Vaginal bleeding (Gianani)

Question 1

VAGINAL BLEEDING Background

Answer 1

Abnormal uterine bleeding describes a wide range of irregular bleeding patterns including acute or chronic heavy menstrual bleeding, abnormal duration of menstrual bleeding, as well as irregularities of menstrual cycle timing.

Causes include:
structural abnormalities, such as endometrial polyps, uterine fibroids, adenomyosis, or malignancy
coagulopathies or bleeding disorders
ovulatory dysfunction
iatrogenic sources, such as medications, smoking, or breakthrough bleeding with use of intrauterine device or noncompliance with hormonal contraceptives
chlamydia genital infection
physical or psychological stress, or eating disorder

Question 2

vaginal bleeding in pre-puberty

Answer 2

could be precocious puberty (hypothalamic, pituitary, or oarian origin)

Question 3

causes of vaginal bleeding in adolescence

Answer 3

anovulatory cycle, coagulation disorders

Question 4

causes of vaginal bleeding in reproductive age

Answer 4

complications of pregnancy(abortion, trophoblastic disease, ectopic pregnancy)
anatomic lesions (leiomyoma, adenomyosis, polyps, endometrial hyperplasa, carcinoma)
dysfunctional uterine bleeding- anovulatory cycle, ovulatory dysfunctional bleeding (e.g. inadequat luteal phase)

Question 5

causes of perimenopausal vaginal bleeding

Answer 5

dysfunctional uterine bleeding, anovulatory cycle, anatomic lesions (carcinoma, hyperplasia, polyps)

Question 6

postmenopausal

Answer 6

endometrial atrophy, anatomic lesions (carconoma, hyperplasia, polyps)

Question 7

rare cause of vaginal bleeding at any age

Answer 7

Anatomical lesions of vulva/vagina (Any age) (Not very common cause of vaginal bleeding)

Cervical cancer can result in vaginal bleeding or blood-stained vaginal discharge

Question 8

Amenorrhea

Answer 8

Primary amenorrhea - absence of menarche in females aged ≥ 15 years with normal secondary sexual development (or 5 years after initial breast development, which normally begins before 10 years of age)
- aged ≥ 13 years with no

secondary sexual characteristics
secondary amenorrhea - cessation of menstruation after menarche for 3 consecutive months in women with previously normal menstrual cycle (every 21-45 days)
– for 6 consecutive months in women with previously irregular menstrual cycle

Question 9

Primary ovarian insufficiency.

Answer 9

characterized by amenorrhea, delayed or absent menarche, or menopause before age 40 years.

results from depletion or dysfunction of ovarian follicles due to genetic, iatrogenic, autoimmune, or idiopathic causes.

also called premature ovarian dysfunction or failure, ovarian insufficiency, or premature menopause.

Untreated –> osteoporosis, hypercholesterolemia, cardiovascular disease, impaired sexual function, and impaired well-being.

Evaluation
Suspect this diagnosis characteristics who have not reached menarche by age 15 years, and women aged under 40 years with amenorrhea for ≥ 4 months or under 9 menses per year.
Exclude pregnancy as a cause of amenorrhea

Question 10

Hyperprolactinemia

Answer 10

Elevated serum prolactin level, a common condition which may be physiologic or pathologic
often due to pregnancy, medication, or prolactin-secreting pituitary tumor (prolactinoma)
can lead to hypogonadism, infertility, and galactorrhea

Definitions
pituitary tumors classified by size
- “micro” refers to tumor ≤ 10 mm in diameter (for example, microadenoma or microprolactinoma)
- “macro” refers to tumor > 10 mm in diameter
tumors in or near the pituitary that mimic prolactinomas may be referred to as “pseudoprolactinomas”

macroprolactin - a complex most often resulting from the binding of prolactin with immunoglobulin G (IgG) antibodies; the increased size of the polymer makes it unable to interact with prolactin receptor(macroprolactinemia - majority of circulating prolactin consists of macroprolactin; the polymeric form of prolactin produced by pituitary that has little to no biologic effect but tests positive on immunologic assays

Question 11

Polycistic Ovary Syndrome

Answer 11

Heterogeneous syndrome
may include some or all of
ovulatory dysfunction – anovulation, hyperandrogenism - acne, hirsutism
polycystic ovaries - on ultrasound
  obesity, hyperinsulinemia, infertility

Question 12

Endometrial Polyp

Answer 12

• exophytic masses of variable size that project into the endometrial cavity.
• single or multiple
• usually small and sessile, can be large and pedunculated.
• asymptomatic or may cause abnormal bleeding (intramenstrual, menometrorrhagia, or postmenopausal) if they ulcerate or undergo necrosis.

[Cytogenetic studies indicate that the stromal cells in endometrial polyps contain certain chromosomal rearrangements that are similar to those found in other benign mesenchymal tumors]

Question 13

Endometrial Carcinoma

Answer 13

most common invasive cancer of the female genital tract.

once endometrial carcinoma was far less common than cancer of the cervix, but earlier detection and eradi­cation of the precursor lesions of cervical carcinoma, coupled with an increase in endometrial carcinomas in younger women, have reversed this ratio.

There are Type I and Type II

Question 14

Malignant tumors of the endometrial epithelium

Answer 14

Endometrial Carcinoma.

Malignant Mixed Mullerian Tumor.

Question 15

Type I endometrial carcinoma - bullet points

Answer 15

age 55-65

unopposed estrogen, obesity, htn, diabetes

endometrioid morphology

hyperplasia precursor

genes: KRAS, PTEN

indolent, spreads via lymphatics

Question 16

Type II endometrial carcinoma - bullet points

Answer 16

age 65-75

atrophy, thin physique

serous, clear cell morphology; mixed muelleriean tumor

serous endometrial intraepithelial carcinoma precursor

genes: TP53
behavior: aggressive, intraperitoneal and lymphatic spread

Question 17

Non-atypical Hyperplasia.

Answer 17

Hyperplasia without atypia

• increased glandular crowding with areas of back-to-back glands and cytologic features similar to proliferative endometrium.
• wide-range of appearances,
• cardinal feature: an increase in the gland-to-stroma ratio. The glands show variation in size and shape and may be dilated
• reflect an endometrial response to persistent estrogen stimulation and rarely progress to adenocarcinoma.
• Non-atypical hyperplasia may evolve into cystic atrophy when estrogen is withdrawn.

Question 18

Atypical hyperplasia

Answer 18

• Atypical hyperplasia with further increase in glandular crowding and abnormal cytologic features.
• rounded, vesicular nuclei with prominent nucleoli
• complex patterns of proliferating glands displaying nuclear atypia. The glands are commonly back-to-back and often have complex outlines due to branching structures.
• Individual cells are rounded and lose the normal perpendicular orientation to the basement membrane.
• nuclei have open (vesicular) chromatin and conspicuous nucleoli.
• The features have considerable overlap with those of well-differentiated endometrioid adenocarcinoma, and accurate distinction from cancer may not be possible without hysterectomy.
• 23% to 48% of women with a dx of atypical hyperplasia are found to have carcinoma when a hysterectomy is performed.

Question 19

Type I Endometrial carcinoma.

Answer 19

• most common type,
• Most are well differentiated and mimic proliferative endometrial glands; = endometrioid carcinoma.
• typically arise in the setting of endometrial hyperplasia and associated with
  (1) obesity,
  (2) diabetes
  (3) hypertension,
  (4) infertility,
  (5) unopposed estrogen stimulation.
• involves the stepwise acquisition of several genetic alterations in tumor suppressor genes and oncogenes.

atypical hyperplasia+ PTEN mutations–> carcinoma

Question 20

frequent growth pattern of serous carcinoma

Answer 20

papillary

Question 21

endometrial adenocarinoma grades

Answer 21

well differentiated (grade 1), 
- composed almost entirely of well-formed glands; 

moderately differentiated (grade 2), showing well-formed glands mixed with areas composed of solid sheets of cells, which by definition make up 50% or less of the tumor; and

poorly differentiated (grade 3), characterized by greater than 50% solid growth pattern.

• Well differentiated tumors may be distinguished from hyperplasias by lack of intervening stroma.

Question 22

Pathologic staging of both type I and II endometrial adenocarcinoma and malignant mixed müllerian tumors (described later) is as follows:

Answer 22

Stage I—Carcinoma is confined to the corpus uteri itself.
Stage II—Carcinoma involves the corpus and the cervix.
Stage III—Carcinoma extends outside the uterus but not outside the true pelvis.
Stage IV—Carcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum.

Question 23

Tumors of the endometrial stroma

Answer 23

Adenosarcoma

Stromal tumor

Question 24

Adenosarcomas

(not important)

Answer 24

present commonly as large broad-based endometrial polypoid growths that may prolapse throught eh cervical os. dx based on presence of malignan-appearing stroma, which coexists with benign but abnormally shaped endometrial glands. These tumors predominate in women betw the 4th and 5th decades and are generally considered to be a low-grade malignancy; recurrences develop in one fourth of cases and are nearly always confined to the pelvis
principal dx dilemma is distinguishing these tumors from large benign polyps. The distinction is important, because adenosarcoma is estogen-sensitive and responds to oophorectomy.

Question 25

Stromal sarcomas

Answer 25

the endometrium occasionally gives rise to neoplasms that resemble normal stromal cells. Endometrial stromal neoplasms are divided into two categories:

1. benign stroma nodules and
2. endometrial stromal sarcomas.

the stromal sarcomas may be further divided into low-grade and high-grade types depending on their differentiation.

Question 26

Tumors of the Myometrium

Answer 26

Begnin tumor of the myometrium.

Malignant tumor of the myometrium

Question 27

Leyomyosarcoma

Answer 27

Malignant tumor of the myometrium

necrosis
cytological atypia
mitological activity