What is the result of hormones on endometrium?
Estrogen: Growth of endometrium
Progesterone: Preparation of endometrium for implantation
Remove progesterone and shedding occurs
What is Asherman Syndrome?
Secondary amenorrhea due to loss of basalis (regenerative layer of endometrium) and scarring
- Results from overaggressive dilation and curettage
What is anovulatory cycle?
Lack of ovulation
- Results in estrogen-driven proliferative phase without progesterone-driven secretory phase
- Common cause of dysfunction uterine bleeding, especially during menarche and menopause
What is acute endometritis? Common causes?
Bacterial infection of endometrium
- Presents as:
Abnormal Uterine Bleeding
- Usually due to retained products of conception
What is chronic endometritis?
Chronic inflammation of endometrium
- Characterized by plasma cells
- Common causes include:
retained products of conception
TB (would also see granulomas)
- Presents with:
Abnormal uterine bleeding
What is an endometrial polyp?
Hyperplastic protrusion of endometrium
- Presents as abnormal uterine bleeding
- can arise as side effect of tamoxifen
What is endometriosis?
Endometrial glands AND stroma outside the uterine endometrial lining
- Presents with dysmenorrhea and pelvic pain; may cause infertility
What are the current theories on how endometriosis develops?
1. Retrograde Theory: products of menstruation go backward through uterus out the fallopian tubes into the abdominal cavity (prevailing theory)
2. Metaplastic Theory: Endometrial metaplasia is cause of endometriosis
3. Lymphatic Dissemination theory: endometrium spreads into lymphatics and into the rest of the body
What are the most common sites of endometriosis involvement?
Ovary - Chocolate cysts
Uterine ligaments - pelvic pain
Pouch of Douglas - pain with defecation
Bladder wall - pain with urination
Bowel serosa - abdominal pain and adhesions
Fallopian tube mucosa - scarring --> infertility and ectopic pregnancy
What is adenomyosis?
Presence of endometriosis in the uterine myometrium
Where does endometriosis have an increased risk of carcinoma?
At the site of endometriosis
- Especially when the ovary is involved
What is endometrial hyperplasia? What drives this process?
Hyperplasia of endometrial glands relative to stroma
- Consequence of unopposed estrogen
- Presents as postmenopausal (no longer has a progesterone phase) uterine bleeding
How is endometrial hyperplasia classified?
Based on architectural growth and cellular atypia
- Most important predictor for progession to carcinoma is cellular atypia
What is the clinical presentation of endometrial carcinoma?
Malignant proliferation of endometrial glands
- Presents as postmenopausal bleeding
- arises via two distinct pathways: hyperplasia due to unopposed estrogen (endometrioid) and sporadic production of cancer from atrophic endometrium (serous with papillary structures)
What ages area associated with endometrial cancer?
Sporadic pathway: woman >70yrs old
Hyperplastic pathway: woman ~50-60yrs old
What are characteristics of the hyperplastic pathway of endometrial carcinoma?
Carcinioma arises from endometrial hyperplasia
- Risk factors are related to estrogen exposure (unopposed estrogen leads to endometrial hyperplasia)
- Average age is 60yrs old
- Histology is endometrioid
What are characteristics of the sporadic pathway of endometrial carcinoma?
Carcinoma arises in atrophic endometrium
- No evident precursor lesion
- Average age is 70yrs old
- Histology is usually serous and papillary
Psammomma bodies may be evident
- Driven by p53 mutations
- Very aggressive behavior
Where are psammoma bodies seen?
Papillary serous carcinoma of the endometrium
Papillary carcinoma of Thyroid
What is Leiomyoma?
Benign proliferation of smooth muscle arising from myometriium
- Related to estrogen exposure
- Multiple, well-defined white whorled masses
What are the symptoms of a leiomyoma?
Most common symptom: Asymptomatic
Any presentation otherwise is a derivative of the leiomyoma:
Stretching uterine lining = abnormal uterine bleeding
Block the ability of the ovum to implant = infertility
Pelvic mass detected
What are characteristics of leiomyosarcoma?
Malignant mesenchymal proliferation of smooth muscle arising from the myometrium
- Arises de novo (leiomyoma DOES NOT become leiomyosarcoma)
- Usually seen in postmenopausal women
- Single lesion with necrosis and hemorrhage
- Necrosis, mitotic activity, and cellular atypia
What are the three cell types of the ovary, where do they come from, and what type of tumor arises from them?
Surface epithelium: lines the surface of the ovar, derive surface epithelial tumors
Germ cells: from the oocyte, creates germ cell tumors
Sex cord stroma: from granuloma, theca, and fibroblast cells that support the oocyte, creates sex cord stromal tumor
What are surface epithelial tumors? What are the two most common subtypes?
Most common type of ovarian tumor
- Derived from coelomic epithelium that lines the ovary
- Two most common subtypes of surface epithelial tumors are serous and mucinous (both usually cystic)
What is a cystadenoma?
Benign tumor composed of single cyst with simple, flat lining
- Most common in premenopausal women (30-40)
(can be serous or mucinous, depending on epithelium)
What is a cystadenocarcinoma?
Malignant, epithelial tumor composed of complex cysts with thick, shaggy lining
--> clear invasion of cells into the connective tissue
- Most commonly arises in post menopausal women (60-70yrs old)
- Can be serous or mucinous, depending on epithelium
What are borderline tumors?
Tumors with features between benign and malignant
--> better prognosis than clearly malignant tumors, but still carry metastatic potential
What does BRCA1 mutation increase risk for?
Increased risk of breast cancer as well as serous carcinoma of the ovary and fallopian tube
What are the four types of surface epithelial ovarian tumors?
Serous - can be benign, borderline, or malignant
Mucinoid - can be benign, borderline, or malignant
Endometrioid - usually malignant
What are characteristics of endometrioid tumors?
- Usually malignant, surface epithelial tumor of the ovary that resembles endometrium
- May be associated with endometriosis
- 15% of patients have separate endometrioid carcinoma in uterus
What type of cells make up a Brenner tumor?
Usually contains urothelium
What is the presentation of surface epithelial tumors?
Present late, leading to poor prognosis
- Vague abdominal symptoms; pain, fullness
- Epithelial carcinomas tend to spread locally, especially to peritoneum
- Useful serum marker to monitor treatment: CA-125
What are characteristics of Germ cell tumors?
2nd most common ovarian tumor
- Usually occur in women of reproductive age
- Subtypes mimic tissues normally produced by germ cells
What ovarian tumor would I suspect for a woman of:
15-30 yrs old: Germ cell tumor
35-40 yrs old: Benign surface epithelial tumor
60-70 yrs old: Malignant surface epithelial cell tumor
What are the types of germ cell tumors?
- Cystic teratoma
- Embryonal Carcinoma
- Yolk Sac Tumor
- Dysgerminoma (mass of germ cells)
What is a cycstic teratoma?
Benign, cystic tumor composed of fetal tissue derived from two or three embryological layers
- Most common germ cell tumor in females
- bilateral in 10% of cases
What could lead to a potential malignancy with a cystic teratoma?
Presence of immature tissue (most commonly neural ectoderm) or somatic malignancy in the mature tissue of the teratoma
What is the most common somatic malignancy of teratomas?
Sqamous cell carcinoma of the epithelium in the teratoma
What is struma ovarii?
Cystic teratoma composed primarily of thyroid tissue
- Can lead to hyperthyroidism because teratoma has hyperfunctioning thyroid tissue
What is Dysgerminoma?
Compoosed of large cells with clear cytoplasm and central nuclei (look like an oocyte/germ cell)
- Most common malignant germ cell tumor
- Testicular counterpart is seminoma
- Good prognosis, responds to radiotherapy
- Serum LDH may be elevated
What is an endodermal sinus tumor?
Malignant tumor that mimics yolk sac
- Most common germ cell tumor in children
- Serum AFP is often elevated
- Schiller-duval bodies are seen in histology (same as testicular yolk sac tumors)
What is choriocarcinoma?
Malignant proliiferation of placental-like tissue
- Composed of trophoblasts (syncytiotrophoblasts and cytotrophoblasts) --> villi are absent
- Small, hemorrhagic tumor with early hematogneous spread (due to syncytiotrophoblasts ability to infiltrate vasculature)
- High ß-HCG
- Poor response to chemotherapy
What is an embryonal carcinoma?
Composed of large, primitive cells
- Aggressive with early metastasis
What are characteristics of granulosa-theca cell tumor?
Neoplasm of granulosa and theca cells
- often produces estrogen
- presents with signs of estrogen excess (symptoms vary with age)
What is a sertoli-leydig cell tumor?
Tumor that mimics sex cord-stromal cells of testicle
- Sertoli cells form tubules
- Leydig cells contain characteristic Reinke crystals
- May produce androgen; associated with hirsutism or virilization
What are characteristics of fibromas?
Benign tumor of fibroblasts
- Associated with pleural effusion and ascites (Meigs syndrome)
What is a Kruckenberg tumor?
Mucinous carcinoma from some site outside the ovary that metastasizes and spreads to both ovaries
- primary site can arise from:
gastric carcinoma (diffuse subtype with signet ring cells where mucus has displaced the nucleus)
breast tumor (lobular carcinoma - also has signet ring cells)
What is pseudomyxoma peritonei?
Classically known as "Jelly Belly"
- Primary source of tumor is usally a tumor in appendix which produces abundant mucus in peritoneum
How do you grossly determine if a mucinous tumor is primarily ovarian or kruckenberg?
Kruckenberg = bilateral
Surface epithelial mucinous tumor = unilateral