theory Flashcards
(125 cards)
1
Q
What is the utility of PAX8 in ascitic fluids?
A
- Positive in GU/Mullerian origin tumors
2
Q
What are the gross and microscopic features of ovarian polycystic disease?
A
Gross: rounded, slighty enlarged ovaries (bilateral) with multiple small subcortical follicles/cysts with similar size
Micro: thick, fibrous ovarian capsule, hyperplastic ovarian storma, no stigmata of prior ovulation
3
Q
List the non-neoplastic cysts found in the ovary, and briefly describe the histology
A
Epithelial inclusion cyst: single layer, flat to cuboidal +/- cilia. <1.0 cm (serous cystadenoma if >1cm)
Follicular cyst: 2.5-10cm, unilocular, inner layer of granulosa cells and outer layer of theca cells.
Corpus luteum: linted by luteinized granulosa cells with outer layer of luteinized theca cells.
Endometriotic cyst: endometrial glandular epithelium lining cyst, underlying endoemtrial stroma or hemosiderin laden macrophages (2/3)
Polycystic ovarian disease: fibrous capsule hyperplastic ovarian stroma +/- luteinization, often no corpora albicantia
Hyperreactio luteinais: multiple folllicular cysts with luteinized hteca/granulosa layers, edema within stroma and theca
4
Q
List the histologic types of surface epithelial neoplasms of the ovary
A
Serous (benign, borderline, malignant)
Endometrioid (bbm)
Clear cell (BBM)
Mucinous (BBM)
Brenner (BBM)
Mixed (BBM)
transitional carcinoma
Undifferentiated
SCC
5
Q
What’s the importance of histologic classification for epithelial ovarian neoplasms?
A
- Present at different stages
- Require different treatment
- Differing responsees to chemo
- different prognosis/survival rate
6
Q
Describe the staging for ovarian tumors using FIGO/TNM
A
Figo/TNM are the same except for 2 things: Fibo uses roman numerals, and IV in FIGO=M1 in TNM
1-Limited to ovaries; a=one ovarie, b=both ovaries, c=limited to ovaries, but with capsule rupture/surface/malignant ascites
2-one/both ovaries with pelvic extension/implants; a=uterus/tubes, b=other pelvic tissue, c=pelvic extension/implants AND + cells in ascites/wash
3-one/both ovaries with microscopic confirmed peritoneal spread outside of pelvis; a=microscopic beyond pelvis <2cm, b=macroscopic >2cm, c=>2cm or regional LN met
4/M1=distant mets
7
Q
What is the most common histologic type of familial ovarian carcinoma, and what common mutations are associated?
A
- High-grade serous is most common familial
- BRCA1/2
8
Q
What types of serous ovarian lesions are there? What are the defining histologic features?
A
Serous cystadenoma/cystadenofibroma: cystic with broad papillae, single layer of ciliated to cuboidal/columnar lining cells similar to fallopian tube
Serous borderline tumors: papillary branching with increased epithelial complexity, stratifiecation with tufting. Mild to moderate cytologic atypia. Microinvasive if <3mm or 10mm2
SBT with micropapillary pattern: long, non-branching, nonhiercharchal papillae with narrow stromal core. Cribriform pattern possible.
Serous carcinoma:
Low grade: papillary or micropapillary, with stromal invasion. Psammomma bodies. Low mitotic rate. No signifiant nuclear pleomorphism.
High grade: heterogenous patterns including complex papillary, solid, glandular. High grade nuclei, Markedly high mitotic rate
9
Q
What is the management for the varioustypes of serous ovarian neoplasms?
A
benign: unilateral oophorectomy
borderline: SBT with/without non-invasive implants=no further tx. If implants, needs further staging/tx
Carcinoma: full staging, post-op chemo. May receive neoadjuvant chemo.
10
Q
What are 3 conditions associated with maternal diethylstilbestrol use
A
- vaginal adenosis
- clear cell adenocarcinoma (aka mesonephroid adenocarcinoma)
- transverse vaginal or cervical ridges
11
Q
What are the morphologic and IHC featurs of clear cell adenocarcinoma of the vagina?
A
- Presents in adolescents, young adults (<30)
- Tubules, cysts, solid areas and papillary structures lined by clear cells. Variable mitoses. Abundant clear cytoplasm due to glycogen; hobnail cells protruding into lumen.
- Ddx microglandular hyperplasia, arias-Stella
- IHC: CK7, Cam 5.2, 34BE12, CEA, CD15, BCL2, Ca125; ER is variable, PR is negative.
12
Q
COmpare and contrast vaginal rhabdomyoma and botryoid rhabodmyosarcoma
A
Rhabdomyoma: found in adults. interweaving haphazard spindle-strap cells with cross-striations. No mitoses. No cambium layer
Rhabdomyosarcoma: kids under 5. undifferentaited round cells and spindle cells with some raquet/strap cells. Cells crowd around blood vessels. Cambium layer formation. Foci of neoplastic cartilage can be found. Tx with chemotherapy/surgery.
13
Q
List 4 types of glandular hyperplasia in the cervix and the histologic features
A
Microglandular hyperplasia: complex proliferation of small glands lined by flat epithelial cells without atypia; related to squamous met. May show solid areas, pseudoinfiltration, signet cells, occ. mitoses. CEA negative.
Atypical reactive proliferation: following endometrial samplikng. Short micropapillary processes, squamous met, hobnail cells, mild atypia.
Diffuse laminar endocervical glandular hyperplasia: non-neoplastic, proliferation of medium sized, even spaced well diff glands in inner 1/3 with chronic inflammation.
Lobular endocervical glandular hyperplasia: lobular proliferation of medium sized glands centered around large gland. Gastric mucin. NO desmosplasia or atypia.
(other conditions: mesonephric rests, nabothian cysts, tunnel clusters)
14
Q
what are the features of a placental site nodule?
A
- Well-defined hyalinized lesion located immediately beneath mucosa
- intermediate trophoblasts exhibiting cytoplasmic vacuolization
- positive for cytokeratins and HPL
15
Q
What are some features of cervical adenoma malignum?
A
- minimal deviation adenocarcinoma
- not HPV associated
- distorted glands with irregular outlines deep in the cervix with desmoplastic response (at least focally)
- Look for vascular/perineural invasion
- Are CEA positive, p16/p53 negative
- Associated with Peutz-Jeghers, STK11 tumr suppressor gene mutations
16
Q
Name some forms of endometrial metaplasia
A
- Squamous metaplasia
- Ciliated (tubal) metaplasia
- papillary metaplasia
- mucinous metaplasia
- eosinophilic metplasia
- clear cell/hobnail metaplasia
- intestinal metaplasia (rare)
- arias stella rxn
stromal metaplasia
17
Q
A
review mixed epithelial/mesenchymal
18
Q
Serous ovarian neoplasms: what is the prognosis associated with each type?
A
Benign: 100%
Borderline: depends on presence of implants; invasive implants give a survival comparable to lg serous
Malignant: poor, typically presents at advanced stage. LG recur over a long time period; high grade progress more rapidly. LG are less responsive to chemotherapy.
19
Q
What is the significance of peritoneal implants in SBTs?
A
- 2 types: non-invasive (epithelial, desmoplastic) and invasive
- non-invasive SBT implants have 100% survival
- SBTs with invasive implants have increased recurrence rates, survival comparable to low grade serous carcinoma
20
Q
What is the significance of finding SBT in lymph nodes?
A
- upto 1/3 of pts with SBT have it within lymph nodes if they undergo lymphadenectomy
- requires exclusion of endosalpingiosis, psammomatous calcs, nodal mesothelial hyperpalsia and metastatic low grade serous carcinoma
- definitive SBT in LN is associated with more frequent invasive/non-invasive implants, but not an independant prognostic factor
21
Q
What gross features suggest a diagnosis of serous carcinoma of ovary vs. primary peritoneal?
A
- Do a complete gross examination of ovary: location of tumor, surface involvement, capsule intactnes, size of tumor deposti, sample solid areas
- Examine fimbriated ends of fallopian tubes (amputate distal fimbriae, cross section of tube every 2mm, submit in totatl)
- For peritoneal deposits, measure size and document location
- Primary site is determined based on location of bulk of lesion and size of deposit. A unilateral or bilateral ovarian mass, with parenchymal and surface involvement AND tubal STIC presumes ovarian origin
- If both ovaries are normal sized, involvement of peritoneal site > ovarian, and ovarian invovlement is surface only (or less than 5 x 5mm), favour peritoneal
- keep in mind primary peritoneal much less common
22
Q
What are precursor lesions for low and high-grade serous carcinoma?
A
Low grade: serous borerline tumors
HIgh-grade: Serous tubal intraepithelial carcinoma. Fallopian tube epithelium with loss of polarity, crowding, stratification, increased N/C ratio with hyperchromasia. IHC: p53+, increased Ki67.
23
Q
Classification of endometrioid lesions in ovary?
A
Benign, borderline, malignant
24
Q
What is a benign finding associated with endometrioid neoplasms in ovaries and how are endometrioid adenocarcinomas of ovary graded?
A
- Benign association: endometriosis
- Grading: not standardized, but usually graded like FIGO grading of endometrial endometrioid adenocarcinomas
25
Describe the morphologic criteria for each type of endometrioid neoplasm of ovary
cystadenoma/fibroma: branching angular glands/cysts, usually resembling those of proliferative or minimally hyperplastic endometrium
borderline: spectrium of epithelial proliferation, glandular crowding, and cytologic atypia resembling hyperplastic endometrium; can have rare areas of microinvasion/intraepithelial carcinoma
adenocarcinoma: looks like endometrioid adenocarcinoma of endometrium. Confluent/expansile growth wtih extensive glandular branching, budding, cribriform architecture and complex papillary proliferation. Destruction/invasiion.
26
List the molecular alterations found in endometrioid adenocarcinoma
CTNNB1 (B-catenin)
PTEN
PIK3CA
MLH/mismatch repair
P53 in some high-grade
27
What is the prognosis associated with each type of endometrioid neoplasm of ovary?
Benign/borderline: excellent
Malignant: better than serous generally; higher proportion of endometrioid present at earlier stage. Survival depends on stage; 5 yr survival for stage 1 is \>75%, vs \<10% stage 4
28
List the different types of clear cell tumors of ovary, name one benign finding
- B, B (rare), M
- endometriosis
29
What are the morphologic features of clear cell carcinoma of ovary?
- Variety of patterns: solid, papillary, tubulocystic, mixed
- hobnailed cells with relatively uniform hyperchromatic nuclei and prominent nucleoli
- clear/eosinophilic cytoplasm with relatively low mitotic rate
- presence of hyaline globules or psammoma bodies
30
Describe the differential diagnosis of clear cell carcinoma
- Serous carcinoma
- Endometrioid carcinoma with clear cell changes
- Yolk sac tumor
- Dysgerminoma
- Metastatic clear cell carcinoma from an extraovarian site
31
Mucinous neoplams of the ovary: how should you handle a mucinous ovarian mass at the time of FS and grossing?
FS:
- measure specimen, inspect capsule for integrity, record surface lesions or rupture, can selectively ink outer surface
- cut/open as many cystic components as possible
- examine for solid/papillary areas and submit several sections for F/S
Grossing:
- submit 1-2 blocks/cm of greatest dimension, focusing on solid areas'
- submit fallopian tubes
- sample omentum, uterus (endometrium, endocervix), opposite ovary and appendix
32
What's the significance of a diagnosis of ovarian mucinous neoplasm to the surgeon at the time of FS?
- dictates what type of surgery to proceed with
- additional staging
- assessment of appendix, looking for other mets
33
What are the morphologic features of an ovarian mucinous borderline tumor, list the ddx.
- No invasive component/microinvasion only
- Complex and stratified mucinous lining (endocervical, mucin poor, goblet cell type).
- Papillary protrusions possible
- Mild/moderate cytologic atypia. Bascially looks like a tubulovillous adenoma of colon.
- DDx: adenocarcinoma, primary or secondary
34
What are 2 types fo mucinous borderline tumors of ovary. How do they differ?
- INtestinal type, endocervical type
- Endocervical/sero-mucinous: is less common, smaller, more frequently bilateral, more often associated with endometriosis
- Often has inflammatory infiltrate and may be mixed with endometrioid neoplasm
35
If you have bilateal ovarian mucinous tumors, what is the ddx? what are sources of mets to the ovary
- Ddx: primary ovarian vs mets
- Sources of mets: GI (appendix, stomach, pancreas, colon); breast, endometrium, endocervix
36
Describe how you would differentiate a primary ovarian tumor from a met
Features favouring primary ovarian:
* unilateral
* one large mass \>10cm
* mainly parenchymal involvement
* no hx of other lesions
* IHC "compatible"
Features favouring met:
* bilateral
* multiple small foci or single cells infiltrating parenchyma, bulk on surface
* extensive LVI
* pools of mucin (esp. appendix, but also 2ndary malignancy from teratoma)
* hx of other malignancy
* histologic features-eg. dirty necrosis
* IHC patterns not in keeping with ovarian such as GI, breast, lung
37
What are some risk factors for epithelial lesions of the ovary?
- BRCA1/2 mutations
- Family hx
- Childhood gonadal dysgenesis
- clomiphene use
- estrogen replacement therapy
- nulliparity
- advancing age
- Lynch syndrome
38
What are some protective factors in epithelial ovarian neoplams?
- OCP use
- fimbreaectomy
- tubal ligation
- prophylactic oophorectomy
- early pregnancy \<25
39
What are the 2 proposed pathways for serous neoplasms of the ovary?
- Type 1 lesions: includes low-grade serous, mucinous, endometrioid
- follicular rupture at ovarian surface leads to epithelial inclusion cysts. Overtime, genetic mutations accumulate leading to dysplasia. KRAS mutations associated twith mucinous/lg serous, BRAF with LG serous and PTEN with endometrioid.
Type 2 lesions: These develop from serous tubal intraepithelial carcinomas in the fimbriae of fallopian tube; deposits on ovarian surface. p53 mutations.
40
In the staging of ovarian epithelial neoplasms, what is the significance of liver metastases
- Liver capsule only= stage 3
- Liver parenchyma=stage 4
41
What is the breakdown for serous epithelial neoplams Be/Bo/M in terms of % and bilaterality?
Be: 60%, bilateral in 6-20%
Bo: 10-15%, bilateral in 25-40%
M: 30%, bilateral in 65%
42
What is the % of atypia (architecture or cytological) to qualify a neoplasm as borderline in the ovary?
-10%
43
What is the definition of micropapillary pattern in SBT and what is the inplication?
- 5mm extent papillae 5x longer than wide; may show cribriform, nuclear atypia, have "medusa head" configuration
- Found in 5-10% SBT, more commonly bilateral, more commonly have surface involvment, have extraovarian implants and are RESISTANT TO CHEMO
44
What is microinvasion in SBT?
Small stromal foci of single cells or cribriform aggregates with minimal stromal rxn
size criterion: \<3mm in linear extent or \<10mm2
Doesn't affect prognosis (i.e. cal SBT with microinvasion)
are allowed multiple foci
45
What are ovarian autoimplants in SBT?
- implants look like desmoplastic implants elsewhere but on ovary
- FOund between papillae on surface, have more stroma than epithelial component
Borderline appearance of cells
no impact on survival
46
What are prognostic factors in SBT?
- Stage
- Macroscopic residual disease
- Microinvasion/micropapillary features, extraovarian implants
- transformation to LG or HG serous CA
47
Compare and contrast the features of LG and HG serous ovarian carcinoma
LG: younger, 1/3 with SBT. Have large papillae, micropapillary pattern, psammomacarcinoma pattern.
PsammomaCA: \>75% calcs, moderate atypia, no solid areas.
Overall not very chemoresponsive; multiple recurrences over time
HG: age group spans from reproductve--\>post menopausal, presents at late stage III-IV. Terrible survival-9% 5 yr survival stage 4 (compared to 75% stage 1). Often bilateral. IHC: p53, p16, WT1+
More chemoresponsive, but aggressive.
48
What is the Silveberg grading system in ovarian epithelial ovarian neoplasms?
- Scoring based on architecture, nuclear grade and mitoses (although chemo can affect it)
- Grade 1 (3-5), Grade 2 (6-7), Grade 3 (8-9)
Architecture: glandular (1), papillary (2), solid (3)
Nuclear grade: mild (1), mod (2), severe (3)
mitoses/10HPF: 0-9, 10-24, \>25
49
Mucinous ovarian tumors: what is the breakdown of Be, Bo, M
Be: 80%, Bo: 10%, M: 10%
50
What are mural nodules in mucinous neoplasms of the ovary?
Can be seen in be/bo/m mucinous neoplasms
Ddx between sarcoma-like nodule and anaplastic CA
Features favouring sarcoma-like nodule: many small lesions, circumscribed, heterogenous cell population, spindle cells, marked inflammation, no CK staining
Features favouring anaplastic CA: single large nodule, not circumscribed, homogenous population (of ugly cells), no spindle cells, no marked inflammation, at least weak CK staining
51
What are some possible architectural patterns seen in endometrioid lesions of the ovary?
- glandular, villoglanduar, sertoli-form, trabecular, hyalinzed stroma, spindle cell diff, squamous ce etasplasia microfollicular, secretory
52
Clear cell neoplasms of ovary: give some features
- Most are carcinoma
- 5-7th decade, unilateral
- HIGHEST ASSOCIATION WITH ENDOMETRIOSIS
- associated with hypercalcemia and trousseau's phenomenon
- 5% 5-yr survival for stage 4, poor chemo response
53
What is the typical IHC pattern of a brenner tumor? How can you differentiate a brenner tumor from a transitional tumor?
IHC: CK7+, WT1+ (20 neg, thrombo/uroplakin -)
To call malignant brenner: should see a benign/borderline brenner component somewhere in lesion
\*\*\* benign brenners associated with mucinous neoplasms
54
What are the features of adult granulosa cell tumors?
- Pts are middle-aged, post-menopausal females
- present with amenorrhea, or abnormal uterine bleeding
- tumors frequently estrogen secreting, increased risk endometrial hyperplasia/CA
- 90% 10 yr survival with stage 1; frequent recurrences within pelvis
Gross: unilateral, solid + cystic component, soft yellow tan and hemorrhagic
Micro: varied patterns including cords, trabeculae, insular, diffuse, solid, tubular, microfollicular, macrofollicular, watered silk, gyriform, pseudopapillary.
Granulosa cells: monomorphic, coffe bean (grooves) with call exner bodies
molecular: FOXL2 mutation
55
List the DDX of adult granulosa cell tumors
- Poorly differentiated/undifferentiated carcinoma
- Endometrioid adenocarcinoma
- Small cell carcinoma
- ENdometrioid stromal sarcoma
- Thecoma/cellular fibroma
- Stromal tumors with sex cord elements
- Large luteinized follicle cyst of pregnancy
- Yolk sac tumor
56
How can you differentiate AGCT from carcinomas, based on clinicopathologic findings
AGCT: unilateral, indolent course, low stage, cell nuclei are uniform, pale, grooved. Low mitotic count.
IHC: inhibin +, WT1+, CD1-+, FOXL2+
Carcinoma: bilateral more frequent, rapid course, high stage, cell nuclei are hyperchromatic, pleomorphic. High mitotic count + atypical mitoses. IHC: WT1 +/-, inhibin -, CD10-, FOXL2-
57
What differentiates AGCT from JGCT:
ACGT: older pt, nuclei uniform, pale, grooved. Cal-exner bodies, no immature follicles. Low mitotic rate.
JGCT: 50% prepubertal, rare \>30 yrs. Wide variation in nuclear atypia, hyperchromasia, grooving. Immature follicles prsent, rare call-exner bodies. Variable mitotic rate but higher than AGCT.
58
List a DDX for spindle cell lesions of the ovary, including clinical and microscopic findings.
FIbroma: commonly middle-aged, but any age. Associated with MEIG syndrome (ascites, L-sided pleural effusion) and ghorlin syndrome. Spindle cells arranged in intersecting bundles, no cytologic atypia. If cellular fibroma can have increased mitotic rate.
Fibrosarcoma: very rare. Uniform hypercellularity, significant atypia, conspicuous mitoses.
Thecoma: older age, unilateral. Sheests of cells with fibrous bands and hyalinization. Cells aroe oval/round with ill defined borders and abudant cytoplasm. Luteinized form possible.
Sclerosing stromal tumor: 2nd-3rd decade, ER/AR secreting. Pseudolobular, cellular and fibrous areas, vacuolated cells.
Signet-ring stomal tumor: adults, benign. Spindled and signet-ring tumor.
Microcystic stromal tumor: adults. Lobulated regions with small cysts.
59
You discover an immature teratoma at the time of FS. WHat do you tell the surgeon?
- Indicate immature component seen, provide a grade (if possible)
- Indicate any other germ cell component
- Dicuss further management, since immature component considered malignant (i.e staging)
60
What is the most likely immature component in a teratoma, and how do you grade them?
- Immature neural tissue is most comon
- Grade based on amount of immature neural tissue; Grade 1: rare immature neural tissue \<1 low powered field on any slide
Grade 2: imamture neural tissue in 1-3 lpf on any slide
Grade 3: immature tissue in \>3 lpf
- increased immature component=poor prognosis
stages 2/3 treated with chemothearpy
61
What do you include in the final report on an immature teratoma
- Size of tumor
- immature component, grade
- presence of other germ cell components
- prescence of other maligancy arising from teratoma
- capsular involvement/intactness
- involvement of other extraovarian sites
- LN status (if staging was done)
62
List some types of malignancies arising from teratomas
- SCC is most common
- also reported: adenoCA (colonic type), mucinous carcinoma, papillary thyroid, melanoma, BCC, chondrosarcoma, leiyomyosarcoma, angiosarcoma
63
List tumors (other than teratomas) that can have heterologous elements in the genital tract
- Carcinosarcomas (MMMT)
- Endometrioid adenocarcinoma
- Adenosarcoma
- Sertoli-Leydig tumor
64
List the different histologic patterns seen in yolk sac tumors
- Microcystic/reticular
- endodermal sinus
- solid
- glandular/alveolar
- poyvesicular vitelline
- myxomatous
- papillary
- macrocystic
- hepatoid
- glandular/primitive endodermal
65
List IHC markers to help distinguish yolk-sac from other germ cell tumors
Yolk sac: AFP+, Cam 5.2+, glypican 3+, Sal4+
dysgerminoma: OCT4+, CKIT+, D240+
Embryonal carcinoma: OCT4+, CAM 5.2+, CD30+, SOX2+
66
How can you differentiate yolk sac tumors from clear cell carcinoma of the ovary?
Both share similar tubular patterns with clear cytoplasm and hyaline globules
YST: no association with endometriosis, various patterns, Schiller-Duval bodies, AFP+, SLA4+, CK7-, EMA-
CCC: more regular tubular pattersn, papillary, solid, hobnail cells. No schiller-duval. AFP-, CK7+, EMA+, HNF1B+
67
Ovarian germ cell tumors: Review clinical, gross, microscopic.
**Mature teratoma:** most common germ cell neoplasm. Most in reproductive age group. TYpical dermoid cyst appearance, rarely solid. Micro: usual skin lining and other structures, 3 germ-cell layers. Good prognosis after excision, complications include torsion/rupture, malignancy developing within.
**Immature teratoma:** uncommon, usually in 1-2nd decade. Large, unilateral, solid/cystic. Areas of immaturity, may be in combination with other germ-cell types. Malignant with rapid growth.
**Dysgerminoma:** most common malignant germ cell neoplam of childhood/adolescence, usually 2-3rd decade. Large tumor, R\>L, solid w/tan surface. Micro: uniform polygonal cels in sheets/groups with infiltrating lymphocytes. Rare synctiotiotrophoblasts. Malignant; mets and local. Responds to chemo; good 5 yr survival \>75%.
**YST:** 2nd most common malignant GCT 2-3 decade. AFP may be elevated. Unilateral, solid/cystic gray-yellow. Many micro patterns, Schiller-Duval bodies, PAS+ globules. Malignant; early mets, good response to chemo.
**Embryonal:** in kids/young adults. Solid grey mass + necrosis/hemorrhage. SOlid sheets/pseudoglandular, large cells w/eosinophilic cytoplasm, mitotically actve. Malignant and locally aggressive.
**Chorio:** young, elevated B-HCG, can present with thyrotoxicosis. Unilateral, grey w/hemorrhage. Cytotrophoblasts, intermediate trophoblast, synctitiotrophoblasts. Malignant, widely metastatic. Good chemo response.
**Mixed:** More than 1 germ cell component. Prognosis variable, but most aggressive ones usually determine it (eg. chorio)
**Polyembryoma:** rare! in young people! AFT/B-HCG can be elevated. Unilateral, solid mass + necrosis. Embryoid bodies resembling embryonic disk, associated with teratomas. malignant, extensive mets. Chemoresponsive.
68
List common sites involved by endometriosis
Ovaries, uterine ligaments, rectovaginal septum, pelvic peritoneum, laparotomy scars
69
Outline 3 theories regarding pathogenesis of endometriosis
regurgitation/implantation theory: retrograde menstruation through fallopian tube out into peritoneum, cervical mucosa
metaplastic theory: arises from coelomic epithlium, from which mullerian ducts/endometrium originate. Metaplasia of serous lining.
vacular/lymphatic dissemination: pelvic veins/lymphatics spread to lungs/LN
70
Name tumors associated with endometriosis
- Endometrioid adenocarcinoma
- Clear cell carcinoma (highest association!)
- Seromucinous borderline tumor
- Adenosarcoma
71
Extrammamary pagets: list possible sites, morphologic features, ddx and IHC
Sites: vulva, perineum, anus, scrotum, axilla
Histo: cells in singles/nests within epidermis/skin appendage. Halo around cells. Finely granular cytoplasm, mucin+. +/- underlying malignancy
DDx: SCC skin (including clear cell variant), melanoma, merkel cell CA, colorectal CA, urothelial CA, bowenoid papulosis
specials/IHC: mucin+, CK7+, EMA+, CEA+, B72.3+, GCDFP15+ (may be HER2+)
S100, HMB45 an CK20-
72
Give 4 primary non-squamous neoplasms of vulva
- Embryonal rhabdomyosarcoma, botryoid type
- Melanoma
- Basal cell carcinoma
- Aggressive angiomyxoma
- Angiomyofibroblastoma
- Extrammamary paget's
73
List 4 complications associated with IUD
- actinomyces infection
- uterine perforation/laceration
- endometritis
- squamous metaplasia/cytologic abnormalities on pap smear
74
List the types of endometrial metaplasia
- tubal
- squamous
- eosinophilic
- mucinous
- papillary
- clear cell
- hobnail
75
LIst some non-malignant causes of abnormal uterine bleeding (ie not 5 days during menses or after menopause)
- Pregnancy
- atrophy
- exogenous hormone use/hyperplasia
- anovulatory cycles
- chronic endometritis
- leiyomyomata
- inadequate luteal phase
76
List some causes of hyperestrogenic states
- exogenous estrogens
- endogenous hyperestrogenism (ovarian, central)
- obesity
- estrogen secreting tumor
77
Classify endometrial hyperplasia and give risk of developing malignancy
Simple
* without atypia-1%, with atypia 8%
Complex
* without atypia-3%, with 29%
78
What is EIN? what are the diagnostic criteria?
Endometrial intraepithelial neoplasia, thought to be precursor lesion of endometrioid adenocarcinoma.
Same molecular findings (PTEN mutations)
\>1mm, architectural complexity and nuclear features different from background normal endometrium (i.e. enlargment, hyperchromasia...)
- must exclude benign mimicks and carcinoma prior to making diagnosis
- good correlation with complex atypical hyperplasia (~70)
79
What is the ddx of endometrial hyperplasia, and how can you distinguish hyperplasia from well differentiated carcinoma?
DDx: well-diff adenocarcinoma, secretory endometrium, endometrial polyp, metaplasia, endometrial gland/stromal breakdown, artificial crowding due to telescoping glands, biopsy compaction etc.
Adenocarcinoma: higher complexity, back-to-back glands and stromal change .Cytology: increased nuclear pleomorphism/nucleoli may be present.
80
Give the histologic classification fo endometrial adenocarcinoma
Endometrioid (w/squamous, villoglandular, secretory, ciliated), mucinous, serous, clear cell, mixed, SCC, small cell, undifferentiated
81
How do you grade endometrial tumors?
Endometrioid: FIGO grading system based on % of solid/microglandular component: Grade 1: \<5% solid, Grade 2 5-50% solid, Grade 3\>50% solid
\*\*\* squamous/spindle areas don't count
Serous: are high grade
Clear cell: are high grade
Small cell: are high grade
82
What are 3 types of endometrial carcinoma associated with a poor prognosis?
- Serous, Clear cell, undifferentiated carcinoma
83
What are 4 pathologic prognostic factors in endometrial carcinoma when it's limited to uterine corpus
- Histologic type
- Histologic grade
- Lymphovascular invasion
- Depth of myometrial invasion
84
What are 5 factors used as staging criteria in endometrial carcinoma?
- uterine serosal involvement
- depth of myometrial invasion
- cervical stromal involvement
- presence of extrauterine tumor involvement
- lymph node involvement
85
How does staging guide management for endometrial carcinoma?
- Post-op chemorads given to high-risk tumors (i.e. if deeply invading myometrium, or involvement of cervix, esp. if Grade 2 or higher)
86
What hereditary syndromes can cause familial endometrial adenocarcinoma?
Lynch syndrome: caused by DNA mismatch repair abnormalities (MSH2 +- MSH6, MLH2, PMS2)
Usually associated with endometrioid type, small # of clear cell.
Cowden syndrome: PTEN mutations (tumor suppressor).
87
What is currently a precursor lesion for endometrial serous carcinoma? LIst histologic and IHC
- Controversial.
- Endometrial glandular dysplasia: supposedly early lesion; p53 strongly staining due to p53 mutations. Moderate Ki67. Some nuclear features (enlargment, hyperchromasia) and stratification, but not "full-blown" EIC. No definite outcome studies.
- EIC: serous carcinoma limited to epitheliuml on surface of polyp or lining glands in a background of atrophic endometrium. Significant nuclear atypia, identifcal to invaisve, with increased mitotic activity. Not really "in-situ" since has the ability to metastasize.
88
What is the ddx of polypoid lesions in the endometrial cavity
- Benign endometrial polyp
- Atypical polypoid adenomyoma
- Adenosarcoma
- Polyp with area of carcinoma
- Carcinosarcoma
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HOw does atypical polypoid adenomyoma behave clinically? What are the implications of the diagnosis?
- Occurs in pre-menopausal, nulliparous females, associated with infertility
- HIgh recurrence rate if incompletely excised
- Pts have increased risk of developing endometrioid adenocarcinoma (~30%)
90
Leiyomyomas: What translocation is present? What different types of leiyomyomas are there?
- recurrent t (12:14) HMGA2-RAD51b
- types: cellular, mitotically active, atypical/symplastic, epithelioid, myxoid, lipoleiyomyoma, vascular, schwannoma-like, intravascular...
91
How do you differentiate leiyomyoma from leiyomyosarcoma based on gross and microscopic features
Leiyomyoma:
- usually smaller, often multiple, sharply circumscribed, firm, white whorled surface, may rarely have pink-brown softening
- usually bland spindle cell lesion with intersecting fascicles and mitoses \<10/10HPF, no tumor necrosis
Leiyomyosarcoma:
- larger, single, poorly demarcated/infiltrative, hemorrhagic/necrotic, fish-flesh texture
- histologic criteria for malignancy depend on histologic type.
- spindle: true tumor cell necrosis, diffuse mod/severe atypia \>10 mitoses/10HPF
- epithelioid: criterion for mitoses \>5/10 HPF
- myxoid: significant cytologic atypia, with/without necrosis, any mitoses significant (b/c is less cellular)
- IHC favouring malignant: hi ki67, p53+, p16+
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Define STUMP
- Smooth muscle tumor of uncertain malignant potential
**Criteria: mitoses \<20, NO definite necrosis, focal moderate/severe atypia- Use this if:**
- uncertainty regarding type of smooth muscle differentiation
- Uncertainty of benign behaviour for a certain group of tumors due to lack of clinical info
- Uncertainty of mitotic index: may have marked atypia, unceratin or borderlinemitotic count and necrosis equivocal
- Uncertainty over presence/type of necrosis (or maybe just focal)
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Endometrial stromal tumors. Clasify and give histologic features of each types
Endometrial stromal nodule: well circumscribed, yellow/soft, solitary. Bland round/oval cells, arranged around hyalinized arterioles. Allowed 1-3 protrusions, 3mm maximum. No LVI allowed!
Endometrial stromal sarcoma (LG): poorly cirumscribed/demarcated, diffuse permeating growth, yellow soft surface. Looks like worms. Similar cytology to ESN, but more myometrial finger-like projecitons/permeative growth with LVI.
Undifferentiated endometrial sarcoma: Infiltrative, yellow/white. Pleomorphic spindle cell tumor with high grade nuclear features. No indication of stromal differentiation.
"HG ESS": coming back into acceptance. Is a higher-grade version of ESS, with more atypia. Very atypical areas found intermixed with LG-ESS.
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List IHC markers used to distinguish smooth muscle tumors from endometrial stromal neoplasms.
Endometrial stromal nodule/endometrial stromal sarcoma: CD10+, PR+, ER+, vimentin+ can show some focal staining for muscle markers.
leiyomyosarcoma: desmin, h-caldesmon; strong staining favours this.
Molecular genetics: ESN/ESS have t (7,17) JAZF1-JJAZ1 and JAZF1-FRHF1 translocations
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In combined epithelial-mesenchymal neoplasms of uterus, give classification and prognosis
Carcinosarcoma: poor prognosis. Is based on the differentiation of the epithelial component (usually serous)
Adenosarcoma: low malignant potential, but recurrences are poor prognostic indicators.
Carcinofibroma: very uncommon, uncertain prognosis. Likely based on epithelial component so stage, depth of invasion and histology.
Adenofibroma: both components are benign; may recur.
Adenomyoma: benign, may recur. See atypical polypoid adenomyoma.
96
Classify gestational trophoblastic disease
Molar lesions: complete hydatidiform mole, partial hydatifiorm mole
Non-molar lesions: placental site trophoblastic tumor, epithelioid trophoblastic tumor, choriocarcinoma
97
Compare and contrast complete and partial mole
Complete:
* empty ovum, diploid 46 XX or Xy
* markedly increased b-HCG
* snow-strom on U/S
* large edematous villi with circumferential trophoblastic proliferation, with trophoblastic atypia. No vessels/fetal parts or fetal RBCs
* does not express p57 in cytotrophoblast (control + in decidual cells), ki67 high
Partial:
* triploid 69 XXY or XXX
* normal/mod increase in B-HCG
* uterus small for dates
* 2 populations of villi: with scalopping, some trophoblastic proliferation, "geographic outlines"
* trophoblastic atypia absent
* fetal parts usually present
* p57+ in cytotrophoblast, ki67 high
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What is the underlying cause of a complete mole? Of a partial mole?
COmplete: fertilization of an empty ovum by 2 sperms, or by 1 sperm that duplicates. Genetic material is paternally derived.
Partial: normal haploid ovum is fertilized by 2 sperms with a haploid set of chromosomes or by a mutant sperm with a diploid set
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What is the tx for a molar pregnancy? What is the prognosis?
Evacuation, serial serum b-HCG levels x 6 months to monitor for development of persistent GTD
Risk of GTD: in complete mole, 17-20%, \<4% partial mole
Pts with complete moles are at increased risk of choriocarcinoma; 2-5% for complete, rare in partial.
Invasive moles are most common type of persistent GTD; may develop after complete/partial mole
Pts with a molar pregnancy can have normal reproduction afterwards, however should wait a sufficient period of time to monitor b-HCG levels.
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How can you differentiate hydatiform mole from hydropic abortus?
Clinical presentation, B-HCG levels, radiologic findings
Morphology: complete and partial moles have some degree of trophoblastic proliferation. Hydropic abortus has no significant trophoblastic proliferation or atypia.
IHC p57 is absent in cytotrophoblast of complete moles, is present in that of partial/hydropic abortuses. Use ki67 --\>not elevated in hydropic abortuses
Flow/ploidy analysis: partial moles are triploid. Can also use FISH for HER2 as a way of determining this.
DNA microsatellite marker analysis: look for maternal and paternal DNA.
101
What is the ddx for a single fragment of squamous cell carcinoma found in a gyne specimen (eg. products of conception)
- Endometrioid adenocarcinoma of endometrium with squamous metaplasia
- SCC of the cervix or other location in lower genital tract
- GTD including choriocarcinoma, epithelioid trophoblastic tumor (rare!)
- Contaminant from a different case (floater)
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What steps would you take to prove that a fragment of tissue on a slide is a contaminant?
- Cut additional sections (does it disappear?)
- Check the block to see if tissue fragment is embedded in block
- Review pt history/clinical notes
- Review cases grossed and cut at same station/day
- do DNA testing
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Describe the histologic and IHC features of placental site trophoblastic tumors
Histo: Large, pleomorphic implantation site intermediate trophoblast cells forming confluent sheets or single cells, with infiltrative borders. Fibrinoid deposits and dissection of smoooth muscle.
IHC: HPL ++++, CD10+, p63 negative, ki67\>10%
(vs placental site nodule--present on surface of endometrium or cervix. Focus of intermediate trophoblast cells surrounded by hyaline. Not proliferating but HPL+)
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What is the ddx of placental site trophoblastic tumors
- Exaggerated placental site/placental site nodule
- Choriocarcinoma
- Epithelioid trophoblastic tumors
- Epithelioid smooth muscle tumors
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What is the prognosis of PSTT?
- Most are self-limiting
- 10-15% are clinically malignant
106
PSTT vs ETT: compare and contrast
Similar presentation:
* Usually women ages 15-48 years
● Presents with abnormal vaginal bleeding or lung metastases
● Usually elevated beta hCG, but less than levels seen in choriocarcinoma
● Usually associated with prior hydatidiform mole or choriocarcinoma, up to 18 years prior clinical presentation.
Cell of origin is different-PSTT-implantation site intermediate trophoblast, ETT is placental intermediate trophoblast
IHC: PSTT is HPL+++, p63 neg. ETT is p63+ and PSTT neg.
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List different types of salpingitis, etiology, complications
Acute: young females, ascending infection by chlamydia or gonorrhea, may be polymicrobial. Leads to infertility/ectopic pregnancy. PID.
Chronic: resolving acute, may show hydrosalpinx.
Granulomatous salpingitis: TB, fungal, crohn, sarcoid. Leads to infertility, ectopic pregnancy.
Salpingitis isthmica nodosum: young females, ? etiology, infertility and ectopic pregnancy.
108
What is the appearance of LSIL on colposcopy, and what are methods to diagnose HPV infection?
- Colpo: acetowhite lesion, indicative of productive lesions
- Methods: pap smear/biopsy morphology
- IHC for p16 (+/- ki67)
- ISH
- DNA HPV testing (from pap or on FFPE tissue)
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Other than cervical lesions, what other areas demonstrate HPV disease?
- oropharyngeal SCC
- anal SCC
- other female genital tract lesions
- penile lesions
110
What are 3 HR HPV and 2 LR HPV
HR: 16, 18, 31, 34
LR: 6,11
111
Briefly describe the molecular pathogenesis of HR-HPV related malignancy
- 2 HPV viral proteins, E6 and E7 act to overcome activity of cell cycle inhibitors
- E6 binds to p53, inactivates it by enhancing its degradation through ubiquitin dependent proteolysis
- E7 binds RB, disrupting E3F/RB complex and promotes degradation of RB
- By knocking out p53, cell is allowed to proliferate with DNA damage and don't undergo apoptosis. Taking out p53 and RB allows for unlimited growth. p16 (CDK2A) accumulates as it is trying (in vain) to compensate for loss of RB and p53.
112
Invasive the different histologic types of invasive carcinoma of cervix. Which ones aren't associated with HPV?
- SCC (including warty, basaloid, verrucous)
- Adenocarcinoma
- Adenosquamous (poorly diff, aggressive)
- Adenoid cystic
- Adenoid basal cell
- Large cell neuroendocrine
- Small cell neuroendocrine
- Adenoma malignum (not HPV, Peutz-Jeghers)
- Clear cell carcinoma (not HPV, DES)
- Mesonephric carcinoma (not HPV)
113
List risk factors for SCC cervix
HPV, smoking, OCP, immunosuppression, multiple sexual partners/young sexual debut
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How do you define microinvasive scc cervix?
- depth: \<3mm stromal invasion
- lateral extent: \<7mm
- no LVI
(by definition is a microscopic lesion)
115
How do you gross a cone bx? How do you gross a radical hysterectomy?
Cone: orient, ink margins. Open and measure. Pin out to fix.
Serially section into wedge-shaped sections along long axis of cervical canal. submit in toto.
Rad hyst: orient, ink resection margins of parametrium/vaginal cuff. Assess margins for involvement.
- Amputate cervix with cuff, open at 12
- if tumor grossly identified, measure size, take representative blocks to demonstrate maximal depth. Consider submitting entire CA if small.
- Sample vaginal tissue and parametrium
- Look for LN
- Submit uterus/adnexa accordingly after inspecting for involvement/serosal deposits
- IF no tumor obvious, submit entire cervix like cone bix
- items to report histologic type/grade, tumor size (depth, horizontal) and include how many blocks involved
- multifocality, LVI, extension (uterine corpus/paracervical/vaginal), extension to adjacent structures, any mets, surgical margins, precursor lesions
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AIS: what are the histologic features?
- Cell crowding, loss of mucin, stratification, nucear enlargement, elongation and atypia, increased itoses and apoptotic debris
-
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How do you manage AGC on pap?
- Adenocarcinoma is less common than SCC, so this should be kept in Ddx
- AGC, proceed to colpo
- may be present along with a squamous intaepithelial lesion or have adenoca/AIS on cone or hysterectomy
118
How do you differentiate well-diff adenocarcinoma from endometrium and endocervix?
Endometrioid: background endometrial hyperplasia, squamous met, foamy macrophages in stroma, lack of SIL
Endocervical: markedly increased mitoses/apoptosis, elongated penicilate nuclei, background AIS/SIL, no endometrial hyperplasia
119
What are IHC markers to differentiate endometrial from endocervical adenocarcinoma?
Endocervical: p16+++, CEA+++, neg for ER/PR/vimentin
Endometrial: ER/PR/Vimentin +++, CEA neg to weak, p16 patchy
can also do HPV ish or do further ancillary testing
120
List 4 lesions in vulva with verruciform appearane
- Condyloma
- Seborrheic keratosis
- Verrucous carcinoma
- VIN/squamous cell carcinoma
121
Name some histologic variants of SCC vulva
- warty, basaloid, keratinizing, spindle cell, giant cell, verrucous
122
What is the ddx for SCC vulva
- pseudoepitheliomatous hyperplasia
- keratoacanthoma
- tangential secitoning, or adnexal involvement with VIN
123
Compare the 2 types of VIN
Usual VIN:
- HPV related, younger (35-50), precursor for basaloid, warty, less likely to go to SCC, p16 related. high recurrence.
Differentiated VIN:
- not HPV related, associated with LS. Postmenopausal. Precursor for keratinizing. p53+
124
Describe how you measure depth in VSCC and the managment implications of VIN/VSCC
- Depth is measured from DEJ of the adjacent dermal papilla to deepest point of invasion
- uVIN/dVIN: local excision
- SCC, 1A (size \<2cm, depth \<1mm) wide local witout total vulvectomy or LN sampling
\>1A: partial/total vulvectomy, LN sampling (sentinel or LN disection)
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