Pbl Exam 10 Case 5

Front 1

1.What are the two major phases of female reproductive functions?

Back 1

1. Preparation of the female body for conception and pregnancy

2. The period of pregnancy itself

Front 2

2. What are the steps of the female reproductive system?

Back 2

1. Reproduction begins with the development of ova in the ovaries
2. In the middle of each monthly sexual cycle, a single ovum is expelled from an ovarian follicle into the abdominal cavity near the open fimbriated ends of the two fallopian tubes.
3. This ovum then passes through one of the fallopian tubes into the uterus
4. If the ovum has been fertilized by a sperm, it implants in the uterus, where it develops into a fetus, a placenta, and fetal membranes, and eventually into a baby.

Front 3

3. How does the ovum become an oocyte?

Back 3

1. During fetal life, the outer surface of the ovary is covered by a germinal epithelium, which embryologically is derived from the epithelium of the germinal ridges.
2. As the fetus develops, primordial ova differentiate from this germinal epithelium and migrate into the substance of the ovarian cortex.
3. Each ovum then collects around it a layer of spindle cells from the ovarian stroma, and causes them to take on epitheliod characteristics; they are then called granulosa cells.
4. The ovum surrounded by a single layer of granulosa cells is called a primordial follicle.
5. The ovum at this stage is still immature, requiring two more cell divisions before it can be fertilized by a sperm. At this time, ovum is called a primary oocyte.

Front 4

4. What are the 3 hierarchies of hormones in the female?

Back 4

1. A hypothalamic releasing hormone, gonadotropin-releasing hormone (GnRH)
2. The anterior pituitary sex hormones, follicle stimulating hormone (FSH), and luteinizing hormone (LH), both of which are secreted in response to the release of GnRH
3. The ovarian hormones, estrogen and progesterone, which are secreted by the ovaries in response to the two female sex hormones from the anterior pituitary gland.

Front 5

5. What is the female monthly sexual cycle?

What are the two significant results of the cycle?

Back 5

The rhythmical pattern of female hormone secretion is called the female monthly sexual cycle, AKA menstrual cycle.

The duration of the cycle averages 28 days; it may be as short as 20 or a long as 45.

The two significant results are:
1. Only a single ovum is normally released from the ovaries each month, so that normally only a single fetus will begin to grow at a time.
2. The uterine endometrium is prepared in advance for implantation of the fertilized ovum at the required time of the month.

Front 6

6. What are the effects of the gonadotropic hormones on the ovaries?

Back 6

The ovarian chances that occur during the menstrual cycle depend completely on FSH and LH.

At age 9-12, the pituitary begins to secrete progressively more FSH and LH, which leads to onset of normal monthly sexual cycles beginning between the ages of 11 and 15 years.

During each month of the cycle, there is a cyclical increase and decrease of both FSH and LH.

Front 7

7. How do FSH and LH stimulate their ovarian target cells?

Back 7

They combine with highly specific FSH and LH receptors int he ovarian target cell membranes.

In turn, the activated receptors increase the cells' rates of secretion and usually the growth and proliferation of the cells as well.

Almost all thees stimulatory effects result form activation of cAMP in the cell cytoplasm, which causes the formation of protein kinase and multiple phosphorylations of key enzymes that stimulate sex hormone synthesis.

Front 8

8. What is the primordial follicle?

Back 8

When a female child is born, each ovum is surrounded by a single layer of granulosa cells; the ovum, with this granulosa cell sheath, is called a primordial follicle.

Front 9

9. What is the purpose of the oocyte maturation inhibiting factor?

From where is this inhibiting factor secreted?

Back 9

The granulosa cells are believed to provide nourishment for the ovum and to secrete an oocyte maturation inhibiting factor that keeps the ovum suspended in its primordial state in the prophase stage of meiotic division.

Front 10

10. What is a primary follicle?

Back 10

After puberty, when FSH and LH from the anterior pituitary gland begin to be secreted, the ovaries within then begin to grow.

The first stage of follicular growth is moderate enlargement of the ovum itself, which increases in diameter 2-3xx.

Then follows growth of additional layers of granulosa cells in some of the follicles; these follicles are known as primary follicles.

Front 11

11. What is the theca?

Back 11

In response to LH and FSH, 6-12 primary follicles grow rapidly each month. The initial effect is rapid proliferation of the granulosa cells, giving rise to many more layers of these cells.

In addition, spindle cells derived from the ovary interstitium collect in several layers outside the granulosa cells, giving rise to a second mass of cells called the theca.

This is divided into two layers, the theca interna, and the theca externa.

Front 12

12. What are the characteristics of the theca interna/externa?

Back 12

The theca interna takes on epithelioid characteristics similar to those of the granulosa cells and develop the ability to secrete additional steroid sex hormones (estrogen and progesterone).

The outer layer, the theca externa, develops into a highly vascular connective tissue capsule that becomes the capsule of the developing follicle.

Front 13

13. What is the antrum?

The early growth of the primary follicle up to the antral stage is stimulated by...?

Back 13

After the early proliferative phase of growth, the mass of granulosa cells secretes a follicular fluid that contains a high concentration of estrogen.

Accumulation of this fluid causes an antrum to appear within the mass of granulosa cells.

*The early growth of the primary follicle up to the antral stage is stimulated mainly by FSH alone. This leads to larger follicles called vesicular follicles.

Front 14

14. The accelerated growth of the vesicular follicles is caused by what three things...?

Back 14

1. Estrogen is secreted into the follicle and causes the granulosa cells to form increasing numbers of FSH receptors.
2. The pituitary FSH and the estrogens combine to promote LH receptors on the original granulosa cells, thus allowing LH stimulation to occur in addition to FSH stimulation and creating an even more rapid increase in follicular secretion.
3. The increasing estrogens from the follicle plus the increasing LH from the anterior pituitary gland act together to cause proliferation of the follicular thecal cells and increase their secretion as well.

Front 15

15. How many follicles fully mature each month?

What causes atresia?

Back 15

Only one; the remaining 5-11 developing follicles involute and they are said to become atretic.

The large amts of estrogen from the most rapidly growing follicle act on the hypothalamus to depress further enhancement of FSH secretion by the anterior pituitary gland, in this way blocking further growth of the less well developed follicles.

Therefore, the largest follicle continues to grow b/c of its intrinsic positive feedback effects, while all the other follicles stop growing and actually involute.

Front 16

16. Why is atresia important?

Back 16

It normally allows only one of the follicles to grow large enough each month to ovulate; this usually prevents more than one child from developing with each pregnancy.

Front 17

17. What is the stigma?

What is the corona radiata?

Back 17

Shortly before ovulation, the protruding outer wall of the follicles swells rapidly, and a small area in the center of the follicular capsule, called the stigma, protrudes like a nipple.

In another 30 min or so, fluid begins to ooze from the follicle through the stigma, and about 2 min later, the stigma ruptures widely, allowing a more viscous fluid, which as occupied the central portion of the follicle, to evaginate outward.

This viscous fluid carries with it the ovum surrounded by a mass of several thousand small granulosa cells, called the corona radiata.

Front 18

18. A surge in what hormone is necessary for ovulation?

What three factors contribute to the initiation of ovulation?

Back 18

Surge of LH is necessary for final follicular growth and ovulation.

1. Rapid growth of the follicle
2. Diminishing estrogen secretion after a prolonged phase of excessive estrogen secretion
3. Initiation of secretion of progesterone that causes ovulation to occur.

W/o the initial pre-ovulatory surge of LH, ovulation will not take place.

Front 19

19. The initiation of ovulation caused by LH leads to...?

What two events are necessary for ovulation to occur? Why?

Back 19

Causes rapid secretion of the follicular steroid hormones that contain progesterone. Within a few hours; two events occur, both of which are necessary for ovulation:

1. The theca externa (capsule of the follicle) begins to release proteolytic enzymes from lysosomes, and these cause dissolution of the follicular capsular wall and consequent weakening of the wall, resulting in further swelling of the entire follicle and degeneration of the stigma.
2. Simultaneously, there is rapid growth of new blood vessels into the follicle wall, and at the same time, prostaglandins are secreted into the follicular tissues.

These two effects cause plasma transudation into the follicle, which contributes to follicle swelling. Finally, the combo of follicle swelling and simultaneous degeneration of the stigma causes follicle rupture, with discharge of the ovum.

Front 20

20. What are lutein cells? What is luteinization?

Back 20

During the first few hours after expulsion of the ovum from the follicle, the remaining granulosa and theca interna cells change rapidly into lutein cells.

They enlarge in diameter two or more times and become filled with lipid inclusions that give them a yellowish appearance. This process is called luteinization, and the total mass of cells together is called the corpus luteum, which has a well developed vascular supply.

Front 21

21. The granulosa cells in the corpus luteum develop...?

Back 21

They develop extensive intracellular smooth ER that form large amts of progesterone and estrogen.

The theca cells form mainly the androgens androstenedione and testosterone. However, most of these hormones are also converted by the granulosa cells into the female hormones.

Front 22

22. What is the corpus albicans?

Back 22

The corpus luteum grows to 1.5 cm about 7-8 days after ovulation.

Then it begins to involute and eventually loses its secretory function as well as its yellowish, lipid characteristic about 12 days after ovulation, becoming the corpus albicans.

During the next few weeks, this is replaced by connective tissue and then is absorbed.

Front 23

23. What is the function of LH?

Back 23

It "leuteinizes".

The change of granulosa and theca interna cells into lutein cells is dependent mainly on LH secreted by the anterior pituitary gland.

Luteinization also depends on extrusion of the ovum from the follicle. A local hormone in the follicular fluid, called luteinization-inhibiting factor, seems to hold the luteinization process in check until after ovulation.

Front 24

24. What effect does LH have on the corpus luteum?

What are the four stages of luteinization?

Back 24

The corpus luteum is highly secretory, secreting large amts of both progesterone and estrogen.

Once LH has acted on the granulasa and theca cells to cause luteinization, the newly formed lutein cells seemed to be programmed to go through a preordained sequence that occurs in 12 days:

1. Proliferation
2. Enlargement
3. Secretion
4. Degeneration

Front 25

25. Estrogen and progesterone secreted by the corpus luteum have what effects on the ovarian cycle?

Back 25

They have strong feedback effects on the anterior pituitary gland to maintain low secretory rates of both FSH and LH.

Front 26

26. What is inhibin? What does its secretion result in?

Back 26

The lutein cells secrete small amts of the hormone inhibin, the same as the inhibin secreted by the Sertoli cells of the male testes.

This hormone inhibits secretion by the anterior pituitary gland, especially FSH secretion.

Low blood concentrations of both FSH and LH result, and loss of these hormones finally causes the corpus luteum to degenerate completely via involution.

Front 27

27. The involution process involves what?

Back 27

At this time, the sudden cessation of secretion of estrogen, progesterone, and inhibin by the corpus luteum removes the feedback inhibition of the anterior pituitary gland, allowing it to begin secreting increasing amts of FSH and LH again.

FSH and LH initiate the growth of new follicles, beginning a new ovarian cycle.

Front 28

28. What are the estrogens/progestins, which are most important, and what do they do?

Back 28

Two two types of ovarian hormones are the estrogens and the progestins. By far the most important estrogen is the hormone estradiol, and the most important progestin is progesterone.

The estrogens mainly promote proliferation and growth of specific cells in the body that are responsible for the development of most secondary sexual characteristics of the female.

The progestins function mainly to prepare the uterus for pregnancy and the breasts for lactation.

Front 29

29. What three estrogens are present in significant quantities in the plasma of the human female?

Which is more potent?

Back 29

β-estrodiol, estrone, and estriol.

The principal estrogen secreted by the ovaries is β-estrodiol. Small amts of estrone are also secreted but most of this is formed in peripheral tissues from androgens secreted by the adrenal cortices and by ovarian thecal cells. Estriol is a weak estrogen, ti is an oxidative product derived from both estradiol and estrone.

β-estradiol is 12x more potent than estrone and 80x more than estriol.

Front 30

30. What are the progestins present in the human female?

Back 30

By far the most important is progesterone. However, small amts of 17-α-hydroxyprogesterone are secreted with progesterone and have essentially the same effects.

In the normal nonpregnant female, progesterone is secreted in significant amts only during the latter half of each ovarian cycle, when it is secreted by the corpus luteum.

During pregnancy, large amts of progesterone are also secreted by the placenta especially after the fourth month of gestation.

Front 31

31. How are the progestins and estrogens synthesized?

Back 31

They are all steroids, maining they are formed from cholesterol in the blood but also to a slight extent from acetyl coenzyme A.

During synthesis, mainly progesterone and the male sex hormones are synthesized first; then, during the follicular phase of the ovarian cycle, almost all the testosterone and much of the progesterone are converted into estrogens by the granulosa cells.

During the luteal phase of the cycle, far too much progesterone is formed for all of it to be converted, which accounts for the large secretion of progesterone into the circulating blood at this time.

Front 32

32. How are the progestins and estrogens transported in the blood?

Back 32

They are bound mainly w/plasma albumin and w/specific estrogen and progesterone binding globulins.

The binding is loose enough that they are rapidly released to the tissues over a period of 30 min or so.

Front 33

33. What is the function of the liver in estrogen metabolism?

Back 33

The liver conjugates the estrogens to form glucuronides and sulfates, and about 15 of these conjugated products is excreted in the bile; most of the remainder is excreted in the urine.

Also, the liver converts the potent estrogens estradiol and estrone into the almost totally impotent estrogen estriol.

Therefore, diminished liver function actually increases the activity of estrogens in the body, sometimes causing hyperestrinism.

Front 34

34. What is the fate of progesterone?

Back 34

Within a few min after secretion, almost all the progesterone is degraded to other steroids that have no progestational effect.

The major end product of progesterone degradation is pregnanediol. About 10% of the original progesterone is excreted in the urine in this form.

Front 35

35. What are the effects of estrogens on the uterus and female sex organs?

Back 35

During puberty, the ovaries, fallopian tubes, uterus, and vagina all increase several times in size.

Also, the external genitalia enlarge with deposition of fat in the mons pubis and labia majora and enlargement of the labia minora.

During the first few years after puberty, the size of the uterus increases 2-3x but more important that the increase in uterus size are the changes that take place in the uterine endometrium under the influence of estrogens. As such, there is marked proliferation of the endometrial stroma and greatly increased development of the endometrial glands.

Front 36

36. What transformation occurs in the vaginal epithelium during puberty as a result of estrogens?

Back 36

Estrogens change the vaginal epithelium from a cuboidal into a stratified type, which is considerably more resistant to trauma and infection than is the prepubertal cuboidal cell epithelium.

Vaginal infections in children can often be cured by the administration of estrogens.

Front 37

37. Effects of estrogens on the fallopian tubes?

Back 37

They cause the glandular tissues of this lining to proliferate; especially important, they cause the number of ciliated epithelial cells that line the fallopian tubes to increase.

Also, activity of the cilia is considerably enhanced. These cilia always beat toward the uterus, which helps propel the fertilized ovum in that direction.

Front 38

38. Effects of estrogens on the breasts?

Back 38

Estrogens cause (1) development of the stromal tissues of the breasts, (2) growth of an extensive ductile system, and (3) deposition of fat in the breasts.

The lobules and alveoli of the breast develop to a slight extent under the influence of estrogens alone, but it is progesterone and prolactin that cause the ultimate determinative growth and function of these structures.

Front 39

39. Effects of estrogens on the skeleton?

Back 39

Estrogens inhibit osteoclastic activity in the bones and therefore stimulate bone growth.

They also cause uniting of the epiphyses w/the shafts of the long bones, and as a result, growth of the female usually ceases several years earlier than growth of the male.

Front 40

40. After menopause, a deficiency in estrogen leads to...?

Back 40

1. Increased osteoclastic activity in the bones
2. Decreased bone matrix
3. Increased deposition of bone calcium and phosphate

Leads to osteoporosis.

Front 41

41. Effect of estrogens on protein deposition?

Back 41

Estrogens cause a slight increase in total body protein, which causes a slight positive nitrogen balance when estrogens are administered.

Front 42

42. Effect of estrogens on body metabolism and fat deposition?

Back 42

Estrogens increase the whole-body metabolic rate slightly but only about 1/3 that of the increase caused by testosterone.

They also cause deposition of increased quantities of fat in the subcutaneous tissues, especially in the buttocks and thighs.

Front 43

43. Effect of estrogens on hair distribution?

Back 43

They do not greatly affect hair distribution.

However, hair does develop in the pubic region and in the armpits after puberty. Androgens formed in increased quantities by the female adrenals causes this.

Front 44

44. Effect of estrogens on the skin?

Back 44

They cause the skin to develop a texture that is soft and usually smooth, but it is thicker than that of a child or a castrated female.

Also, they cause the skin to become more vascular; this is assoc with increased warmth of the skin and also promotes greater bleeding of cut surfaces than is observed in men.

Front 45

45. Effect of estrogens on electrolyte balance?

Back 45

Estrogenic hormone are similar to adrenocortical hormones. As such they also cause sodium and water retention by the kidney tubules.

Front 46

46. Effect of progesterone on the uterus?

Back 46

The most important function is to promote secretory changes in the uterine endometrium during the latter half of the monthly female sexual cycle, thus preparing the uterus for implantation of the fertilized ovum.

It also decreases the freq and intensity of uterine contraction, thereby helping to prevent expulsion of the implanted ovum.

Front 47

47. Effect of progesterone on the fallopian tubes?

Back 47

Progesterone also increases secretion by the mucosal lining of the fallopian tubes.

These secretions are necessary for nutrition of the fertilized, dividing ovum as it traverses the fallopian tube before implantation.

Front 48

48. Effect of progesterone on the breasts?

Back 48

They promote development of the lobules and alveoli of the breasts, causing the alveolar cells to proliferate, enlarge, and become secretory in nature.

However, they do not cause milk secretion, this is prolactins job.

Progesterone also causes the breast to swell in part due to increased fluid in the tissue.

Front 49

49. What are the three stages of the endometrial cycle?

Back 49

1. Proliferation of the uterine endometrium
2. Development of secretory changes in the endometrium
3. Desquamation of the endometrium, AKA menstruation

Front 50

50. What is the purpose of all these endometrial changes?

Back 50

To produce a highly secretory endometrium that contains large amts of stored nutrients to proved appropriate conditions for implantation of a fertilized ovum during the latter half of the monthly cycle.

Front 51

51. What is menstruation?

What causes menstruation?

Back 51

If the ovum is not fertilized, about 2 days before the end of the monthly cycle, the corpus luteum in the ovary suddenly involutes, and the ovarian hormones decreased to low levels and menstruation follows.

Menstruation is caused by the reduction of estrogens and progesterone, especially progesterone at the end of the monthly cycle. As a result, there is rapid involution and vasospasm of the blood vessels. The vasospasm, decrease in nutrients, and loss of hormonal stimulation initiates necrosis in the endometrium.

Front 52

52. What occurs during menstruation?

Back 52

Blood at first seeps into the vascular layers of the endometrium, and the hemorrhagic areas grow rapidly. Gradually, the necrotic outer layers separate from the uterus until all the superficial layers of the endometrium have been desquamated.

The mass of desquamated tissue and blood in the uterine cavity, plus contactile effects of prostaglandins or other substances act together to initiate uterine contractions that expel the uterine contents.

Front 53

53. Why does menstrual fluid not clot?

Back 53

The menstrual fluid is normally nonclotting b/c a fibrinolysin is released along with the necrotic endometrial material.

Front 54

54. Why does leukorrhea occur during menstruation?

Back 54

During menstruation, tremendous amts of leukocytes are released along w/the necrotic material and blood.

It is probably that some substances liberated by the endometrial necrosis causes this outflow of leukocytes. As a result of these leukocytes, the uterus is highly resistant to infection during menstruation; this is of extreme protective value.

Front 55

55. What stimulates pulsatile release of LH from the anterior pituitary?

Back 55

Intermittent, pulsatile secretion of GnRH by the hypothalamus stimulates pulsatile release of LH from the anterior pituitary.

*Continuous administration of GnRH does not cause the release of LH and FSH; only intermittent release.

Front 56

56. Where does the neuronal activity that causes pulsatile release of GnRH occur?

Back 56

Primarily in the mediobasal hypothalamus, especially in the arcuate nuclei of this area. Therefore, it is believed that these arcuate nuclei control most female sexual activity.

Since multiple neuronal centers in the limbic system transmit signals into the arcuate nuclei, this partially explains why psychic factors often modify female sexual function.

Front 57

57. Estrogens in large amounts does what...

Back 57

They have a strong effect to inhibit the production of both LH and FSH.

Also, when progesterone is available, the inhibitory effect of estrogen is multiplied.

These feedback effects seem to operate mainly on the anterior pituitary gland directly, but they also operate to a lesser extent on the hypothalamus to decrease secretion of GnRH, especially by altering the freq of the GnRH pulses.

Front 58

58. What are the 2 suggested causes of the preovulatory surge in LH?

Back 58

1. Estrogen at this point in the cycle has a peculiar positive feedback effect of stimulating pituitary secretion of LH, and to a lesser extent, FSH; this is in sharp contrast to its normal negative feedback effect that occurs during the remainder of the monthly cycle.
2. The granulosa cells of the follicles begin to secrete small but increasing quantities of progesterone a day or so before the preovulatory LH surge.

Front 59

59. Postovulatory secretion of the ovarian hormones cause...?

Back 59

All these hormones together have a combined negative feedback effect on the anterior pituitary and hypothalamus, causing the suppression of both FSH and LH secretion, and decreasing them to their lowest levels about 3-4 days before the onset of menstruation.

Front 60

60. What hormone levels are increased/decreased during the follicular growth phase?

Back 60

The hypothalamus and anterior pituitary are released from negative feedback and therefore, pituitary secretion of FSH begins to increase again, as much as 2x, and then several days after menstruation begins, LH secretion increases slightly as well.

These hormones initiate new ovarian follicle growth and a progressive increase in the secretion of estrogen, reaching a peak estrogen secretion at about 12.5-13 days after the onset of the new menstrual cycle.

During the first 11-12 days of this follicle growth, the rates of pituitary secretion of FSH and LH decrease slightly b/c of the negative feedback effect of estrogen. Then, there is a sudden, marked increase in the secretion of LH and FSH.

Front 61

61. Specifically, what hormone surge(s) causes ovulation?

Back 61

Preovulatory surge of LH and FSH causes ovulation. At about 11.5 to 12 days after the onset of the cycle, the decline in secretion of FSH and LH comes to an abrupt halt.

It is believed that the high level of estrogens at this time causes a positive feedback stimulatory effect on the anterior pituitary, which leads to a surge in the secretion of LH and, to a lesser extent, FSH.

Front 62

62. What does anovulatory mean?

Back 62

If the preovulatory surge of LH is not of sufficient magnitude, ovulation will not occur, and the cycle is said to be "anovulatory".

The phases of the sexual cycle continue, but they are altered in the following ways:
1. The corpus luteum does not form due to no ovulation, and thus there is no secretion of progesterone.
2. The cycle is shortened by several days, bu the rhythm continues.

The first few cycles after the onset of puberty are usually anovulatory, as are the cycles occurring several months to years before menopause.

Front 63

63. Puberty and menarche

Why does hypothalamus's not secrete GnRH in childhood?

Back 63

Puberty means the onset of adult sexual life, and menarche means the beginning of the cycle of menstruation.

The period of puberty is caused by a gradual increase in gonadotropic hormone secretion by the pituitary.

It is believed that the hypothalamus is capable of secreting GnRH during childhood, however, it does not. Supposedly, the onset of puberty is initiated by some maturation process that occurs elsewhere in the brain, perhaps in the limbic system.

Front 64

64. What are the five characteristics of estrogen secretion throughout the sexual life of the female human?

Back 64

1. Increasing levels of estrogen secretion at puberty
2. The cyclical variation during the monthly sexual cycle
3. The further increase in estrogen secretion during the first few years of reproductive life
4. The progressive decrease in estrogen secretion toward the end of reproductive life
5. Almost no estrogen or progesterone secretion beyond menopause

Front 65

65. What is menopause?

What causes it?

Back 65

At about 40-50 years, the sexual cycle becomes irregular, and ovulation often fails to occur. After a few month or years, the cycle ceases altogether.

The cause is "burning out" of the ovaries. At about age 45, only a few primordial follicles remain to be stimulated by FSH and LH, and the production of estrogens by the ovaries decreases as the number of primordial follicles approaches zero.

Front 66

66. What are the physiologic changes that occur during menopause?

Back 66

1. Hot flushes
2. Psychic sensations
3. Irritability
4. Fatigue
5. Anxiety
6. Occasionally various psychotic states
7. Decreased bone strength and calcification of bones throughout the body

*Administration of exogenous estrogen in small quantities daily usually reverses the symptoms.

Front 67

67. What is hypogonadism?

What is female eunuchism?

Back 67

Less than normal secretion by the ovaries can result from poorly formed ovaries, lack of ovaries, or genetically abnormal ovaries that secrete the wrong hormones b/c of missing enzymes in the secretory cells.

When ovaries are absent from birth or when they become nonfunctional before puberty, female eunuchism occurs.

Front 68

68. What do eunuch females look like?

Back 68

In this condition, the usual secondary sexual characteristics do not appear, and the sexual organs remain infantile.

Especially characteristic is the prolonged growth of the long bones b/c the epiphyses do not unite w/the shafts as early as they do in a normal women. Thus, the female eunuch is taller.

Front 69

69. How does hypogonadism effect the menses?

Back 69

In hypogonadism or when the gonads are secreting small quantities of estrogens as a result of other factors, such as hypothyroidism, the ovarian cycle often does not occur normally.

Instead, several months may elapse between menstrual periods, or menstruation may cease altogether.

Prolonged ovarian cycles are freq associated w/failure of ovulation, presumably b/c of insufficient secretion of LH at the time of the preovulatory surge of LH.

Front 70

70. When does hypersecretion by the ovaries occur?

Back 70

Extreme hypersecretion of ovarian hormones by the ovaries is rare, b/c excessive secretion of estrogens automatically decreases the production of gonadotropins by the pituitary, and this limits the production of ovarian hormones.

Consequently, hypersecretion of feminizing hormones is usually recognized clinically only when a feminizing tumor develops.

Front 71

71. What is a granulosa cell tumor?

Back 71

A rare granulosa cell tumor can develop in an ovary, occurring more often after menopause then before.

These tumors secrete large quantities of estrogens, which exert the usual estrogenic effects, including hypertrophy of the uterine endometrium and irregular bleeding from the endometrium. In fact, bleeding is often the first and only indication that such a tumor exists.

Front 72

72. Where do the nerves synapse that innervate the female erectile tissue?

Release of what factors causes erection?

Back 72

The erectile tissue is controlled by the parasympathetic nerves that pass thru the nervi erigentes from the sacral plexus to the external genitalia.

In the early phases of sexual stimulation, parasympathetic signals dilate the arteries of the erectile tissue, probably resulting from the release of ACh, NO, and vasoactive intestinal polypeptide at the nerve endings.

Front 73

73. Why is the female orgasm important for fertilization?

Back 73

During the orgasm, the perineal muscles of the female contract rhythmically; it is possible that these reflexes increase uterine and fallopian tube motility during the orgasm, thus helping transport the sperm upward thru the uterus toward the ovum. Also, the orgasm seems to cause dilation of the cervical canal for up to 30 min, thus allowing easy transport of the sperm.

In addition, copulation causes the posterior pituitary gland to secrete oxytocin; this causes increased rhythmical contractions of the uterus, which is thought to cause increased transport of the sperm.

Front 74

74. What is the fertile period of each female sexual cycle?

Back 74

The ovum remains viable and capable of being fertilized after it is expelled form the ovary probably no longer than 24 hours.

Therefore, sperm must be available soon after ovulation if fertilization is to take place. In other words, intercourse must occur sometime between 4 and 5 days before ovulation up to a few hours after ovulation.

Front 75

75. What is the rhythm method of contraception?

Back 75

It is usually stated that avoidance of intercourse for 4 days before the calculated day of ovulation and 3 days afterward prevents conception.

But such a method of contraception can be used only when the periodicity of the menstrual cycle is regular.

Front 76

76. Why does the pill work?

Back 76

The reason for this is that appropriate administration of either of these hormones (estrogen or progesterone) can prevent the preovulatory surge of LH secretion by the pituitary gland, which is essential in causing ovulation.

Immediately before the LH surge occurs, there is probably a sudden depression of estrogen secretion by the ovarian follicles, and this might be the necessary signal that causes the subsequent feedback effect on the anterior pituitary that leads to the LH surge. The administration of sex hormones (estrogens or progesterone) could prevent the initial ovarian hormonal depression that might be the initiating signal for ovulation.

Front 77

77. Why are natural hormones not used in the pill?

Back 77

The natural hormones are almost entirely destroyed by the liver within a short time after they are absorbed from the GI tract into the portal circulation.

However, many of the synthetic hormones can resist this destructive propensity of the liver, thus allowing oral administration.

Front 78

78. What abnormal conditions cause female sterility?

Back 78

The most common cause is failure to ovulate; this can result from hyposecretion fo gonadotropic hormones, in which case the intensity of the hormonal stimuli is simply insufficient to cause ovulation, or it can result from abnormal ovaries that do not allow ovulation.

Front 79

79. What are some ways to test for female sterility?

Back 79

One way to is analyze the urine for a surge in pregnanediol, the end product of progesterone metabolism, during the latter half of the sexual cycle; the lack of this substance indicated failure of ovulation.

Another common test is for the woman to chart her body temp throughout the cycle. Secretion of progesterone during the latter half of the cycle raises the body temp about half a degree, with the temp rise combing abruptly at the time of ovulation.

Front 80

80. What is one way to treat lack of ovulation caused by hyposecretion of the pituitary gonadotropic hormones?

Back 80

Can sometimes be treated w/ appropriately timed administration of human chorionic gonadotropin. This hormone, although secreted by the placenta, has almost the same effects as LH and is therefore a powerful stimulator of ovulation.

However, excess use of this hormone can cause ovulation from many follicles simultaneously.

Front 81

81. What is endometriosis?

Back 81

A common cause of female sterility, in which the endometrial tissue almost identical to that of the normal uterine endometrium grows and even menstruates in the pelvic cavity surrounding the uterus, fallopian tubes, and ovaries.

It causes fibrosis throughout the pelvis, and this fibrosis sometimes so covers the ovaries that an ovum cannot be released into the abdominal cavity.

Front 82

82. What is salpingitis?

Back 82

Inflammation of the fallopian tubes; this causes fibrosis in the tubes, thereby occluding them.

In the past this was from gonococcal infection.

Front 83

83. Abnormal mucus secretion by the uterine cervix can cause…?

Back 83

Infertility. Ordinarily, at the time of ovulation, the hormonal environment of estrogen causes the secretion of mucus w/special characteristics that allow rapid motility of sperm into the uterus and actually guide the sperm up along mucous threads.

Abnormalities of the cervix itself, such as low grade infection or inflammation, or abnormal hormonal stimulation of the cervix can lead to a viscous mucous plug that prevents fertilization.

Front 84

84. What is trichomonas vaginalis?

Back 84

Trichomonas vaginalis is a large, flagellated ovoid protozoan that can be readily identified in wet mounts of vaginal discharge in infected pts. Infections may occur at any age and are seen in about 15% of women in sexually transmitted disease clinics.

It is associated with a purulent vaginal discharge and discomfort the underlying vaginal and cervical mucosa typically has a characteristic fiery red appearance, called strawberry cervix.

Front 85

85. What is pelvic inflammatory disease (PID)?

Back 85

PID is a common disorder characterized by pelvic pain, adnexal tenderness, fever, and vaginal discharge; it results from infection by one or more of the following groups of organisms: gonococci, chlamydiae, and enteric bacteria.

Besides these, infections after spontaneous or induced abortions and normal or abnormal deliveries (called puerperal infections) are improtant in the production of PID. Such PID is polymicrobial and is caused by staphylococci, streptococci, coliform bacteria, and C. perfringens.

Front 86

86. What are the symptoms of PID caused by gonococci?

Back 86

Gonococcal inflammation usually begins in the Bartholin gland and other vestibular glands or periurethral glands; cervix involvement is common and freq asymptomatic.

From any of these sites, the organissm may spread upward to invovle the tubes and tubo-ovarian region.

The adult is more resistant to the gonococcus but the child may develop vulvo-vaginitis.

Front 87

87. What are the symptoms of PID caused by puerperal infections?

Back 87

The nongonococcal bacterial infections that follow induced abortion, dilation, and curettage of the uterus, and other surgical procedures on the female genital tract are thought to spread from the uterus upward thru the lymphatics or venous channels rather than on the mucosal surfaces.

These infections therefore tend to produce less mucosal involvement but more reaction w/in the deeper layers.

Front 88

88. What is the morphology of gonococcal PID?

Back 88

With the gonococcus, inflammatory changes appear in the affected glands approx 2-7 days after inoculation of the organisms. Wherever it occurs, gonococcal disease is characterized by an acute suppurative reaction w/inflammation largely confined to the superficial mucosa and underlying submucosa. Smears of the inflammatory exudate should disclose the intracellular gram-negative diplococcus, but absolute confirmation requires culture.

One it is within the tubes, and acute suppurative salpingitis occurs.

Front 89

89. What is the acute suppurative salpingitis?

Back 89

The tubal serosa becomes hyperemic and layered w/fibrin, the tubular fimbriae are similarly involved, the lumen fills w/purulent exudate that may leak out of the fimbriated end.

In days or weeks, the fimbriae may seal or become plastered against the ovary to create a salpingo-oophoritis. Collections of pus w/in the ovary and tube (pyosalpinx) may occur.

Also, adhesions of the tubal plica may produce glandlike spaces (follicular salpingitis).

Front 90

90. What is a hydrosalpinx?

Back 90

In the course of time, the infecting organisms may disappear, the pus undergoing proteolysis to a thin, serous fluid, to produce a hydrosalpinx or hydrosalpinx follicularis.

Front 91

91. What is the morphology of PID caused by staph, strep, and other puerperal invaders?

Back 91

Tends to have less exudation w/in the lumens of the tube and less involvement of the mucosa, w/a greater inflammatory response w/in the deeper layers.

The infection tends to spread thru the wall to involve the serosa and may often involve the broad ligaments, pelvic structures, and peritoneum. Bacteremia is a more freq complications of strep or staph PID than of gonococcal infections.

Front 92

92. What are the 4 complications of PID?

Back 92

1. Peritonitis
2. Intestinal obstruction due to adhesions between the small bowel and the pelvic organs
3. Bacteremia, which may produce endocarditis, meningitis, and suppurative arthritis
4. Infertility, one of the most commonly feared consequences of long-standing chronic PID.

Front 93

93. What is a bartholin cyst?

Back 93

Acute infection of the Bartholin gland produces an acute inflammation of the gland (adenitis) and may result in a Bartholin abscess. Bartholin cysts are relatively common, occur at all ages, and result from obstruction of the Bartholin duct, usually by a preceding infection.

These cysts may become large, up to 3-5 cm in diameter. The cyst is lined by either the transitional epithelium of the normal duct or squamous metaplasia.

The cysts produce pain and local discomfort; the cysts are either excised or opened permanently.

Front 94

94. What is vulvar vestibulitis?

Back 94

The vulvar vestibule is located in the posterior introitus at the entrance to the vagina and contains small glands in the submucosa (vestibualr glands).

A variety of disorders cause chronic pain in this area, known as vulvodynia. Chief among them are inflammation of the surface mucosa and vestibular glands associated w/a chronic, recurrent and exquisitely painful conditions known as vulvar vestibulitis. The inflammatory condition produces small ulcerations, which account for the extreme point tenderness in the vestibule.

Front 95

95. What is leukoplakia?

Back 95

A spectrum of inflammatory lesions of the vulva is characterized by opaque, white, scaly, plaquelike mucosal thickenings that produce vulvar discomfort and itching. B/c of their white appearance, they are termed leukoplakia.

This is a clinical descriptive term b/c white plaques may indicate a variety of benign, premalignant, or malignant lesions.

Front 96

96. Biopsy of a "leukoplakia" may reveal 1 of which 4 several conditions?

Back 96

1. Vitiligo (loss of pigment)
2. Inflammatory dermatoses (e.g., psoriasis, chronic dermatitis)
3. Vulvar intraepithelial neoplasia, Paget disease, or even invasive CA
4. A variety of alterations of unknown etiology

Front 97

97. What is lichen sclerosus and lichen simplex chronicus?

Back 97

Lichen sclerosus is a characteristic disorder manifested by subepithelial fibrosis. The skin becomes pale gray and parchment like, the labia are atrophies, and the introitus narrowed.

Lichen simplex chronicus is manifested by epithleial thickening (acanthosis) and hyperkeratosis.

These two forms may coexist in different areas of the same vulva, and the lesions are often multiple.

Front 98

98. What are the 4 cardinal histologic features of lichen sclerosus?

Back 98

1. Atrophy (thinning) of the epidermis, w/disappearance of the rete pegs
2. Hydropic degeneration of the basal cells
3. Replacement of the underlying dermis by dense collagenous fibrous tissue
4. A monoclonal bandlike lymphocytic infiltrate

Front 99

99. What are the clinical features of lichen sclerosus?

Back 99

It occurs in all age groups but is most common after menopause. The pathogenesis is unclear, but it has many features of an autoimmune disorder.

It is not recognized as a precancerous condition, but it has been associated w/genetic alterations and confers a greater than expected risk of subsequent CA.

Front 100

100. What is the pathogenesis of lichen simplex chronicus?

What are the characteristics?

Back 100

This is a non-specific condition resulting from rubbing or scratching the skin to relieve pruritus. The latter may result from known or unknown irritants.

It is characterized by ancanthosis of the vulvar squamous epithelium, freq w/hyperkeratosis. The epithelium is thickened and may show increased mitotic activity in both the basal and prickle cell layer, with variable infiltration of the dermis.

Front 101

101. Is lichen simplex chronicus premalignant?

Back 101

It is sometimes associated w/CA, but it is not, however, considered a significant cancer precursor unless there is coexisting epithelial atypia, in which case it is classified as a precancerous lesion (vulvar intraepithelial neoplasia).

Front 102

102. What is papillary hidradenoma?

Back 102

This benign tumor is identical in appearance to intraductal papillomas of the breast. It presents as a sharply circumscribed nodule, most commonly on the labia majora or interlabial folds, and may be confused clinically w/CA b/c of its tendency to ulcerate.

On histologic exam, hidradenomas consist of tubular ducts lined by a single or double layer of nonciliated columnar cells, with a layer of flattened "myoepithleial cells" underlying the epithelium. These myoepithelial cells are characteristic of sweat glands and sweat gland tumors.

Front 103

103. What is condyloma acuminatum?

Back 103

Condyloma acuminatus is a wartlike, verrucous lesion caused by HPV types 6 or 11. It occurs on the vulva, perineum, vagina, and (rarely) cervix. The lesions are frequently multiple and often coalesce.

Histologically, it consists of a sessile or branching (treelike) epithelial proliferation of stratified squamous epithelial cells, some of which may display perinuclear cytoplasmic clearing w/nuclear atypia (koilocytotic atypia). Flat or macular conylomas associated with other HPV types are also benign.

*They are a marker for sexually transmitted disease.

Front 104

104. What is vulva CA?

What are the two groups?

Back 104

CA of the vulva is an uncommon malignant neoplasm that mostly occurs in women older than 60. 85% of these malignant tumros are squamous cell CAs, the remainder being basal cell CA, melanomas, or adenocarcinomas.

It is divided into two groups:
1. Associated w/ cancer related HPV, and is preceded by an easily recognized precancerous change called vulvar intraepithelial neoplasia (VIN).
2. Those associated with squamous cell hyperplasia and lichen sclerosus.

Front 105

105. What is VIN?

Back 105

These vulvar intraepithelial neoplasias include lesions classified as CA in situ or Bowen disease.

VIN is characterized by nuclear atypia in the epithelial cells, increased mitoses, and lack of surface differentiation. It is analogous to high grade squamous intraepithelial lesions of the cervix.

These lesions usually present as white or pigmented plaques on the vulva.

Front 106

106. What is the pathogenesis of VINs?

Back 106

VIN is frequently multicentric, and 10-30% are associated w/another primary squamous neoplasm in the vagina or cervix. The association indicates a common etiologic agent.

90% of VIN cases and associated CA contain HPV DNA types 16, 18, and other high risk types.

Front 107

107. What is the pathogenesis of the second group of squamous cell CAs associated w/squamous cell hyperplasia and lichen sclerosus?

Back 107

Genetic alterations arise in lichen sclerosus or hyperplasia, leading directly to invasion, or by an intermediate step in which atypia develops w/in hyperplasia or lichen sclerosus, leading to an unusual form of VIN termed differentiated (simplex) VIN.

These tumors have also been associated w/increased accumulation of p53 protein.

Front 108

108. What is the morphology of HPV-associated vulvar squamous CA?

Back 108

These begin as classic VIN lesions, which present as discrete flesh-colored or pigmented, slightly raised lesions that may be hyperkeratotic.

On histologic exam, tumors associated with HPV or VIN freq exhibit invasive growth patterns that mimic intrapeithleial neoplasia. These patterns may be well-differentiated (warty) or poorly differentiated (basaloid).

Front 109

109. What are verrucous carcinomas and basal cell carcinomas of the vulva?

Back 109

Verrucous CAs are rare fungating tumors resembling condyloma acuminatus.

Basal cell CAs are identical to those seen in the skin.

Neither tumor is associated with HPV. Both tumors rarely metastasize and usually can be cured by wide excision.

Front 110

110. What is extramammary Paget disease?

Back 110

This curious and rare lesion of the vulva, and sometimes the perianal region, is similar in its skin manifestations to Paget disease of the breast. As a vulvular neoplasm, it manifests as a pruritic, red, crusted, sharply demarcated, maplike area, occurring usually on the labia majora. It may be accompanied by a palpable submucosal thickening or tumor.

Front 111

111. What is the morphology of extramammary Paget disease?

Back 111

The diagnostic microscopic feature of this lesion is the presence of *large tumor cells lying singly or in small clusters w/in the epidermis and its appendages. These cells are distinguished by a clear separation ("halo") from the surrounding epithelial cells and a finely granular cytoplasm containing mucopolysaccharide that stains with PAS, Alcian blue, or mucicarmine.*

Ultrastructurally, Paget cells display apocrine, eccrine, and keratinocyte differentiation and presumably arise from primitive epithelial progenitor cells.

Front 112

1112. What are the clinical features and prognosis of extramammary Paget disease?

Back 112

In contrast to Paget disease of the nipple, in which 100% of pts show an underlying ductal breast CA, vulvar lesions are most freq confined to the epidermis of the skin and adjacent hair follicles and sweat glands.

The prognosis of Paget disease is poor in the uncommon cases w/associated CA, but intraepidermal Paget disease may persist for many years, even decades, w/o the development of invasion. They are prone to recurrence.

Front 113

113. What is malignant melanoma of the vulva?

Back 113

Melanomas of the vulva are rare. Their peak incidence is in the 6th or 7th decade; they tend to have the same biologic and histologic characteristics as melanomas occurring elsewhere and are capable of widespread metastatic dissemination. The 5-yr survival rate is less than 32%, .

Prognosis is linked principally to depth of invasion, with greater than 60% mortality for lesions invading deeper than 1 mm.

B/c it is initially confined to the epithelium, melanoma may resemble Paget disease, both grossly and histologically. It can usually be differentiated by its uniform reactivity with antibodies to S100 protein, absence of reactivity w/antibodies to carcinoembryonic antigen, and lack of mucopoysaccharides, both of which are present in Paget disease.

Front 114

114. What are the congenital anomalies associated with the vagina?

Back 114

Atresia and total absence of the vagina are both extremely uncommon. The latter usually occurs only when there are severe malformations of the entire genital tract. Septate, or double, vagina is also an uncommon anomaly that arises from failure of total fusion of the mullerian ducts and accompanies double uterus (uterus didelphys).

Front 115

115. What are Gartner duct cysts?

Back 115

Gartner duct cysts are relatively common lesions found along the lateral walls of the vagina and derived from wolffian duct rests.

They are 1-2 cm fluid-filled cysts that occur submucosally.

Front 116

116. What are VIN and squamous cell CA of the vagina?

Back 116

Primary CA of the vagina in very uncommon - of these 95% are squamous cell CAs. Most are associated with HPV. The greatest risk factor is a previous CA of the cervix or vulva.

These tumors first come to the pts attention by the appearance of irregular spotting or the development of a frank vaginal discharge. At other times, they may remain totally silent and become clinically manifest only w/the onset of urinary or rectal fistulas.

Front 117

117. What is the morphology of VIN and squamous cell CA of the vagina?

Back 117

Most often, the tumor affects the upper posterior vagina, particularly along the posterior wall at the junction w/the ectocervix. It begins as a focus of epithleial thickening, often in association w/dysplastic changes, progressing to a plaquelike mass that extends centrifugally and invades, by direct continuity, the verix and perivaginal structures.

The lesions in the lower 2/3rds metastasize to the inguinal nodes, whereas upper lesions tend to involve the regional iliac nodes.

Front 118

118. What are adenocarcinomas of the vagina?

Back 118

They are rare but have received attention b/c of the increased freq of clear cell adenocarcinomas in young women whose mothers had been treated with diethylstillbestrol (DES) during pregnancy.

Front 119

119. What is the morphology of adenocarcinomas of the vagina?

Back 119

The tumors are most often located on the anterior wall of the vagina, usually in the upper third, and vary in size from 0.2 to 10 cm in greatest diameter. They are usually discovered between the ages of 15-20 years and are often composed of vacuolated, glycogen-containing cells.

*A probably precursor of the tumor is vaginal adenosis.

Front 120

120. What is vaginal adenosis?

Back 120

Vaginal adenosis is a condition in which glandular columnar epithelium of mullerian type either appears beneath the squamous epithelium or replaces it.

Adenosis presents clinically as red, granular foci contrasting w/the normal pale pink, opaque vaginal mucosa.

On microscopic exam, the glandular epithelium may be either mucus secreting, resembling endocervical mucosa, or tuboendometrial, often containing cilia.

Malignant transformation is extremely rare.

Front 121

121. What is the clinical course for vaginal carcinomas?

Back 121

B/c of its insidious, invasive growth, vaginal CA (both adenocarcinomas and squamous) is difficult to cure. Early detection by careful follow-up is mandatory in DES-exposed women. Surgery and irradiation have a 80% success rate.

Extension of cervical CA to the vagina is much more common than are primary malignant neoplasms of the vagina.

Front 122

122. What is an embryonal rhabdomyosarcoma (AKA sarcoma botryoides)?

Back 122

This is an uncommon vaginal tumor most freq found in infants and in children younger than 5 years. The tumors consists predominantly of malignant embryonal rhabdomyoblasts and is thus a type of rhabdomyosarcoma.

Conservative surgery, coupled w/chemo, appears to offer the best results in cases Dx sufficiently early.

Front 123

123. What is the morphology of an embryonal rhabdomyosarcoma?

Back 123

These tumors tend to grow as polypoid, rounded, bulky masses that sometimes fill and project out of the vagina; they have the appearance and consistency of grape-like clusters.

On histologic exam, the tumor cells are small and have oval nuclei, with small protrusions or cytoplasm from one end, so they resemble a tennis racket.

Front 124

124. What causes acute and chronic cervicitis?

Back 124

Cervicitis may be cauased either by specific infections, such as gonococci, chlamydia, Trichomonas vaginalis, Candidia, and Mycoplasma, or by endogenous vaginal aerobes and anaerobes, including streptococci, enterococci, E. coli, and staph (nonspecific cervicitis).

Front 125

125. What is the definition of chronic cervicitis?

Back 125

There is a process of transformation from a columnar to a squamous lining. As the columnar surface is obliterated by the squamous epithelium overgrowth, there is accumulation of mucus in deeper crypts (glands) to form mucous (nabothian) cysts.

This process is invariably associated w/an inflammatory infiltrate composed of a mixture of polymorphonuclear leukocytes and mononuclear cells, and if the inflammation is severe, it may be associated with loss of the epithelial lining and epithelial repair.

Front 126

126. When is acute cervicitis encountered?

Back 126

Acute cervicitis is most commonly encountered postpartum and is characterized by acute infiltration of neutrophils beneath the lining mucosa.

Front 127

127. What is the morphology of acute and chronic cervicitis?

Back 127

There is epithelial spongiosis (intercellular edema), submucosal edema, and a combo of epithelial and stromal changes.

Acute cervicitis is noted by acute inflammatory cell, erosion, and reactive or reparative epithelial change.

Chronic cervicitis is notes with inflammation, usually mononuclear, w/lymphocytes, macrophages, and plasma cells. Necrosis and granulation tissue may also be present.

HSV is most strongly associated w/epithelial ulcers and a lymphocytic infiltrate, C. trachomatis w/lymphoid germinal centers and a prominent plasmacytic infiltrate, and epithelial spongiosis is associated w/T. vaginalis infection.

Front 128

128. What are endocervical polyps?

Back 128

Endocervical polyps are relatively innocuous, inflammatory tumors that occur in 2-5% of adult women.

The major significance of polyps lies in their production of irregular vaginal "spotting" or bleeding that arouses suspicion of some more ominous lesion. Most polyps arise w/in the endocervical canal and vary from small and sessile to large, 5 cm masses that may protrude thru the cervical os.

All are soft, almost mucoid, and are composed of a loose fibromyxomatous stroma harboring dilated, mucus-secreting endocervical glands, often accompanied by inflammation and squamous metaplasia.

Front 129

129. What is the pathogenesis of cervical CA?

Back 129

Cervical CA is is associated with HPV. HPV is currently considered to be the most important agent in cervical oncogenesis. Other risk factors are associated with:
1. Early age at first intercourse
2. Multiple sexual partners
3. Increased parity
4. A mall partner w/multiple previosu partners
5. The presence of a CA-associated HPV
6. The persistn detection of a high risk HPV
7. Certain HLA and viral subtypes
8. Exposure to oral contraceptives and nicotine
9. Genital infections (chlamydia)

Front 130

130. What is the evidence for linking HPV to cervical CA?

Back 130

1. HPV DNA is detected in over 95% of cervical CAs
2. High risk types are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68
3. Viral (E6 and E7) genes of high risk HPVs can disrupt cell cycle via binding to RB w/up-regulation of Cyclin E and p16INK4; interrupt cell death by binding to p53
4. The certain chromosome abnormalities have been associated with cancer containing specific (HPV-16) HPVs.
5. Recent data indicate that vaccines directed against HPV can prevent infection and development of precancerous disorders.

Front 131

131. What are some other factors in cervical CA?

Back 131

The evidence does not implicate HPV as the only factor. A high % of young women are infected w/one or more HPV types and only a few develop CA.

Other cocarcinogens, the immune status of the individual, nutrition, and other factors influence whether the HPV infection remains subclinical, turns into a precancer, or eventually progresses to CA.

Front 132

132. What is cervical intraepithelial neoplasia (CIN)?

Back 132

This lesion may exist in the noninvasive stage for as long as 20 years and shed abnormal cells that can be detected on cytologic exam.

Progression from CIN to cancer takes on an average over 12 years and the risk of progression increases w/higher grade CINs (CIN III or carcinoma in situ). The avg age of women w/CIN is 25-30 and of women w/cervical CA, 40-45.

*Risk of progression to malignancy is proportional to the grade of CIN and type of HPV, but the rates of progression are not uniform.

Front 133

133. What is the morphology of CIN I?

Back 133

CIN I are lesiosn often indistinguishable from condylomata acuminata and may be either raised or macular in appearance.

These lesions typically exhibit nuclear enlargement and hyperchromasia in the superficial epithelial cells. The nuclear changes may be accompanied by cytoplasmic halos with few alterations in the lower epithelial cells.

*Raised lesions (acuminatum) often contain low risk HPVs. Flat CIN usually contain high risk HPVs.

Front 134

134. What is the morphology of CIN II?

Back 134

The next change consists of the appearance of atypical cells in the lower layers of the squamous epithelium but nonetheless with persistent (but abnormal) differentiation toward the prickle and keratinizing cell layers.

The atypical cells show changes in nucleo-cytoplasmic ration; variation in nuclear size; loss of polarity; increased mitotic figures; and hyperchromasia. In other words, they take on some of the characteristics of malignant cells.

These lesions have been associated strongly with high-risk HPV types.

Front 135

135. What is the morphology of CIN III?

Back 135

As the lesion evolves, there is progressive loss of differentiation accompanied by greater atypia in more layers of the epithelium, until it is totally replaced by immature atypical cells, exhibiting no surface differentiation (CIN III). This is carcinoma in situ.

Front 136

136. Do all lesions begins as CIN I?

Back 136

Not all lesions begin as condylomata or as CIN I, and they may enter at any point in the sequence, depending on the type of HPV and other host factors.

*The risk of CA is conferred only in part by HPV type and may depend on both host-virus interactions and environmental factors to bring about the evolution of a precancer.

Front 137

137. What is the prevalence of squamous cell CA of the cervix?

Back 137

Squamous cell CA may occur at any age from the second decade of life to senility.

The peak incidence is occurring at an increasingly younger age - 40-45 years for invasive CA, and about 30 years for high-grade precancers.

Front 138

138. What is the morphology of invasive cervical CA?

Back 138

It exists in three gross morphologic patterns: exophytic or fungating, ulcerating, and infiltrative.

During pap smar, the most common variant obvious to the naked eye is the fugnating tumor, which produces and obviously neoplastic mass that projects above the surrounding mucosa.

On histologic exam, about 95% of squamous CAs are composed of relatively large cells, either keratinizing (well-differentiated) or nonkeratinizing (moderately differentiated) patterns. A small subset of tumors are poorly differentiated or more rarely, small cell undifferentiated CAs (neuroendocrine or oat cell CAs). The latter closely resemble oat cell CAs of the lung and have an unusually poor prognosis owing to early spread by lymphatics.

Front 139

139. What are stages 0-1 in cervical CA?

Back 139

Stage 0: CA in situ (CIN III)

Stage 1: Ca confined to the cervix
1a: Preclinical CA, Dx via microscopy
1a1: Stromal invasion no greater than 3 mm and no wider than 7 mm (microinvasive CA)
1a2: Max depth of invasion of stroma greater than 3 mm and no greater than 5 mm; horizontal invasion not more than 7 mm
1b: Histologically invasive CA confined to the cervix and greater than stage 1a2.

Front 140

140. What are stages 2-4 in cervical CA?

Back 140

II: CA extends beyond the cervix but not onto the pelvic wall. Ca involves the vagina but not the lower third.

III: CA has extended onto pelvic wall. On rectal exam, there is no cancer-free space btwn the tumor and the pelvic wall. The tumor involves the lower third of the vagina.

IV: CA has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. This stages includes those with metastatic dissemination.

Front 141

141. What are the variants of cervical CAs?

Back 141

10-25% of cervical CAs are adenocarcinomas, adenosquamous CAs, undifferentiated CAs, or other rare histologic types.

The adenocarcinomas presumably arise in the endocervical glands and are often preceded by a precancer termed adenocarcinoma in situ.

Once invasion develops, adenocarcinomas appear grossly and behave like the squamous cell lesions, with the exception of association with HPV type 18.

Front 142

142. Why are adenosquamous CAs important?

Back 142

They have mixed glandular and squamous patterns and are through to arise from the multipotent reserve cells in the basal layers of the endocervical epithelium.

*They tend to have a less favorable prognosis than does squamous cell CA of similar stage.

Front 143

143. What do CIN lesions look like on colposcopic exam?

Back 143

They appear as white patches on the cervix after application of acetic acid.

In addition, distinct vascular mosaic or punctuation patterns can be observed

Front 144

144. In biopsies, what are the immunohistochemical identification markers for cervical cancer??

Back 144

There is increased expression of host cell biomarkers (i.e. p16INK4, cyclin E, and Ki-67).

These markers are expressed in a greater proportion of cells in precancerous lesions and will frequently distinguish these from non-neoplastic epithelial changes.

Front 145

145. Most patients with stage IV CA die as a consequence of...?

Back 145

Local extension of the tumor (e.g., into and about the urinary bladder and ureters, leading to ureteral obstruction, pyelonephritis, and uremia) rather than distant metastases.

Front 146

146. What are functional endometrial disorders (dysfunctional uterine bleeding)?

Back 146

The most common gynecologic problem in women is the occurrence of excessive bleeding during or between menstrual periods.

The causes of abnormal bleeding from the uterus are many and vary among women of different age groups. In some instances, bleeding is the result of a well-defined organic abnormality, such as chronic endometritis, submucosal leiomyomas, endometrial polyp, or endometrial neoplasms.

However, the largest group is due to functional endometrial disorders.

Front 147

147. What is the cause of dysfunctional bleeding in most instances?

Back 147

In most instances, dysfunctional bleeding is due to the occurrence of an anovulatory cycle, which results in excessive and prolonged estrogenic stimulation w/o the development of the progestational phase that regularly follows ovulation.

Front 148

148. Less commonly, lack of ovulation is the result of what three things?

Back 148

1. An endocrine disorder, i.e. thyroid disease, adrenal disease, or pituitary tumors
2. A primary lesion of the ovary, such as a functioning ovarian tumor (granulose-theca cell tumors) or polycystic ovaries
3. A generalized metabolic disturbance, such as marked obesity, severe malnutrition, or any chronic systemic disease.

Front 149

149. Failure of ovulation results in...?

Back 149

Prolonged, excessive endometrial stimulation by estrogens. Under these circumstances, the endometrial glands undergo mild architectural changes, including cystic dilation.

Unscheduled breakdown of the stroma may also occur (anovulatory menstruation) with no evidence of secretory activity.

Front 150

150. What is an inadequate luteal phase

Back 150

This term refers to the occurrence of inadequate corpus luteum function and low progesterone output, with an irregular ovulatory cycle. The condition manifests clinically as infertility, with either increased bleeding or amenorrhea.

Endomeditral biopsy performed at an estimated postovulatory date shows secretory endometrium, which, however, lags in its secretory characteristics w/respect to the expected date.

Front 151

151. What type of changes do oral contraceptives cause in the endometrium?

Back 151

A common response pattern is a discordant appearance btwn glands and stroma, usually w/inactive glands amid a stroma showing large cells with abundant cytoplasm reminiscent of the decidua of pregnancy.

When such therapy is discontinued, the endometrium reverts to normal. All these changes have been minimized w/the newer low-dose contraceptives.

Front 152

152. What are the changes that occur to the endometrium during menopause and after?

Back 152

B/c the menopause is characterized by anovulatory cycles, architectural alterations in the endometrial glands may be present transiently, followed by ovarian failure and atrophy of the endometrium.

A component of anovulatory cycles includes mild hyperplasias with cystic dilation of glands. If this is followed by complete ovarian atrophy and loss of stimulus, the cystic dilation may remain, while the ovarian stroma and gland epithelium undergo atrophy.

In this case, so-called cystic atrophy results.

Front 153

153. Why is the endometrium normally resistant to infections?

Back 153

The endometrium and myometrium are relatively resistant to infections, primarily b/c the endocervix normally forms a barrier to ascending infection.

Acute inflammation of the endometrium is uncommon and limited to bacterial infections that arise after delivery or miscarriage. Retained products of conception are the usual predisposing influence, causative agents including group A hemolytic streptococci, staph, and other bacteria.

Front 154

154. In what 4 settings does chronic endometritis occur?

Back 154

1. In pts suffering from chronic PID
2. In pts w/postpartal or postabortal endometrial cavities, usually due to retained gestational tissue
3. In pts w/intrauterine contraceptive devices
4. In pts w/tuberculosis, either from miliary spread, or more commonly, from drainage of tuberculous salpingitis.

In about 15% of cases, no such primary cause is obvious, yet plasma cells are seen together w/macrophages and lymphocytes. Some women w/this so-called non-specific endometritis have gynecologic complaints. *Chlamydia may be involved.

Front 155

155. What is endometriosis?

In what six locations does it occur?

Back 155

Endometriosis is the term used to describe the presence of endometrial glands or stroma in abnormal locations outside the uterus.

It occurs in the following sites (in descending order of freq):
1. Ovaries
2. Uterine ligaments
3. Rectovaginal septum
4. Pelvic peritoneum
5. Laparotomy scars
6. Rarely in the umbilicus, vagina, vulva, or appendix

Front 156

156. What is adenomyosis?

Back 156

A closely related disorder, adenomyosis, is defined as the presence of endometrial tissue in the uterine wall (myometrium). It occurs in up to 20% of uteri.

On microscopic exam, irregular nests of endometrial stroma, w/or w/o glands, are arranged w/in the myometrium, separated from the basalis by at least 2-3 mm.

Front 157

157. What is the most important consequence of adenomyosis in some pts?

Back 157

In some pts, the most important consequence of adenomyosis is shedding of the endometrium during the menstrual cycle.

Hemorrhage w/in these small adenomyotic nests results in menorrhagia, colicky dysmenorrhea, dyspareunia, and pelvic pain, particularly during the premenstrual period.

Front 158

158. Why is endometriosis a particularly important clinical condition?

Back 158

It often causes infertility, dysmenorrhea, pelvic pain, and other problems.

The disorder is principally a disease of women in active reproductive life, most often in the third and fourth decades, and afflicts approx 10% of women.

Front 159

159. What are 3 theories in the pathogenesis of endometriosis?

Back 159

1. The regurgitation/implantation theory - retrograde menstruation thru the fallopian tubes occurs and spreads endometrial tissue.

2. The metaplastic theory - endometrium arises from coelomic epithelium, from which the mullerian ducts and the endometrium itself originate.

3. The vascular or lymphatic dissemination theory - dissemination thru pelvic veins and lymphatics would explain the presence of endometriotic lesions in the lungs or lymph nodes.

Front 160

160. What is the genetic basis behind endometriosis?

Back 160

Based on the finding of aromatase P450 in the endometriotic tissue but not in normal endometrium, it has been suggested that the endometriotic tissue possesses the capacity to produce its own estrogens via this enzyme.

Front 161

161. What is the morphology of endometriosis?

Back 161

The foci of endometrium respond to both extrinsic cyclic (ovarian) and intrinsic homronal stimulation w/periodic bleeding. This produces nodules w/a red-blue to yellow-brown appearance on or beneath the serosal surfaces.

When the disease is extensive, organizing hemorrhage causes extensive fibrous adhesions btwn tubes, ovaries, and other structures and obliteration of the pouch of Douglas. The ovaries may become markedly distorted by large cystic masses filled with brown blood debris (chocolate cysts).

Front 162

162. When is the histologic Dx of endometriosis sufficient?

Back 162

When the endometrial stroma is present, or in its absence, mullerian epithelium with subjacent hemosiderin pigment.

Front 163

163. What is the clinical course of endometriosis?

Back 163

Clinical signs and symptoms usually consist of severe dysmenorrhea, dysparenuina, and pelvic pain due to the intrapelvic bleeding and periuterine adhesions. Pain on defecation indicates rectal wall involvement, and dysuria reflects involvement of the serosa of the bladder.

Intestinal disturbances may appear when the small intestine is affected.

Menstrual irregularities are common, and infertility is the presenting complaint in 30-40% of women.

Front 164

164. What are endometrial polyps?

Back 164

Endometrial polyps are sessile tumors composed of endometrial glands and stroma. They may be associated w/hyperestrogennism or tamoxifen therapy.

These polyps are usually benign but occasionally may harbor endometrial hyperplasia or cancer.

Stromal cells in the polyps are clonal, w/chromosome 6p21 rearrangements.

Front 165

165. What is endometrial hyperplasia (endometrial intraepithelial neoplasia)?

Back 165

Endometrial hyperplasia is another cause of abnormal bleeding that differs from typical anovulation by an increased gland to stroma ratio and abnormalities in epithelial growth relative to normal endometrium.

*Numerous studies have largely confirmed the malignant potential of certain endometrial hyperplasias and the concept of a continuum of glandular atypia and in some cases, CA.

Front 166

166. What is the pathogenesis of endometrial hyperplasia?

Back 166

Endometrial hyperplasia is linked to prolonged estrogen stimulation of the endometrium by anovulation or increased estrogen production.

Conditions promoting hyperplasia include menopause, polycystic ovarian disease, functioning granulosa cell tumors of the ovary

Front 167

167. What are the genetic factors in the development of endometrial hyperplasia and related CAs?

Back 167

Inactivation of the PTEN tumor suppressor gene through deletion and/or activation.

Its most important function is a lipid phosphatase blocking Akt phosphorylation in the P13K pathway.

Front 168

168. What is the morphology of endometrial hyperplasia?

Back 168

Endometrial hyperplasia has traditionally been divided into lower grade (simple) and higher grade (atypical) subgroups. Currently, the lower grade hyperplasias include both anovulatory epithelium and, less commonly, subtle endometrial intraepithelial neoplasms (EIN).

In contrast, higher-grade hyperplasias typically have the morphologic features (gland crowding and cytologic atypia) and genetic characteristics (PTEN mutations) of intraepithelial neoplasia.

Front 169

169. What is the morphology of simple non-atypical hyperplasias?

Back 169

These are AKA cystic or mild hyperplasias and are characterized by architectural changes in glands of various sizes, producing irregularity in gland shape, w/cystic alterations. The epithelial growth pattern and cytology are similar to those of proliferative endometrium, although mitoses are not as prominent.

These lesions uncommonly progress to adenocarcinoma and largely reflect a response to persistent estrogen stimulation. These simple cystic hyperplasias freq evolve into cystic atrophy in which both the epithelium and stroma become atrophic.

Front 170

170. What is the morphology of complex atypical hyperplasias (EIN)?

Back 170

Complex atypical hyperplasias exhibit an increase in the number and size of endometrial glands, w/gland crowing, enlargement, and irregular shape.

The glands remain distinct and non-confluent, characteristic of an intraepithelial neoplasm. Mitotic figures are common. Predictably, in the most severe forms, cytologic and architectural atypia may border on adenocarcinoma.

Front 171

171. What is carcinoma of the endometrium?

Back 171

Endometrial CA is the most common cancer of the female genital tract and accoutns for 7% of all invasive CA in women.

They mainly arise in postmenopausal women, causing abnormal bleeding. This permits early detection and cure at an early stage.

Front 172

172. Endometrial CA is more common in which 4 populations?

Back 172

1. Obesity
2. DM
3. Hypertension
4. Infertility

Infrequently, both endometrial and breast CA arise in the same patient.

Front 173

173. What is the pathogenesis of endometrial CA?

Back 173

To general groups can be identified. The first develops on a background of prolonged estrogen stimulation and endometrial hyperplasia.

The second subset less commonly exhibits the stigmata of hyperestrinism or preexisting hyperplasia, and acquires the disease at a somewhat older average age.

Front 174

174. What is the link between hyperplasia and CA of the endometrium?

7 of them... shit!

Back 174

1. Both hyperplasia and CA are also linked w/obesity and anovulatory cycles
2. Women w/ovarian estrogen-secreting tumors have a higher risk of endometrial CA
3. Endometrial CA is rare in women w/ovarian agenesis and in those castrated early in life
4. Estrogen replacement therapy is associated w/increased risk
5. Prolonged administration of DES may produce endometrial polyps, hyperplasia, and CA
6. In postmenopausal women, there is greater synthesis of estrogens in body fat from adrenal and ovarian androgen precursors
7. Inactivation of the PTEN gene is common to endometrial hyperplasia and CA, as is microsatellite instability.

Front 175

175. What are the characteristics of endometrial CAs that are associated w/hyperplasia?

Back 175

These tend to be well differentiated, mimicking normal endometrial glands (endometrioid) in histologic appearance, or to display altered differentiation (mucinous, tubal, squamous differentiation). This latter group of tumors is associated w/a more favorable prognosis than tumors w/o hyperplasia.

These tumors generally do not tend to spread to the peritoneal surfaces.

Front 176

176. What are the characteristics of endometrial CAs that are in the second subset (serous subtypes)?

Back 176

In this group, tumors are generally more poorly differentiated, including tumors that resemble subtypes of ovarian CAs (serous CAs).

Overall, these tumors have a poorer prognosis than estrogen-related cancers do.

Front 177

177. What are the genetic differences in serous subtypes of endometrial CAs?

Back 177

In contrast to endometroid tumors, *serous subtypes infrequently display microsatellite instability and are linked to mutation of p53.*

They presumably begin as surface epithelial neoplasms that extend into adjacent gland structures and later invade endometrial stroma.

Front 178

178. What is the morphology of endometrial CA?

Back 178

In gross appearance, endometrial CA presents either as a localized polypoid tumor or as a diffuse tumor involving the entire endometrial surface. Spread generally occurs via direct myometrial invasion w/eventual extension to the periuterine structures by direct continuity.

On histologic exam, most are adenocarcinomas characterized by more or less well-defined gland patterns closely resembling normal endometrial epithelium.

Front 179

179. Where do endometrial CAs spread?

Back 179

Spread into the broad ligaments may create a clinically palpable mass. Dissemination to the regional lymph nodes eventually occurs, and in the late stages, the tumor may metastasize to the lungs, liver, bones, and other organs.

Front 180

180. What are papillary serous carcinomas and clear cell CAs?

Back 180

These tumor types are managed as grade 3 carcinomas irrespective of histologic pattern.

***Serous tumors in particular are a highly aggressive form of uterine CA, 80% of which harbor p53 mutations and accumulate p53 protein.

Front 181

181. What are the 4 stages of endometrial CA?

Back 181

Stage I: CA is confined to the corpus uteri itself

Stage II: CA has involved the corpus and the cervix

Stage III: CA has extended outside the uterus but not outside the true pelvis

Stage IV: CA has extended outside the true pelvis or has obviously involved the mucosa of the bladder or the rectum.

Front 182

182. What are the 3 grades of endometrial CA?

Back 182

G1: Well differentiated adenocarcinoma

G2: Differentiated adenocarcinoma w/partly solid areas

G3: Predominantly solid or entirely undifferentiated CA. Serous and clear cell CAs are automatically classified as grade 3.

Front 183

183. What are the clinical features of endometrial CA?

Back 183

The patient usually presents w/abnormal bleeding or an abnormal Pap smear.

The prognosis depends on the state of the disease and is excellent in pts in whom the CA is confined to the corpus uteri itself. However, serous tumors, like their counterparts in the ovary, can spread quickly, even when noninvasive.

Front 184

184. What are carcinosarcomas?

Back 184

Carcinosarcomas consist of endometrial adenocarcinoams in which malignant stromal differentiation takes place. The stroma tends to differentiate into a variety of malignant mesodermal components, including muscle, cartilage, and even osteoid. The epithelial and stromal components are presumably derived from the same cell.

These occur in perimenopausal women and manifest, similarly to adenocarcinoma, with postmenopausal bleeding. Many affected pts give a history of previous radiation therapy.

*Carcinosarcomas usually metastasize as adenocarcinomas.

Front 185

185. What is the morphology of carcinosarcomas?

Back 185

In gross appearance, such tumors are somewhat more fleshy than adenocarcinomas, may be bulky and polypoid, and sometimes protrude thru the cervical os.

On histology, the tumors consist of adenocarcinoma mixed with the stromal (sarcoma) elements; alternatively, the tumor may contain two distinct and separate epithelial and mesenchymal components. Sarcomatous components may mimic extrauterine tissues (i.e. striated muscle cells, cartilage, adipose tissue, and bone).

Front 186

186. What are adenosarcomas?

What is the Dx based upon?

Back 186

Adenosarcomas present most commonly as large broad-based endometrial polypoid growth, and may prolapse thru the cervical os.

The Dx is based on malignant appearing stroma, which coexists w/benign but abnormally shaped endometrial glands.

Front 187

187. What are the clinical features of adenosarcomas?

What is the principal diagnostic dilemma?

Back 187

These tumors predominate in women between the 4th and 5th decades and are generally of low grade malignancy; recurrences develop in 25% and are nearly always confined to the pelvis.

The principal diagnostic dilemma is distinguishing these tumors from large benign polyps. The distinction is important b/c oophorectomy is typically performed in cases of adenosarcoma since they are estrogen sensitive.

Front 188

188. What are stromal tumors?

Back 188

The endometrial stroma occasionally gives rise to neoplasms that may resemble normal stromal cells. Similar to most neoplasms, they may be well or poorly differentiated.

They are divided into two categories:
1. Benign stromal nodules
2. Endometrial stromal sarcomas

Front 189

189. What is the morphology of stromal nodules?

Back 189

Stroma nodules are a well circumscribed aggregate of endometrial stromal cells in the myometrium that does not penetrate the myometrium and is of little consequence.

Front 190

190. What is the morphology of stromal sarcomas?

Back 190

Stromal sarcomas consist of neoplastic endometrial stroma lying between muscle bundles of the myometrium and is distinguished from stromal nodules by either diffuse infiltration of myometrial tissue or the penetration of lymphatic channels.

Front 191

191. What are the clinical features of stromal tumors?

Back 191

About 1/2 of these tumors recur, with relapse rates of 36% to over 80% for State I and Stage II/IV, respectively; relapse cannot be predicted.

Distant metastases, which sometimes may occur decades after initial Dx, and death from metastatic tumor occur in about 15% of cases. Five year survival rate is about 50%.

Front 192

192. What are the genetics in the pathogenesis of stromal tumors?

Back 192

Recent studies indicate that a recurrent chromosomal translocation, t(7;17)(p15;q21), occurs in endometrial stromal sarcoma.

As a consequence of this translocation, the fusion of the two previously unknown genes, JAZF1 and JJAZ1 occurs, with production of a fusion transcript and protein.

Front 193

193. What are leiomyomas?

Back 193

Uterine leiomyomas (aka fibroids) are the most common tumor in humans. These tumors are present in about 75% of females of reproductive age, and each uterus harbors an avg of 6.5 tumors.

Each uterine leiomyoma is a unique clonal neoplasm. Most have normal karyotypes, but approx 40% have a simple chromosomal abnormality.

There are six cytogenetic groups that have been recognized; this suggests that more than one genetic mechanism can lead to leiomyoma growth.

Front 194

194. What is the morphology of leiomyomas?

Back 194

Leiomyomas are sharply circumscribed, discrete, round, firm, gray-white tumors varying in size from small, barely visible nodules to massive tumors that fill the pelvis. Except in rare instances, they are found w/in the myometrium of the corpus.

Whatever their size, the characteristic whorled pattern of smooth muscle bundles on cut section usually makes these lesions readily identifiable on gross inspection. Large tumors may develop areas of yellow-brown to red softening (red degeneration).

Front 195

195. What are the histologic characteristics of leiomyomas?

Back 195

On histo exam, the leiomyoma is composed of *whorled bundles of smooth muscle cells.*

Usually, the muscle cells are uniform in size and shape and have the characteristic oval nucleus and long, slender bipolar cytoplasmic processes. Mitotic figures are scarce.

Front 196

196. What are the variant forms of leiomyomas?

Back 196

Benign variants include atypical or bizarre (symplastic) tumors w/nuclear atypia and giant cells and cellular leiomyomas. Both have low mitotic index.

An extremely rare variant, benign metastasizing leiomyoma, consists of a uterine tumor that extends into vessels and migrates to other sites, most commonly the lung.

Another variant, disseminated peritoneal leiomyomatosis, presents as multiple small nodules on the peritoneum.

Front 197

197. What are the clinical features of leiomyomas?

Back 197

They may be asymptomatic, but the most important symptoms are produced by submucosal leiomyomas (abnormal bleeding), compression of the bladder, and sudden pain if disruption of blood supply occurs, and impaired fertility.

Myomas in pregnant women increase the freq of spontaneous abortion, fetal malpresentation, uterine intertia, and postpartum hemorrhage.

Malignant transformation (leiomyosarcoma) within a leiomyoma is rare.

Front 198

198. What are leiomyosarcomas?

Back 198

These uncommon malignant neoplasms arise de novo directly from the myometrium or endometrial stroma undergoing smooth muscle differentiation. In contrast to leiomyomas, leiomyosarcomas have karyotypes that are complex and more random.

These include deletions identified on a number of chromosomes that are not seen in benign tumors.

Front 199

199. What is the morphology of leiomyosarcomas?

How are they differentiated from benign leiomyomas?

Back 199

Leiomyosarcomas grow w/in the uterus in two patterns: bulky fleshy masses that invade the uterine wall, or polypoid masses that project into the uterine lumen.

On histologic exam, they contain a wide range of atypia.

They are differentiated from benign leiomyomas by the presence of:
1. > 10 mitoses per 10 HPF, with or w/o cellular atypia
2. Between 5 and 10 mitoses per 10 HPF with cellular atypia.

Front 200

200. What are the clinical features of leiomyosarcomas?

Back 200

Leiomyosarcomas are equally common before and after menopause, w/a peak incidence at 40-60.

These tumors disseminate throughout the abdominal cavity and aggressively metastasize.

The 5-year survival rate avg is 40%.