
protean appearance, can mimic cancer, painless plalpable mass, skin thickening or retraction, densities or calcifications on mamography, related to surgery or trauma to breast, can contain hemorrhage or areas of central liquefactive fat necrosis, surrounded by fibroblasts and chronic inflammatory cells over next few days, giant cells, calcifications and hemosiderin appear then all is replaced by scar tisue
217
What is lymphocytic mastopathy?
sclerosing lymphocytic lobulitis or diabetic mastopathy,
single/multiple hard palpable masses, FNA difficult due to density, atrophic ducts and lobules with thickened BM and lymphocytic infiltrates, common in T1D or autoimmune thyroiditis, autoimmune basis,
218
What is granulomatous mastitis?
manifestation of systemic granulamtous diseases(sarcoidosis, TB, Wegners) localized to breast tissue, granulomatous lobular mastitis only occurs in parous women and is uncommon, may be caused by hypersensitivity reaction during lactation, similar histology is seen in cystic neutrophilic granulomatous mastitis caused by corynebacteria, localized infection is rare and typically in immunocompromised and breast prostheses/piercings
219
What are the benign epithelial lesions of the breast?
nonproliferative breast changes(fibrosytic), proliferative w/ and w/o atypia
220
What are charcateristics of nonproliferative breast changes?
also fibrocystic changes, lump bumpy on palpation, dense breast with cysts or benign findings, no increased risk of breast CA
221
What morphological changes are seen with fibrocystic changes?
CYSTS are dilations of lobules which may combine to form larger cysts, brown-blue fluid, lined with flattened atrophic epithelium of metaplastic apocrine cells, granular eosinophilic cytoplasm like sweat glands, calcifications are common on mammogram, cysts are concerning if solid and firm, dx by resolution after FNA, after rupture the inflammation leads to FIBROSIS, lobules have increased acini called adenosis, and is abnormal in nonpregnant women, the acini are lined by columnar cells which may show flat epitheialatypia due to 16q chromosomal loss, prescursor to low-grade cancer but no increase in risk
222
What are lactational adenomas?
palpable masses in pregnant or lactating women, normal breast with lactation changes, nonneoplastic and are a response to hormones
223
What are the different types of proliferative breast disease without atypia?
epithelial hyperplasia, sclerosing adenosis, complex sclerosing lesion, papilloma
224
What are chracteristics of proliferative breast disease without atypia?
epithelial proliferation without atypia, small increase in cancer risk, incidental findings as densities with calcification on mammography
225
What morphology is seen with epithelial hyperplasia of the breast?
double layer of myoepithelial cells and luminal cells, increased numbers of both, ducts can be distended with lumens at the periphery
226
What does sclerosing adenosis of the breast look like morphologically?
increased number of acini that are compressed and resemble solid cords or double layers of epithelium within dense stroma, sometimes mimics carcinoma, can be palpable, and have radiologic densities and calcifications
227
What is the morphology of complex sclerosing lesions of the breast?
components of sclerosing adenosis, papillomsand epithelia hyperplasia, the raidal sclerosing lesion(radial scar) can mimic carcinoma grossly and histologically, central trapped nidus of endtrapped glands in a hylanizied stroma with long projections, not a scar as in surgey or trauma
228
What does morphology does a breast papilloma show?
grow within ducts with branching fibrovascular cores, seen with epithelial hyperplasia and apocrine metaplasia, can be solitary in the lactiferous ducts if larger, smaller are deeper in the breast, 80% produce discharge, can be bloody if infarction occurs, smaller papillomas become palpable masses or densities/calcifications
229
What are the characteristics of gynecomastia?
enlargement of male breasts, only benign lesion seen in male breast commonly, button-like subareolar mass, uni/bilateral, increased dense collagen connective tissue with epithelial hyperplasia and tapering micropapillae, imbalance between estrogrens and androgens, common around puberty, or with hyperestrinism, importantly also with cirrhosis of the liver due to its estrogen metabolism and older males due to decreased androgens, drugs can cause gynecomastia, Kilnefelter patients are prone, small risk for cancer
230
What are the proliferative breast diseases with atypia and charactersitics?
clonal hyperplasia with some but not all features of carcinoma in situ, atypical ductal hyperplasia and atypical lobular hyperplasia, chromosome 17p gain or 16q loss, similar to CIS, ALH has E-cadherin loss, pagetoid spread due to relation to Paget disease
231
What morphology is seen in atypical hyperplasia of ducts and lobules?
ADH, recognized by resemblance to DCIS, monomorphic proliferation of regularly spaced cells, different from DCIS in that it only partially fills ducts
ALH, identical to LCIS, but cells do not fill more than 50% of the acini in a lobule, atypical cells may lie between BM and overlying normal cells
232
What is the significance of benign epithelial changes?
related to later development of invasive CA, nonproliferative diseases do not have this risk, proliferative has increase of 1.5-2x, while atypia increases this to 4-5x,
233
How does breast carcinoma rank amongst cancers in women?
most common non-skin cancer malignancy, second to lung cancer in deaths
234
What are the 3 groups of breast carcinoma based on gene expression?
ER+, HER2-(50-65%)
HER2+ (10-20%)
ER-, HER2- (10-20%)
235
What is the percentages of tumors based on age?
ER+ increase with age based on use of mammograms and MHT, while ER- HER2- stay constant, ER- HER2+ constitute 50% of tumors in young women
236
What carcinoma has been increase due to mammograms?
DCIS because it cannot be palpated due to lack of mass formation
237
What are the major risk factors for carcinoma of the breast?
germline mutations, first-degree relative with breast cancer, race/ethnicity, age, age at menarche(younger bad), age at first live birth(older bad), benign breast disease, estrogen exposure(MHT), breast density(high is worse), radiation exposure, carcinoma of contralateral breast or endometrium, diet, obesity, exercise, breastfeeding(good), environmental toxins
238
What percentage of familial cancers are related to BRCA1/2?
80-90%, 3% of all breast cancers
239
What are the major tumor suppressors that can be lost in breast cancers?
CHEK2, BRCA1/2, TP53(Li-Fraumeni syndrome), PTEN(Cowden syndrome), STK11(Peutz-Jeghers), ATM(ataxia telengiectasia)
240
What are the major risk factors for sporadic breast cancer?
related to hormone exposure: age at menarche and menopause, gender, breastfeeding, reproductive history, and exogenous estrogens
241
What occurs after a mutation in BRCA1?
1q gain, 16q loss then flat atypia, then atypical ductal hyperplasia followed by DCIS and luminal cancer(ER+,HER2-)
242
What happens with a TP53 mutation?
HER2 amplification, then atypical apocrine adenosis followed by DCIS and HER2 enriched cancer(HER2+)
243
What happens with a BRCA1 mutation?
unsure first step, TP53 mutations followed by BRCA1 inactivation, then DCIS followed by triple negative basal-like carcinoma(ERR-, HER2+)
244
How does neoplastic epithelial cells and stroma interact?
stroma creates an environment conducive to tumorogenesis and growth
245
What type of cancer makes up 95% of all breast malignancies and what percentage are invasive at diagnosis?
adenocarcinomas and 70% have breached the BM at the time of detection
246
What is DCIS?
malignant clonal proliferation of epithelial cells limited to ducts and lobules by the BM
247
What are characteristics of DCIS?
myoepithelial cells are preserved but may be diminished in number, can spread through ductal system, usually detected with mammography, typically identified as calcifications associated with secretory material or necrosis, less common is a palpable mass due to periductal fibrosis
248
What are the 2 major architectural types of DCIS?
comedo and non-comedo
249
What morphology is seen in comedo DCIS?
clustered or linear branching on mammography, two features: pleomorphic high-grade nuclei and central necrosis
250
What morphology is seen in noncomedo DCIS?
lacks high grade nuclei or central necrosis, cribriform DCIS have rounded spaces(cookie cutter) within ducts or a solid DCIS pattern, micropapillary DCIS produces bulbous protrusions without a fibrovascular core arranged in complex intraductal patterns, calcifications can be seen with focal necrosis or intraluminal secretions
251
What is Paget disease of the nipple?
form of DCIS, rare breast cancer manifestation, unilateral erythematous eruption with scale crust, pruritis, DCIS extends into the ductal system without breaking the BM, palpable mass in 50-60%, these women have poorly differentiated ER- HER2+ carcinomas, while women without mass only have DCIS
252
What is LCIS of the breast?
clonal proliferation of cells within ducts and lobules that grow in a discohesive fashion due to acqured loss in E-cadherin(CDH1), called this due to lack of disturbance of lobule architecture,
253
How is LCIS diagnosed?
usually incidental on biopsy due to lack of densities or calcifications
254
What are characteristics of LCIS?
bilateral more often than DCIS, identical cells to atypical lobular hyperplasia and invasive lobular carcinoma,
255
What morphology is seen in LCIS?
uniform population with oval or round nuclei, and small nuclei involving ducts and lobules, mucin + signet ring cells are present, cannot for cribriform or pappila as in DCIS, pagetoid spread is common but does not involved nipple skin, no necrosis or secretory activity, no calcification, always ER+ PR+ but never have HER2 expression
256
What are characteristics for LCIS?
risk factor for invasive carcinoma, develops in 23-35% of women, similar to that of DCIS, but risk is high in both breasts, 3x more likely to be lobular carcinomas,
257
How can LCIS be treated?
bilateral prophylactic mastectomy, tamoxifen, or usually close follow up with screening
258
What are characteristics of ER+, HER2-, low proliferation subtype cancers?
majority of cancers in older women and men, detected at early age, cured with surgery, respond to hormone therapy but not chemo
259
What are characteristics of ER+, HER2-, high proliferation subtype cancers?
ER levels may be low and PR levels may be low or absent, most common association with BRCA2 mutations, show complete response to chemo, better prognosis than those that do not
260
What are characteristics of HER2+ subtype cancers?
second most common invasive subtype, half are ER+, half ER-, common in young white women and non white women, over half are related to Li-Fraumeni(TP53 mutation) syndrome and are the ER+ type, 1/3 respond to HER2 blocking Abs(trastuzamab)
261
What is the most common subtype of invasive cancer?
ER+ HER2- or luminal
262
Where do invasive breast cancers frequently metastasize?
bone
263
What are characteristics of ER- HER2- subtype cancers?
trpile negative or basal-like, common in younr premenopausal women and AA /hispanic women, typically BRCA 1 mutations, usually palpable as mass between mammographic screenings, share similarities with serous ovarian cancers, can express ER and HER2 in 10-15%, responsive to chemotherapy
264
Where is the HER2 gene located?
chromosome 17q
265
What morphology is seen with invasive carcinomas?
seen on mammograms with calcification are less than 1cm without density, have desmoplastic stromal reaction causing a unique sound on sectioning like cutting a water chestnut, larger carcinomas may penetrate the pectoralis muscle of cause skin dimpling, graded using Nottingham Histologic Score
266
What is the Nottingham Histologic Score grading?
Grade I- tubular pattern with small round nuclei and low proliferation(well-differentiated),
Grade II- tubule formation or solid clusters with single infiltrating cells(moderately differentiated),
Grade III- ragged nests or sheets with enlarged irregular nuclei, high proliferation(poorly differentiated)
267
What morphology do ER+. HER2- carcinomas present with?
mostly well differentiated, but can be poor or moderate, mucinous, papillary, cribriform and lobular patterns, all are special types
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What morphology do HER2+ carcinomas show?
poorly differentiated, no sepcific morphology, 50% apocrine and 40% micropapillary, associated with DCIS more than other types
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What is the morphology related to ER-, HER2- carcinomas?
poorly differentiated, circumscribed pushing borders with fibrotic center or necrotic center, some have lymphocytic infiltrate and are carcinomas with medullary features, not usually related to DCIS
270
What are characteristics of lobualr carcinoma subtype?
CDH1 loss(E-cadherin), discohesive cells, no desmoplastic response, metastatic spread into the peritoneum, GI tract, uterus and ovaries, high risk of signet ring gastric carcinoma
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What are characteristics of medullary carcinoma?
BRCA1 mutation associations, lymphocytic infiltrates are better prognosis and better chemo response,
272
What are characteristics of micropapillary carcinomas?
anchorage independent growth, express E-cadherin and stick to each other but not thestroma
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What morphology is seen in lobular carcinoma?
hard irregular masses, minimal desmoplasia(CHD1 mutation), signet rings with intracytoplasmic mucin deposits
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What morphology is seen with mucinous(colloid) carcinoma?
rubbery like blue-gray gelatin, pushing borders, clusters floating in mucin,
275
What is the morphology of tubular carcinoma?
well-formed tubules, mistaken for benign sclerosing lesion, cribriform pattern with apocrine snouts and some calcifications, assocaited with flat atypia, ALH, low-grade DCIS or LCIS
276
What morphology is seen with papillary carcinoma?
true papillae, fronds of fibrovascular tissue lined by tumor cells,
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What 2 special histologic types of carcinoma overexpress HER2?
apocrine carcinoma which resembles sweat glands with abundant eosinophilic cytoplasm,
micropapillary carcinoma which forms hollow balls of cells floating within intercellular fluid which mimic true papillae
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What morphology is seen in medullary carcinoma special type?
ER-, HER2-, soft to do minimal desmoplasia, solid syncytium-like sheets of cells with pleomorphic nuclei and prominent nuleoli which correspond to 75% of the tumor, frequent mitotic figures, lymphoplasmacytic surrounding and pushing borders, minimal DCIS
279
What is the morphology of secretory special type carcinoma?
ER-, HER2-, mimics lactating breasts by forming dilated spaces with eosniophilic material
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What is the morphology of inflammatory carcinoma?
extensive invasion and proliferation within lymphatic channels, casuing swelling, high grade
281
What are characteristics of male breast cancer?
risk is 1st degree relatives with breast CA, exogenous estrogen exposure, radiation, infertility, obesity, Klinefelter syndrome, age of 60-70 yo at Dx, BRCA2 mutations are common, ER+ is more common, usually palpable as subareolar and are more often invasive due to less breast tissue,
282
What is the most important prognostic factor without distant metastases
axillary lymph node metastases
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What is the prognosis for inflammatory carcinomas?
very poor, breasts with erythema and skin thickening, near the skin can cause peau d'orange
284
What is peau d'orange and what does it suggest?
dimpled breast tissue due to lymphatic congestion by a tumor
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What two tumors arise from intralobular stroma?
phyllodes tumor and fribroadenoma
286
What are characteristics of fibroadenoma?
most common benign tumor of female breast, present in 20-30s, frequently bilateral and multiple, palpable mass, hormonally responsive and increase with pregnancy, polyclonal hyperplasias of intralobular stroma, can be caused by cyclosporin A for renal transplant, proliferative changes without atypia, mild increase risk of breast CA,
287
What morphology is seen in fibroadenomas?
well circumscribed, grayish white, biulge above surrounding tissue and have slit-like spaces, delicate and myxoid stroma resembles normal intralobular stroma, surround by stroma(pericanilicular) or compressed and distorted(intracanilicuar)
288
What are characteristis of Phyllodes tumor?
arise from intralobular stroma, peak in 6th decade 20 years after fibroadenomas, are benign but have been called cytosarcoma phyllodes, assocaited with clonal acquired chromosomal changes(gain in 1q), and HOXB13 overexpression is higher grade and more aggressive
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What is the morphology of phyllodes tumor?
bulbous protrusions(leaf-like), due to nodular presence of stroma covered by epithelium which can extend into cytic space
290
How is phyllodes tumor different from fibroadenomas?
higher cellularity, higher mitotic rate, nuclear pleomorphism, stromal overgrowth, and infiltrative borders.
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What are the benign tumors of interlobular spaces?
have no epithelial component, myofibroblastoma-consists of myofibroblasts and is the only tumor which is equally common in males, lipomas-fat containing nodules, firbromatsosi-combination of myofibroblasts and fibroblasts, irregular infiltrating mass that can involve muscle and skin, possibly trauma associated, or from syndromes like FAP, Gardner and HDS
292
What are the malignant interlobular stroma tumors?
any stromal sarcoma, the most frequent of which is angiosarcoma, sporadic or therapy complication, around 35yo, are high grade and have poor prognosis, arise secondary to radiation or edema
293
What lymphoma can develop in the breast?
non-Hodgkin lymphoma, primarily B cell but can be T cell related, due to scar tissue from breast implants, young women with Burkitt can have bilateral massive breast enlargement and are pregnant or lactating
294
What ovarian tumors are most commonly bilateral?
malignant serous tumors, enometrioid tumors, clear cel carcinoma, and metastatic disease
