Histopathology of the Uterus II - Polyps, Hyperplasia and Tumors

omarys's version from 2017-05-18 23:12

Section 1

Question Answer
FOCAL hyperplasia of endometrial tissue, highly vascular and has significant connective tissueEndometrial polyp
Are polyps related to cancer of the uterus?Nope, they're completely benign
Clinical manifestations of endometrial polypsAbnormal bleeding (but can be asymptomatic)
Most common cause of abnormal bleedingPolyps (in uterus or cervix)
T or F- Polyps are responsive to both estrogen and progesteroneFalse. They respond to estrogen but not to progesterone.Hint: This is a strange/counter-intuitive fact about polyps
Tamoxifen, an ER antagonist and anti-breast cancer tx, is a ___ factor for the development of endometrial polyps. (risk or protective?)RISK! Despite being an anti-estrogen in the breast, it has a pro-estrogen effect in the uterus, leading to development of polyps.Counter-intuitive fact #2 about polyps (or tamoxifen, whatever)

Section 2

Question Answer
High levels of estrogen unbalanced by progesterone can lead tohyperplasia (of endometrial tissue)
What drugs can create the effect of high levels of estrogen unbalanced by progesterone?Fertility tx
What metabolic conditions can create the effect of high levels of estrogen unbalanced by progesterone?Metabolic syndrome/obesity (peripheral production of estrogen in excess)
What lesions can create the effect of high levels of estrogen unbalanced by progesterone?Tumors (e.g. granulosa cell tumor)Recall that granulosa cell tumors are part of the sex cord-gonadal stromal tumors (i.e. they belong to the non-epithelial group of ovarian tumors)
What is the molecular change/basis underlying the development of hyperplasia (and carcinoma too)?PTEN (tumor suppressor) mutations
The P in PTEN stands forphosphatase (the protein that the gene encode DEphosphorylates PIP3)PIP3 is the active form and leads to a proliferation signal. The phosphatase turns it into PIP2 which is inactive. When the phosphatase is deficient (due to the mutation), PIP3 is dominant and causes excessive proliferation signals.

Section 3

Question Answer Column 3
Cowden syndrome =germline mutation in PTEN, leading to (mostly) hamartomas and (sometimes) carcinomas in various locations (thyroid, breast, GIT, and endometrium)Mnemonic: PTEN and Cowden sound alike. PTEN = petit = small, which means Cowden is the bigger one. So Cowden is PTEN on steroids: there's a germline mutation in PTEN and the ensuing tumors are all over the place.
When classifying hyperplasias, 2 criteria are evaluated:cytology (which determines atypia) + architectureRecall similar classification in endometriosis
In hyperplasia, "simple" and "complex" relate tothe overall architecture of the tissue, if complex- glands are very dense and irregular
In hyperplasia, "typical" and "atypical" relate tohow individual cells look, if atypical- the nuclei are hyperchromatic and more round
Of the 4 different classifications of hyperplasia, which is considered rare?Simple atypical hyperplasia
Which comes before, complex typical HP or complex atypical HP?Complex typical HP (the "milder" one) occurs first
Complex typical HP >> Complex atypical HP >> ?Adenocarcinoma

Section 4

Question Answer
4 major categories of uterine tumors (based on tissue of origin)endometrial gland tumors (=epithelial) ; endometrial stromal tumors (=mesenchymal) ; mixed tumors (=both epi' and mes') ; myometrial tumors
Type I gland tumors include (2)endometrioid, mucinous (both are carcinomas)
Type II gland tumors include (3)serous, clear cell, mixed mullerian (all carcinomas)
Stromal tumors include (2)stromal nodule (benign), low-grade sarcoma and high-grade/undifferentiated sarcoma
Mixed tumors include (1)Carcinosarcoma
Myometrial tumors include (2)leiomyoma, leiomyosarcoma

Section 5

Question Answer
Low-grade endometrial sarcoma is AKAendolymphatic stromal myosis (bc it likes invading lymph and blood vessels)
Despite being malignant, low-grade endometrial sarcoma isindolent and cytologically "mild" (few mitoses, atypia, etc.)
Molecular basis of low-grade endometrial sarcoma?Translocation bwn chromosomes 7 and 17 >>> fusion of 2 genes >> production of "fusion protein"genes are JAZF1 and polycomb-group genes
High-grade/undifferentiated sarcoma lacks markers and characteristic of stromal tissue (i.e. it is negative in PR and ER stains)
Unlike high-grade sarcoma, low-grade endometrial sarcoma stains positive forPR, ER, CD10
What stain is HIGH-grade sarcoma positive for?Cyclin D1Makes sense because cyclin D1 is a protein required for progression through the G1 phase of the cell cycle

Section 6

Question Answer
What do myometrial and stromal tumors have in common?Both are of mesenchymal origin
Leiomyoma is AKAfibroid
T or F- Estrogen has no effect on the myometrium.False. Like the endometrium, the myometrium is affected by estrogen and muscle cells in it proliferate in response to the hormone (this is why leiomyomas are common in fertile women)
Clinical manifestations of leiomyomas?Can affect pregnancy/fertility, e.g. if the tumor is near the cervix then a C-section might be necessary
Which variant of leiomyoma causes endometrial atrophy?submucosal
T or F- Weird looking nuclei or multinucleated cells necessarily mean the tumor is leiomyosarcoma (malignant).False! One variant of leiomyoma is called "bizzare/symplastic leiomyoma" and it fits the description, although benign.
T or F- Leiomyomas can spread/send metastases to lymph nodes/elsewhere.True- this is not "proper" metastasis though, so it's still benign.
(sigh) T or F- Leiomyomas can disseminate into the peritoneum, where small lumps of tumors can be found.True. This is still not metastatic spread.
Leiomyoma's mottoSIKE! im not malignant bro. also I have identity issues..
Can leiomyoma develop into leiomyosarcoma?NO. Just no.

Section 7

Question Answer
Unlike leiomyomas, leiomyosarcomas occur infertile as well as post-menopausal women
What tumor should be considered in the DD alongside leiomyosarcoma?"mitotically active leiomyoma" (recall Leo's identity issues)
In _________ necrosis the architecture of dead tissue is preserved for at least a couple of dayscoagulative
Coagulative necrosis usually results fromischemia/infarction
3 criteria must be met for the tumor to be classified as leiomyosarcoma:intense atypia, coagulative necrosis, 15 or more mitoses per 10HPF

Section 8

Question Answer
When both the mesenchymal and epithelial components of a mixed tumor are benign, the tumor can be:adenofibroma or adenomyoma
Which is more common, carcinofibroma or adenosarcoma?Adenosarcoma
Which is the most common mixed tumor?Carcinosarcoma (both components malignant)
Carcinosarcoma is AKAMMMT - malignant mixed mullerian tumor
Carcinosarcoma is considered a very poorly differentiated ____ tumor (epithelial or mesenchymal?)epithelial - it's an epithelial tumor so badly differentiated that parts of it started looking like mesenchyme
Carcinosarcoma will usually occur in post-menopausal women
Can carcinosarcoma cause bleeding into the uterus?Sure, it's 2x malignant and shit.
Can carcinosarcoma include bone or cartilage or skeletal muscle tissue?It's a double origin double malignant tumor. No one is safe.heterologous mesenchymal component
Compression of glandular structures by hypercellular stromal tissue is called ____ ______ and is characteristic of ________periglandular cuffing ; adenosarcoma
Adenosarcomas are usually low- or high-grade?low-grade
Adenosarcomas ___ (are/are not) affected by estrogen?They are. This is why oophorectomy works as a tx.
An effective tx for adenosarcomas isoophorectomy
Mutations involved in carcinosarcomaPTEN, P53, PIK3CA

Section 9

Question Answer Column 3
MSI (microsatellite instability) is associated with which carcinoma, type I or II?Type I. Also associated w/ type I: PTEN, KRASP53 and PIK3CA are associated with type I as well, but these two are also found in type II.
Precursor of type I adenocarcinoma?Hyperplasia (complex atypical)
Precursor of type II adenocarcinoma?endometrial intraepithelial carcinoma (EIC)
Endometrioid morphology characterizes which adenocarcinoma, I or II?Type I (the more indolent, milder type) - it looks similar to (normal) endometrial epithelium.
Clear cell and serous carcinomas belong to type I or II?Type II - shit got real.
Which type of adenocarcinoma is related to unopposed estrogen?Type Irecall that hyperplasia is affected by estrogen, and type I develops from hyperplasia, so it follows that the clinical setting is common
Can progesterone therapy be effective in type I adenocarcinoma?It's good for hyperplasia (including complex atypical), less for cancer. If the patient is a young woman and hysterectomy is not favorable, high-dose long-term progesterone tx may be given.
Type II adenocarcinoma affects women ____ (above/below?) age 65.Above. Type I affects 55-65 usually, while type II is more common in 65-75.
T or F- Type II adenocarcinoma is related to estrogen levels.False
While type I adenocarcinoma develops from a hyperplastic endometrium, type II develops from an ______ endometriumatrophic (recall age group)
3 subtypes/variants of type II adenocarcinoma:clear cell, serous (epithelium looks more fallopian than endometrial), mixed mullerian

Section 10

Question Answer
MLH1 is a ____ ______ ____ geneDNA mismatch repair
HNPCC/Lynch is characterized by ______ _____ due to mutations in _____microsatellite instability ; MLH1
The 2 most common cancers associated with HNPCC: ____ cancer and endometrial cancercolon
Type I endometrial adenocarcinoma is a multi-step process usually starting with a ____ mutationPTEN (leads to hyperplasia)
The second step in type I carcinogenesis is a ____ mutation MLH1 (simple hyperplasia >> complex hyperplasia)
HNPCC is related to the development of which type of adenocarcinoma, clear cell or endometrioid?Endometrioid (type I)
In the FIGO grading system, the more solid the tumor, the ____ the grade and the ____ the differentiationhigher ; poorer
A FIGO G1 tumor is well differentiated - less than 5% 'solidity'
A FIGO G3 tumor ispoorly differentiated - more than 50% of tumor is solid massNote: FIGO grading can also take into account the cytology of the tumor- i.e. if the tumor isn't very solid, but its cells are extremely atypical/mitotically active then the grade would be G3. Examples: clear cell, serous.

Section 11

Question Answer Column 3
IHC for the proteins of which genes can help differentiate bwn type I and type II?PTEN, MLH1, beta-catenin, KRAS, ER, E-cadherin (all + for type I)some of these might be positive in type II as well, but they're a lot more common in type I. Also consider grade of type I- if it's high, the tumor will be more similar to type II tumors, so e.g. P53 won't make a difference.
IHC for E-cadherin is positive in type I or II?Type I