Molavi Chapter 17 - Uterus Flashcards

Atrophic endometrium from curettage
Low gland-to-stroma ratio with thin glands and almost cuboidal epithelium, no mitoses
Often come in strips that look like hairpins.

Proliferative endometrium curettage
Has a full, blue look to the stroma. The gland to stroma ratio should be 1:1.
Glands have pseudostratified columnar epithelium. Mitoses should be readily visible within the glands. (If this architecture is seen without mitoses, it is an inactive endometrium)

Secretory endometrium
Prominent spiral arterioles within a variably edematous stroma (such that in some places stromal cells look like nuclei floating in water).
Late-cycle stroma begins to get deidualized (pink cytoplasm) and lose their vacuoles.
Phases of endometrial change


Progestin-treated endometrium
Note the decidualized (pinkened) stroma and flattened gland epithelium. These changes are due to unopposed progesterone exposure.

Occurs at the end of the secretory phase (progesterone withdrawal)
The stroma takes on a blurry, blue hue and condenses into small aggregates. The surface epithelium shows eosinophilic metaplasia and becomes oncocytic in appearance. Fibrin thrombi in vessels and neutrophilic inflammation are common. Overylying epithelium is expanded into papillary tufts of pink cells.
acute endometritis
Endometritis
Diagnosis of acute endometritis requires microabscesses and epithelial destruction (since the presence of neutrophils aline may indicate normal menstrual breakdown).

Chronic endometritis
Diagnosed by the presence of plasma cells, which are not found in normal endometrium (unlike lymphocytes and macrophages).
Generally the stroma takes on a blue spindly look, there are increased numbers of lymphocytes. These low-power features should clue you in to go plasma cell hunting on high-power.

Disordered proliferative endometrium
This is a diagnosis used when there is some glandular crowding that falls short of a full diagnosis of hyperplasia
It is a mixture of cystically dilated, budding, and tubular glands in a prolfierative setting. Typically occurs during anovulatory cycles.
Classification of endometrial hyperplasia
- Simple vs complex
- Atypical vs non-atypical
- Note: Only the presence of atypia carries prognostic implications
Features of atypia in endometrial tissue
- More eosinophilic cytoplasm – as a result atypical glands appear paler on low power
- Round nuclei with pale, vesicular chromatin and prominent nucleoli
- Often occurs due to unexposed estrogen exposure

Atypical endometrial hyperplasia is alternatively called. . .
. . . endometrial intraepithelial neoplasia, or EIN
It is a precursor to endometrioid adenocarcinoma.
Early - Mid - Late secretory endomtrium
Early (days 16-18): Indicates ovulation has occurred. Dinstinct subnuclear vacuoles in endometrial glands.
Mid (days 19-23): Supranuclear-to-exhausted vacuoles, orderly row of nuclei, no mitoses. Significant stromal edema.
Late (days 24-28): Exhaused glands with a serrated profile, perateriolar cuffing with predecidua (stromal cells around arteries begin to have deciduous change, creating a pink halo around vessels).

Gestational endometrium
A solid sheet of decidua (plump, polygonal, lavendar cells with small oval nuclei). The glandular epithelium becomes papillary in nature with a hypersecretory appearance.
Arias-Stella reaction
Normal reaction of the endometrium to pregnancy
Well-formed glands with ballooning, cleared-out cytoplasm and very pleomorphic nuclei. Lack of mitoses or infiltration differentiates this from clear cell carcinoma (also clear cell usually occurs in postmenopausal patients).
An image is shown here demonstrating the bizarre histology that can be seen in these cases.

Placental site nodule

Prior region of placenta implantation
Characterized by the presence of intermediate trophoblastic cell aggregates within hyaline bodies.
Types of metaplasia that may be seen in the endometrium
- Tubal metaplasia: Luminal cilia
- Squamous metaplasia: Swirling islands of immature squamous cells with occasional keratinization
- Mucinous metaplasia: Mucinous, endocervical-type cells
- Eosinophilic metaplasia: Increased eosinophlic cytoplasm – can proliferate to the point of looking papillary, but nuclei remain bland.
Types of endometrial epithelial tumor
Endometrioid adenocarcinoma
Mucinous adenocarcinoma
Serous adenocarcinoma
Clear cell adenocarcinoma
Endometrioid carcinoma
- Most common type of endometrial cancer
- Occurs in postmenopausal women
- Precursor lesion is atypical endometrial hyperplasia (aka EIN)
- Associated with microsatellite instability
- In its well-differentiated form, it closely resembles atypical glands fused together without intervening stroma
- Overall architecture is cribriform or villoglandular

FIGO grading
- Grade 1: Tumor is <5% solid
- Grade 2: Tumor is 6-50% solid
- Grade 3: Tumor is >50% solid
- If there is significant nuclear atypia, the tumor gets upgraded from grade 1 to grade 2 or from grade 2 to grade 3.
Mucinous endometrial carcinoma
In order to qualify, >50% of cells must be mucinous
Like endometrioid they are primarily glandular but may have squamous differentiation.

Serous endometrial carcinoma
A separate tumor pathway from most endmoetrial cancers. These tumors are not hormone dependent, and not associated with endometrial hyperplasia.
It is considerably more aggressive than endometrioid carcinoma and tends to be diagnosed in older women. Assocaited with p53 mutations.
Histologically it resembles serous carcinoma of the ovaries. Its hallmark is papillary architecture though this is not required for diagnosis. The papillae have broad or fine fibrovascular cores with complex branching. Cells have large, prominent nucleoli, some of which are cherry red. Bizarre mitoses and multinucleated cells are often present.

Serous endometrial intraepithelial carcinoma (serous EIC)
Precursor lesion to serous endometrial carcinoma (although EIC itself also has metastatic potential, much like STIC).
A transofmation of the surface epithelium, particularly within the polyps of older women.
Often associated with a p53 mutation. Immunostain for p53 is used to confirm the diagnosis.
Histologically, characterized by an abrupt transition on the surface from benign epithelium to enlarged, pleomorphic, atypical, and mitotically active cells. Nuclear features are those of serous carcinoma (large cherry-red nucleolus, weird mitoses, multinucleation).

p53 stains in serous endometrial carcinoma
May be diffusely positive OR dead negative
Both suggest p53 mutations
Clear cell endometrial carcinoma
Like serous carcinoma, occurs primarily in older women and is unrelated to hormone levels. Prognosis is poor – it is almost always malignant.
NOTE: Clear cytoplasm can also occur in endometrioid carcinomas, so clear cytoplasm does not a clear cell carcinoma make.
Cytoplasm is glycogen-rich and clear, but cell borders are distinct. Architecture can be tubular, papillary, or solid. Significant nuclear atypia must be present.

Endometrial stromal nodule
Benign endometrial stromal tumor
Characterized by a well-circumscribed nodule of stroma without glands. Non-infiltrative by definition (if it is then it is LGESS).

Low-grade endometrial stromal sarcoma
Looks very similar to an endometrial stromal nodule, but demonstrates infiltration.
Minimal atypia and few mitoses, but have a prominent plexiform vascular proliferation (spiral arteries gone wild)

High-grade endometrial stromal sarcoma
Somewhat monotonous, round cell neoplasm with a defining translocation at t(10;17)(q22;p13)

Undifferentiated uterine sarcoma
Catchall category for high-grade sarcomas of the uterus with significant nuclear pleomorphism
Distingusihing this from a leiomyosarcoma or carcinosarcoma requires immunostains.
Malignant Mullerian mixed tumor
A form of carcinosarcoma – a biphasic tumor consisting of malignant glands in a sarcomatous stroma.
Often appears as a recognizable carcinoma (usually serous type), but with an adjacent sarcoma (large pleomorphic nuclei without distinct cell membranes) in the stroma. Other soft tissue elements like cartilage or skeletal muscle may also be in the mix.

Carcinosarcoma vs adenoscarcoma
Carcinosarcoma: Malignant epithelial neoplasm plus sarcoma
Adenosarcoma: Benign glandular epithelial neoplasm plus sarcoma
Uterine leiomyoma
You knew it was coming. The classic uterine fibroid.
A spindle-cell lesion with intersecting fascicles of elongated cells, typically intersecting at right angles. The nuclei are long and thin with fine pale chromatin and small nucleoli, ocassionally with a corkscrew nucleus (inset, characteristic of smooth muscle)
Stroma may be fibrotic, edematous, myxoid, or even hemorrhagic.

Uterine leiomyosarcoma
Presents as a large solitary mass – does not typically arise from preexisting leiomyomas. Resembles a fascicular leiomyoma, but there must be three differences:
- mitotic activity is high (over 10 per 10 HPF) [arrow]
- cytologic activity must be prominent. [circle]
- There must be some tumor necrosis present [not shown]
As with soft tissue sarcomas, atypia takes the form of large, dark nuclei with crisp, irregularly shaped nuclear borders, without nucleoli.

Adenomatoid tumor of the uterus
Benign proliferation of mesothelial origin. Occurs on the serosal surface of the uterus, resembling a leiomyoma both grossly and microscopically.
Mesothelial tumor cells induce muscle proliferation that is often mistaken for leiomyoma. However, there will be small clefted spaces in-between muscle fibers, lined by cuboidal cells forming gland-like or angiomatoid lumens.
Mistaking it for a fibroma is probably no harm to the patient, but mistaking it for metastatic adenocarcinoma is disastrous – unlike adenocarcinoma, adenomatoid tumors of the uterus stain positive for calretinin,
