Uterine Pathology 4

Question 1

What are the clinical features and pathological findings of adenomyosis?

Answer 1

• Clinical features
  
  • 20% of all uteri, usual minor
  • pain; bleeding; infertility
  • one of major reasons for hysterectomy
• Pathology
  
  • endometrial tissue in myometrium
  • 2mm deep into myometrium
  • adenomyoma: a mass lesion commonly seen in posterior myometrium
  • can harbor or develop endometrial hypoplasia and endometrial carcinoma
  • can coexist with fibroids

Question 2

What are the major histological features of adenomyosis?

Answer 2

• Cross section - diffusely thickened, trabecular and cystic structures, some of which appear black, representing blood
  
  • endometrial tissue in the myometrium may also cycle, causing abdominal pain.
• Microscopic features - presence of normal appearing endometrial tissue (both glands and stroma)
  
  • present in superficial or deep myometrium with hormonal effects similar to eutopic endometrium.

Question 3

What are the clinical findings, etiology, and pathophysiology of endometriosis?

Answer 3

• Clinic features:
  
  • incidence: Very common, affecting an estimated 2% to 8% of reproductive aged women and 30% of women with infertility
  • location: Ovary, uterine ligaments, rectovaginal septum, pelvic peritoneum, laparotomy scars, umbilicus, vagina, vulva, and appendix
  • symptoms: Pain; bleeding (“catamenial”); mass; bowel obstruction (adhesion)
  • risk for ovarian cancer
• Etiology: proposed causes of the disease
  
  • dissemination via retrograde flow or “metastases”
  • metaplasia of coelomic epithelium
  • lymphatic/hematogenous spread
• Pathophysiology
  
  • endometrial tissue outside of the uterus
    
    • cycle changes
    • no outlet: develop endometriosis, endometrioma, endometriotic cyst
    • inflammation, hyperplasia and carcinoma

Question 4

What are the major histological findings of endometriosis?

Answer 4

• Always functional and respond to hormonal change
• Chocolate cyst
  
  • ​blood-filled cyst, thick and dark
  • most commonly ovarian endometriotic cysts
  • frequently painful and fixed from inflammation
  • fibrotic tissue eventually replaces endometrial tissue
  • size may vary from 10 cm in diameter
• Histology
  
  • ​endometrial glands and stroma (1)
  • hemosiderin deposition (2)
  • fibrosis (3)

Question 5

What are the two histologic types of endometrial polyps? What is the pathophysiology?

Answer 5

• Two histologic types
  
  • functional type (endometrium in same phase as non-polypoid endometrium)
  • non-functional type
• Pathophysiology
  
  • common in patients on Tamoxifen.
  • common for uterine bleeding and endometritis
  • risk for hyperplasia and EMC
• Neoplastic component:
  
  • stroma
  • associated with chromosome 12q15 alteration

Question 6

What are the major histological features of endometrial polyps?

Answer 6

• Increased glands with varied size and shape (loss of polarity)
• Stromal fibrosis (pink stroma)
• Prominent thick-walled blood vessels

Question 7

What are the subtypes of endometrial adenocarcinoma and what types of lesions and genetic alterations are common to each type?

Answer 7

• Endometrioid type (80%)
  
  • peak incidence 55-65 yrs.
  • precancer lesions: hyperplasia, endometrial intraepithelial neoplasia (EIN)
  • common genetic alterations:
    
    • estrogen driving stepwise progression
    • Lynch syndrome (microsatellite instability/DNA repair defects): 10%
    • PTEN mutations >50%
    • ARID1A and PIK3CA mutations (30%)
    • β-catenin mutations
• Non-endometrioid (aggressive) type (20%)
  
  • older-aged females (>60 yrs)
  • precancer lesions: endometrial intraepithelial carcinoma (EIC)
  • common genetic alterations:
    
    • p53 mutations

Question 8

What is endometrial intraepithelial neoplasia (EIN)?

Answer 8

• Localized lesion with objective histologic criteria
• Characterized by monoclonal growth of mutated cells
• Associated with a 45-fold elevated cancer risk

Question 9

What is endometrial intrapepithelial carcinoma (EIC)?

Answer 9

• Endometrial carcinoma precursor
• Localized lesion characterized by replacement of endometrial surface epithelium or glands by fully malignant cells
  
  • resembles high-grade invasive serous carcinoma
  • characteristic features is p53 mutations

Question 10

What are some major risk factors that predispose to endometrioid adenocarcinoma?

Answer 10

• Unopposed estrogen
• Obesity (increased estrogen)
• Anovulation (decreased progesterone)
• Diabetes
• Tamoxifen use
• Early menarche/late menopause
• Genetics = lynch syndrome

Question 11

What gene is an important factor in the development of endometrial hyperplasia and endometrioid carcinoma?

Answer 11

• PTEN - loss may activate estrogen-driven molecular pathways
  
  • activated AKT-mediated
  • estrogen signaling cross talk
  • PTEN mutations can be detected in early (EIN) and invasive carcinoma
• Lynch Syndrome
  
  • microsatelite instabilitiy/DNA repair defects

Question 12

Compare and contrast endometrial adenocarcinoma types I and II in terms of:

Age

Hyperestrogenic

Hyperplasia

Grade

Myometrial invasion

Histology

Behavior

Genetic alterations

Answer 12

• Type I
  
  • age - premenopausal
  • hyperestrogenic
  • hyperplasia present
  • low grade
  • myometrial invasion - less often and superficial
  • histology - endometrioid
  • behavior - stable
  • genetic alterations - microsatellite instability, PTEN, beta-catenin, and K-RAS
• Type II​
  
  • age - postmenopausal
  • not hyperestrogenic
  • hyperplasia absent
  • high grade
  • myometrial invasion - deep
  • histology - serous, clear cell
  • behavior - progressive
  • genetic alterations - p53 mutations, E cadherin alterations, Her2/neu

Question 13

What are the histological features and grading of Type I endometrial adenocarcinoma?

Answer 13

• Endometrioid type
• Histology:
  
  • glands with pseudostratified and ‘pencil-thin’ nuclei
  • back-to-back or ‘Cribriform’ gland formation
  • mostly show low grade nuclear atypia
• FIGO grade by architecture:
  
  • Grade I:
  • Grade II: 5-50% solid growth
  • Grade III: >50% solid growth

Question 14

What is the clinical significance and pathogenic diagnosis of Type II endometrial adenocarcinoma?

Answer 14

• Serous type
• Clinical significance
  
  • high propensity for lymphovascular invasion and extra-abdominal spread (approximately 40 - 70 % disease beyond the uterus)
  • 50% of stage III or IV disease and nearly 40% of all deaths while only comprising 10% of cases
  • aggressive surgical procedures:
    
    • a total abdominal hysterectomy
    • bilateral salpingo-oophorectomy (TAH-BSO)
    • pelvic/paraaortic lymph node dissection,
    • omentectomy,
    • assessment of the peritoneal cavity including pelvic and diaPathologic diagnosisphragmatic cytology
• • typical histologic features
    
    • distinct tumorigenesis
    • unique immunohistocheical profile

Question 15

What are the histological findings of Type II endometrial adenocarcinoma?

Answer 15

• Strongly immunoreactive for p53
• Papillary architecture
• Large and pleomorphic nuclei
• High nuclear cytoplasmic ratio
• Prominent nucleoli
• Hobnail
• Frequent lymphovascular invasion

Question 16

Differentiate between the grading and staging of endometrial carcinomas.

Answer 16

• Grading for endometrioid carcinoma (use FIGO system)
  
  • G1. Well-differentiated adenocarcinoma
  • G2. Differentiated adenocarcinoma with partly solid (less than 50% but more than 5%) areas
  • G3. Predominantly solid or entirely undifferentiated carcinoma (>50%).
• For Serous and clear cell carcinomas and carcinosarcoma
  
  • automatically classified as grade 3
• Staging for endometrial carcinoma
  
  • Stage I. Carcinoma is confined to the corpus uteri itself.
  • Stage II. Carcinoma has involved the corpus and the cervix.
  • Stage III. Carcinoma has extended outside the uterus but not outside the true pelvis.
  • Stage IV. Carcinoma has extended outside the true pelvis or has obviously involved the mucosa of the bladder or the rectum.

Question 17

What are endometrial biphasic tumors?

Answer 17

• Definition
  
  • consists of both epithelial and mesenchymal component
• Carcinosarcoma (malignant mixed mullerian tumor)
  
  • both epithelial and stromal cells are malignant
• Adenosarcoma
  
  • epithelia benign, stroma malignant

Question 18

What are leiomyomas? What are the symptoms and genetic information?

Answer 18

• Generally benign
• Most common pelvic tumor of reproductive-aged women;
  
  • 60-70% by age of 50years old
  • blacks>whites;
  • often multiple
• Symptoms include, Submucosal: bleeding/menorrhagia
  
  • intramural and subserosal: pain, infertility, urinary incontinence/constipation
• Genetic information
  
  • 40% fibroids gain chromosomal abnormalities: t(12;14), del(7q)…
  • MED12 mutations seen in 60-70% fibroids

Question 19

What are the histologic findings for leiomyomas (fibroids)?

Answer 19

• Intersecting fascicles/ storiform/ whorled
• Bland spindle cell proliferation
• Brightly eosinophilic cytoplasm
• Hyalinization/thick collagen bundles
• No significant cytologic atypia

Question 20

What are leiomyosarcomas? What is the clinical presentation?

Answer 20

• Malignant, metastases common
• Clinical presentation
  
  • most common pure uterine sarcoma
  • peak incidence 40-60 yrs
  • 50% blood-borne metastasis
  • 5-yr. survival: 40%
• Tumorigenesis
  
  • mostly de novo
  • gain complex genomic alterations
  • frequent p53 mutations
• Can recur or have metastatic disease years after initial treatment

Question 21

What are the gross and histological features of leiomyosarcomas?

Answer 21

• Gross:
  
  • presentsas a large, solitary, fleshy mass with infiltrating boarder and metastasis
• Histological features:
  
  • moderate to sever nuclei atypia
  • frequent mitosis
  • tumor necrosis

Question 22

Describe the pathology diagnosis algorism and the differential diagnosis of uterine leiomyosarcoma.

Answer 22

• Pathology diagnosis algorism
  
  • infiltrating and invasive growth patterns
  • presence of tumor Necrosis
  • severe Cytological atypia
  • mitotic count more than 10 /10 high power field
• Differential diagnosis
  
  • atypical uterine smooth muscle tumors
  • uterine sarcoma
  • immunostainsoften needed in assistance for definite diagnosis
    
    • smooth muscle marker
    • P16, p53, ER, PR

Question 23

What is the clinical presentation, histology, and genetics of a partial mole? Is there a risk for gestational trophoablastic tumors?

Answer 23

• Clinical presentation
  
  • normal size with fetus
  • missed abortion
  • some hydropic
• Histology
  
  • large irregular villi
  • areas of trophoblastic proliferation
  • stromal edema
• Genetics:
  
  • molecular analysis: triploid (p:m=2:1)
  • immunostain for p57: positive
• Risk for gestational trophoblastic tumors is low

Question 24

What is the clinical presentation, histology, and lab tests for a complete mole? What is the risk for gestational trophoblastic tumors?

Answer 24

• Clinical:
  
  • ‘snowstorm’,
  • bleeding,
  • un-proprotional larger uterus
• Histology
  
  • large and edematous villi and stromal cell necrosis
  • trophoblast proliferation
  • no fetus
• Lab tests:
  
  • karyotype: 46, XX
  • immunostain for p57: negative (why?)
• Risk for gestational trophoblastic tumors: high
  
  • invasive mole
  • choriocarcinoma