Ovaries Flashcards
What may patients present with that suggest ovarian causes?
- Asymptomatic
- Vaginal bleeding
- Infertility
- Hirsutism/virilization
- Pain
- Mass
- Increasing abdominal girth
- Weight loss or gain
- History of recurrence or other medical condition
- Systemic disease or syndrome
What are the most common lesions encountered in the ovary?
- Functional or benign cysts or tumors
Where do cystic follicles originate?
- Originate from unruptured Graafian follicles or in follicles that have ruptured and immediately sealed
What do cystic follicles look like?
- Usually multiple
- Range in size up to 2 cm
- Filled with clear serous fluid and are lined by a gray, glistening membrane
What is a follicle cyst?
- Cysts greater than 2cm can be felt on palpation or during ultrasound (follicle cyst)
- May cause pelvic pain
What is a luteal cyst?
- Present in normal ovaries of women of reproductive age
- Lined by a rim of bright yellow tissue containing luteinized granulosa cells and are prone to rupture (cause peritoneal reaction)
What is polycystic ovarian syndrome (PCOS)?
- Multiple cysts (cystic follicles that don’t mature) combined with:
- Hyperandrogenism
- Menstrual irregularities
- Chronic anovulation
- Decreased fertility
What is PCOS associated with?
- Obesity
- T2DM
- Premature atherosclerosis
- Increased free serum estrone (E1)
What is E1? What does it do?
- Estrone
- Menopausal estrogen produced by aromatization of androstenedione in peripheral fatty tissue
- Less potent than E2
What is E2? What does it do?
- Estradiol
- Predominates in reproductive years
- Most potent estrogen produced by aromatization of testosterone in Graafian follicle
What is E3? What does it do?
- Estriol
- Placental estrogen that originates in fetal adrenal gland and DHEA and converted in placenta
- Least potent
What are some symptoms of PCOS?
- Menstrual disorder/amenorrhea
- Infertility
- Hirsutism/male pattern baldness/acne
- Obesity/metabolic syndrome
- Diabetes
What ages are benign ovarian tumors seen in?
- Women 20-45
- 80% of ovarian tumors
What age are malignant ovarian tumors seen in?
- Women 45-65
How are benign ovarian tumors found?
- Unexpectedly on abdominal or pelvic exam
- Maybe during a different surgery
When do benign ovarian tumors start to produce symptoms?
- When they are large in size
What are the most common symptoms of ovarian tumors?
- Abdominal pain and distention
- Urinary and GI tract symptoms due to compression by the tumor or cancer invasion
- Vaginal bleeding
How are primary ovarian neoplasms grouped?
- Surface (müllerian) epithelium
- Germ cells
- Sex cord-stromal cells
What are some epithelial ovarian tumors?
- Serous
- Mucinous
- Endometrioid
- Clear cell
- Brenner
What are some germ cell ovarian tumors?
- Teratoma
- Dysgerminoma
- Yolk sac tumor
- Mixed GC tumors
What are some sex cord-stromal ovarian tumors?
- Granulosa tumors
- Fibromas/Thecomas
- Sertoli-Leydig cell tumors
- Hilus (leydig) cell tumor
- Gonadoblastoma
What are some metastatic (non ovarian) tumors?
- Appendiceal
- Gastric
- Breast
- Pancreaticobiliary
- Colonic
Where do most primary ovarian neoplasms of the ovary come from?
- Müllerian epithelium
What is the classification based off of for tumors?
- Differentiation and extent of proliferation of the epithelium
What are the three major histologic types of tumors based on differentiation of the neoplastic epithelium?
- Serous
- Mucinous
- Endometrioid
How are the epithelial proliferations classified?
- Benign
- Borderline
- Malignant
What are the subclassifications of benign tumors?
- Cystadenoma (includes cystic areas)
- Cystadenofibroma (has cystic and fibrous areas)
- Adenofibroma (predominantly fibrous areas
What are borderline and malignant tumors called when they have a cystic component?
- Cystadenocarcinoma
Which tumor has the highest incidence of being bilateral?
- Malignant
- Metastatic
What are some high risk features of malignant serous ovarian tumors?
- Women with low parity
- Inherited germline mutations of the BRCA1 and BRCA2 gene
What are some features that decrease risk of malignant serous ovarian tumors?
- Women 40-59 who have taken oral contraceptives or undergone tubal ligation
What does the biologic behavior of serous tumors depend on?
- Degree of differentiation and the distribution
- Characteristics of the disease in the peritoneum
How do low grade (type 1) carcinomas progress?
- Even after spread outside ovary, they progress slowly
- Patients survive for relatively long periods before dying of disease
What mutations are present in low grade tumors arising in serous borderline tumors?
- KRAS, BRAF, or ERBB2 oncogenes
- Usually have wild type TP53
How do high grade (type 2) carcinomas progress?
- Often widely metastatic throughout abdomen at the time of presentation
- Associated with rapid clinical deterioration
What mutations are present in high grade tumors?
- High frequency of TP53 mutations
- Lack of mutation in KRAS or BRAF
What are all ovarian carcinomas in women with BRCA1 or BRCA2 mutations?
- High grade serous carcinomas with TP53 mutations
How do mucinous tumors differ from serous tumors?
- Surface of the ovary is rarely involved
- Only 5% of primary mucinous cystadenomas and mucinous carcinomas are bilateral
What is a consistent genetic alteration in mucinous tumors of the ovary?
- Mutation of the KRAS proto-oncogene
What is seen with endometrioid carcinoma?
- In about 15%-20% of cases, there is endometriosis as well
- Peak incidence of tumors is a decade earlier than those without endometriosis
What other carcinoma is seen with endometrioid carcinoma?
- Carcinoma of the endometrium
- The relatively good prognosis in such cases suggests that the two arise independently
What is the presentation of most ovarian tumors?
- Weakness, weight loss –> cachexia
- Peritoneal disease –> ascites/omental cake
- With mets –> Liver, lungs, GI, opposite ovary
How is the diagnosis of an ovarian tumor made?
- Be clinically suspicious
- Imaging
- Tissue/cytology
- Staging by surgery or imaging
- Serum tumor markers +/-
What are the three categories of tertomas?
- Mature (benign)
- Immature (malignant)
- Monodermal or highly specialized
How are most benign teratomas?
- Cystic and referred to as dermoid cysts because they are almost always lined by skin-like structures
Who are cystic teratomas usually found?
- In young women during the active reproductive years
How are cystic teratomas usually found?
- Incidentally but are occasionally associated with clinically important paraneoplastic syndromes like inflammatory limbic encephalitis (may remit upon removal of tumor)
What are some specialized teratomas?
- Struma ovarii and carcinoid ovarian tumor
- Almost always unilateral
What is struma ovarii composed of?
- Mature thyroid tissue, which may be functional and cause hyperthyroidism
What do carcinoid tumors arise from?
- Intestinal tissue found in teratomas may also be functional
What can carcinoid tumors produce if large enough?
- 5HT to cause the carcinoid syndrome even in the absence of hepatic metastases because ovarian veins connect directly to the systemic circulation
How do immature malignant teratomas differ from benign teratomas?
- Components resemble embryonal and immature fetal tissue
Who is most likely to have an immature malignant teratoma?
- Prepubertal adolescents and young women (mean age is 18)
How is grading done for immature malignant teratomas?
- Based on the proportion of the tumor that is comprised of immature epithelium
What is a dysgerminoma?
- Ovarian counterpart of testicular seminoma
When does a dysgerminoma occur?
- May occur in childhood but 75% occur in the second and third decade
Who is most affected by dysgerminomas?
- Patients with gonadal dysgenesis like pseudohermaphroditism
What can dysgerminomas produce?
- Elevated levels of chorionic gonadotropin which correlates with the presence of syncytiotrophoblastic giant cells
What is a yolk sac tumor (endodermal sinus tumor)?
- Second most common malignant ovarian tumor of germ cell origin
- Though to be derived from malignant germ cells that are differentiating along the extraembryonic yolk sac lineage
What do the tumor cells in yolk sac tumors elaborate?
- a-fetoprotein
What do yolk sac tumors look like histologically?
- Glomerulus like structure composed of a central blood vessel enveloped by tumor cells within a space that is also lined by tumor cells (the Schiller-Duval body)
What are granulosa cell tumors comprised of?
- Cells that resemble granulosa cells of a developing ovarian follicle
- Broadly divided into adult and juvenile granulosa cell tumors based on age of patient
What age is most affected with granulosa cell tumors?
- May be discovered at any age, most occur in postmenopausal women
How would a adult granulosa cell tumor present?
- Dysfunctional Uterine Bleeding
- Endometrial hyperplasia
- Endometrial carcinoma
- Proliferative breast disease
How would a juvenile granulosa cell tumor present?
- Early breast development
- Early menarche
- Pubic or underarm hair
What do granulosa cell tumors look like?
- Usually unilateral and vary from microscopic foci to lare, solid, and cystic encapsulated masses
- Tumors that are hormonally active have a yellow coloration to their cut surfaces, due to intracellular lipids
What is histological diagnostic feature of granulosa cell tumors?
- Small, distinctive, glandlike structures filled with an acidophilic material that resemble immature follicles
- Called Call-Exnar bodies
What are fibromas?
- Unilateral tumors that are usually solid, spherical, or slightly lobulated, encapsulated, hard, gray-white masses covered by glistening, intact ovarian serosa
How do fibromas come to attention?
- As pelvic masses, sometimes associated by pain and two decidedly curious associations (ascites and basal cell nevus syndrome)
What is Meigs syndrome?
- Combination of ovarian tumor, hydrothorax, and ascites
What are sertoli-leydig cell tumors?
- Often functional
- Produce masculinization or defeminization but a few have estrogenic effects
- Recapitulate testicular sertoli or leydig cells at various stages of development
When is the peak incidence of sertoli-leydig cell tumors?
- Second and third decades
What do sertoli-leydig cell tumors cause?
- They block normal female sexual development in children
- May cause defeminization of women manifested by atrophy of breasts, amenorrhea, sterility, and loss of hair
- May progress to striking virilization associated with male hair distribution, hypertrophy of clitoris, and voice changes
What are hilus cell tumors?
- Rare, unilateral tumors comprised of large lipid-laden leydig cells with distinct borders and characteristic cytoplasmic structures called Reinke crystalloids
How do women with hilus cell tumors present?
- Evidence of masculinization (hirsutism, voice changes, and clitoral enlargement) but changes are milder than those seen in sertoli-leydig cell tumors
What is a gonadoblastoma?
- Uncommon tumor composed of germ cells and sex cord stromal derivatives resembling immature sertoli and granulosa cells
Who is affected by gonadoblastomas?
- Individuals with abnormal sexual development and in gonads of indeterminate nature (80% in phenotypic females and 20% in phenotypic males with undescended testes)
- Turner syndrome and Denys-Drash syndrome
What is the most common locations of tumors that metastasize to the ovaries?
- Lungs and GI
What is a tumor in the ovaries called that originated somewhere else?
- Krukenberg tumor
What is a histological appearance in some Krukenberg tumors?
- Signet ring appearance, most often from gastric mucosa
What is an ovarian torsion?
- Infrequent but significant cause of acute lower abdominal pain
- Peak median age of 28 and second peak of postmenopausal
- Fallopian tube is often involved
What can happen if ovarian torsion is not diagnosed and treated?
- Can lead to vascular compromise of adnexa and subsequent infarction
