SM_216b: Pathology of the Endometrium and Uterus Flashcards
Uterus consists of ____ and ____
Uterus consists of endometrium and myometrium
Describe myometrium histology
Myometrium histology
- Mostly smooth muscle (pink solid areas)
- Spindled cells arranged in fascicles at various angles to each other
- Fusiform, blunt-ended nuclei
Endometrium has two regions of mucosa: ____ and ____
Endometrium has two regions of mucosa
- Lower uterine segment / ishmus: not as responsive to hormones
- Uterine corpus: fully responsive to hormones
Two layers of endometrium in the corpus are ____ and ____
Two layers of endometrium in the corpus are basalis and functionalis
- Basalis: lower layer, does not cycle, regenerates endometrium after menses
- Functionalis: top layer, cycles and sheds at menses
Describe the proliferative endometrium
Proliferative endometrium
- Corresponds to ovarian follicular phase
- Response of endometrium to rising estrogen levels
- Glands are simple straight tubules
- Pseudostratified columnar cells
- Mitoses in glands and stromas
Describe the secretory endometrium
Secretory endometrium
- Corresponds to ovarian luteal phase
- Response of endometrium to progesterone (produced by corpus luteum)
- Variable appearance based on cycle day
Early secretory endometrium involves appearance of ____ and has a ____ appearance
Early secretory endometrium involves appearance of vacuoles (subnuclear then supranuclear) and has a piano keys appearance
Midsecretory endometrium involves ___
Midsecretory endometrium involves coiled glands
- Intraluminal secretions
- Stromal edema
- No more vacuoles
Late secretory endometrium involves ____ and ____
Late secretory endometrium involves spiral arterioles and stromal decidualization (large pink stromal cells)
- Sawthooth glands
- Neutrophils and other inflammatory cells
Menstrual endometrium is caused by a ___ and involves ___
Menstrual endometrium is caused by a drop in progesterone and involves a breakdown of glands and stroma
- No pregnancy -> corpus luteum involutes
- Fibrin, necrotic debris, hemorrhage, and inflammatory cells
Atrophic / inactive endometrium results from ___
Atrophic / inactive endometrium results from decreased estrogen levels (usually following menopause)
- Straight tubular glands
- Simple columnar to cuboidal epithelium
____ of endometrium cycles in response to hormones
Functionalis of endometrium cycles in response to hormones
____ phase of endometrium is characterized by vacuoles
Early secretory phase of endometrium is characterized by vacuoles
Non-neoplastic / functional endometrial disorders frequently cause ____
Non-neoplastic / functional endometrial disorders frequently cause anovulatory cycles, chronic endometritis, endometrial polyps, and adenomyosis
Anovulatory cycles appear as ____ on histology
Anovulatory cycles appear as proliferative glands with stromal breakdown on histology (no progesterone to cause secretory differentiation)
- Most frequent cause of dysfunctional uterine bleeding
- Due to hormonal imbalances, endocrine disorders, ovarian lesions, and generalized metabolic disturbances
Chronic endometritis appears as ____ and ____ on histology
Chronic endometritis appears as stromal change (spindling) and plasma cells
- Usually endometrium protected from infection by cervix
- Causes: PID, retained POC, IUD, TB, or other infection
- Acute endometritis is less common and due to infection
Endometrial polyps are ____ that appear as ____ on histology
Endometrial polyps are exophytic masses protruding into the endometrial cavity that appear as epihtelium on three sides with prominent blood vessels, fibrotic stroma, and dilated and irregularly shaped glands on histology
Adenomyosis is ___
Adenomyosis is endometrial glands and stroma within the myometrium
- Similar to endometriosis but confined to myometrium
- Can cause menometrorrhagia, dysmenorrhea, dyspareunia, and pelvic pain
Endometriosis appears as ___, ___, and ___ on histology
Endometriosis appears as endometrial glands, endometrial stroma, and evidence of hemorrhage on histology
- Ectopic endometrial tissue outside the uterus
- Most common sites of involvement: ovary, other pelvic sites, bowel
- Symptoms: infertility, dysmenorrhea, pelvic pain
- Can cause reactive fibrosis and adhesions between organs
- Usually in reproductive age women
Ovarian chocolate cyst and hemosidern-laden macrophages are ____
Ovarian chocolate cyst and hemosidern-laden macrophages are endometriosis
Describe theories of pathogenesis of endometriosis
Theories of pathogenesis of endometriosis
- Regurgitation theory: retrograde menstruation through tubes
- Benign metastasis theory: lymph-vascular spread
- Metaplastic theory: arises from metaplasia of peritoneum (mesothelium)
- Extrauterine stem / progenitor cell theory: stem cells from bone marrow
Top of the differential is ____
Top of the differential is chronic endometritis
Describe endometrial hyperplasia
Endometrial hyperplasia
- Precursor to most common type of endometrial carcinoma
- Increased gland-to-stroma ratio (glands > stroma)
- Associated with prolonged estrogen stimulation
- Inactivation of PTEN tumor suppressor gene in > 20% of hyperplasias
Endometrial hyperplasia classification involves ____ and ____
Endometrial hyperplasia classification involves
- Hyperplasia without atypia / benign hyperplasia
- Atypical hyperplasia / endometrial intraepithelial neoplasia
Describe endometrial hyperplasia without atypia
Endometrial hyperplasia without atypia
- Glandular crowding of varying degrees
- Glands are irregular in size and shape, sometimes cystic
- Glands can be back-to-back but still some intervening stroma
- No nuclear atypia (nuclei similar to normal glands)
- 1-3% progress to carcinoma
Describe atypical endometrial hyperplasia
Atypical endometrial hyperplasia
- Glandular crowding and irregularity
- Nuclear atypia: appear different from those in normal glands
- 23-48% have carcinoma at hysterectomy
- Treatment: hysterectomy or progesterone therapy (sometimes with eventual hysterectomy after pregnancy)
Endometrial carcinoma presents with ____
Endometrial carcinoma presents with abnormal bleeding
- 7% of all invasive cancer in women
- Diagnosis requires biopsy or curettage and subsequent histologic exam
- Type I and II
Compare type I and type II endometrial carcinoma
Type I and type II endometrial carcinoma
Type I endometrial carcinoma is ____ that resembles ____
Type I endometrial carcinoma is an exophytic or endophytic mass with or without myometrial invasion that resembles proliferative endometrium
- FIGO grade 1: mostly glandular, very little solid growth
- FIGO grade 2: some solid growth (glands > solid)
- FIGO grade 3: mostly solid growth
- Squamous metaplasia common
This is ____
This is endometrial carcinoma
- Complex, fused glands replacing normal endometrium
- Superficial invasion into myometrium
Fused glands with no stroma in between (cribriforming): swiss cheese appearance
Endometrial carcinoma that is mostly glandular growth (no solid growth) is ___
Endometrial carcinoma that is mostly glandular growth (no solid growth) is FIGO 1
Endometrial carcinoma that is a solid non-squamous growth is ____
Endometrial carcinoma that is a solid non-squamous growth is FIGO grade 2 or 3
____ is most common molecular alteration in type I endometrial carcinoma
PTEN mutation is most common molecular alteration in type I endometrial carcinoma
- Cowden syndrome: germline PTEN mutation, prediposed to endometrial carcinoma
- PIK3CA, KRAS, ARID1-alpha are also frequently mutation
- Microsatellite instability (defects in mismatch repair proteins): Lynch syndrome (HNPCC) if germline
- Poorly differentiated (FIGO grade 3) can have p53 mutations
____ in the most common type II endometrial carcinoma and almost always has ____ mutations
Serous carcinoma in the most common type II endometrial carcinoma and almost always has p53 mutations
- High-grade tumors by definition
- Background atrophic endometrium
- Often present with deep invasion and at higher stage
- Tumor cells can detach, travel through fallopian tubes, and implant on peritoneal surfaces
Describe uterine serous carcinoma (type II endometrial carcinoma) on histology
Uterine serous carcinoma (type II endometrial carcinoma) on histology
- Papillary or glandular growth pattern
- Marked nuclear atypia: high nuclear-cytoplasmic ratio, large darkly stained nuclei, prominent nucleoli, numerous and atypical mitoses
Carcinosarcoma (type II endometrial carcinoma) is composed of ____ and ____
Carcinosarcoma (type II endometrial carcinoma) is composed of
- Carcinoma: high-grade, often serous
- Sarcoma: homologous (smooth muscle, endometrial stroma) or heterologous (cartilage, skeletal muscle, bone)
Also called malignant mixed Mullerian tumor
Shared mutations in both components: most likely carcinomas with sarcomatous transformation
Large polypoid tumors
Carcinosarcoma histology involves ____ and ____
Carcinosarcoma histology involves malignant gland (carcinoma) and malignant stroma (sarcoma)
Endometrial carcinoma treatment usually involves ___
Endometrial carcinoma treatment usually involves hysterectomy ± radiation and/or chemotherapy
This is ____
This is endometrioid carcinoma
Describe mesenchymal tumors
Mesenchymal tumors
- Endometrial stroma -> endometrial stromal tumors (benign or sarcoma)
- Smooth muscle (myometrium) -> smooth muscle tumors (leiomyoma, leiomyosarcoma)
Describe endometrial stromal nodules
Endometrial stromal nodules
- Benign neoplasm
- Well-circumscribed
- Tumor cells resemble normal endometrial stroma
- JAZF1:JJAZ1 fusion due to chromosomal translocation t(7;17)(p15;q21)
Describe endometrial stromal tumors
Endometrial stromal sarcoma
- Infiltrative growth
- Low-grade (most common): tumor cells resemble normal endometrial stroma, JAZF1:JJAZ1 fusion due to chromosomal translocation t(7;17)(p15;q21)
Endometrial stroma sarcoma commonly involves ____ and ____ may occur
Endometrial stroma sarcoma commonly involves recurrence and late distant metastasis may occur
Describe leiomyoma
Leiomyoma (fibroid)
- Benign smooth muscle tumors
- Frequently multiply
- May be asymptomatic
- May cause abnormal bleeding, urinary frequency, pelvic pain, and infertility
- Common genetic abnormalities: rearrangements of 12q or 6p, MED12 mutations
- Trransformation to malignancy is rare
Describe appearance of leiomyoma
Leiomyoma (fibroid)
- Well-circumscribed round nodules / masses
- Variable size: subcentimeter to massive tumors filling pelvis
- Firm / rubbery, tan / what, whorled cut surfaces
- Location: submucosal (under endometrium), intramural (within myometrial wall), subserosal (under serosa)
Leiomyoma appears as ____ and ____ on histology
Leiomyoma appears as well-circumscribed nodule within myometrium and smooth muscle bundles at various angles to each other on histology
___, ___, and ___ are examined to differentiate leiomyoma (benign) from leiomyosarcoma (malignant)
Mitotic activity, tumor necrosis, and atypia are examined to differentiate leiomyoma (benign) from leiomyosarcoma (malignant)
- ≥2 of 3 following features means leiomyosarcoma: ≥ 10 mitotic figures / 10 HPF, tumor necrosis present, moderate to severe atypia
Describe leiomyosarcoma
Leiomyosarcoma
- Invasive endophytic tumor or polypoid exophytic tumor
- Most common in ages 40-60 but wide age range
- Genetics: complex, variable karyotypes
Leiomyosarcoma often ___, ___, and have ___ survival
Leiomyosarcoma often recur, can metastasize hematogenously, and have low survival
This is ___
This is leiomyoma
