Pbl Exam 7 Case 3-2

Front 1

1. What is trichomonas vaginalis?

Back 1

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 2

2. What is pelvic inflammatory disease (PID)?

Back 2

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 3

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

Back 3

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 4

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

Back 4

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 5

5. What is the morphology of gonococcal PID?

Back 5

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 6

6. What is the acute suppurative salpingitis?

Back 6

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 7

7. What is a hydrosalpinx?

Back 7

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 8

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

Back 8

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 9

9. What are the four complications of PID?

Back 9

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 10

10. What is a bartholin cyst?

Back 10

Acutgte 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 11

11. What is vulvar vestibulitis?

Back 11

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 12

12. What is leukoplakia?

Back 12

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 13

13. Biopsy of a "leukoplakia" may reveal one of what four several conditions?

Back 13

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 14

14. What is lichen sclerosus and lichen simplex chronicus?

Back 14

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 15

15. What are the four cardinal histologic features of lichen sclerosus?

Back 15

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 16

16. What are the clinical features of lichen sclerosus?

Back 16

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 17

17. What is the pathogenesis of lichen simplex chronicus?

What are the characteristics?

Back 17

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 18

18. Is lichen simplex chronicus premalignant?

Back 18

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 19

19. What is papillary hidradenoma?

Back 19

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 20

20. What is condyloma acuminatum?

Back 20

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 21

21. What is vulva CA?

What are the two groups?

Back 21

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 22

22. What is VIN?

Back 22

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 23

23. What is the pathogenesis of VINs?

Back 23

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 24

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

Back 24

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 25

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

Back 25

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 26

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

Back 26

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 27

27. What is extramammary Paget disease?

Back 27

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 28

28. What is the morphology of extramammary Paget disease?

Back 28

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 29

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

Back 29

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 30

30. What is malignant melanoma of the vulva?

Back 30

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 31

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

Back 31

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 32

32. What are Gartner duct cysts?

Back 32

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 33

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

Back 33

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 34

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

Back 34

Most oftne, 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 35

35. What are adenocarcinomas of the vagina?

Back 35

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 36

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

Back 36

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 37

37. What is vaginal adenosis?

Back 37

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 38

38. What is the clinical course for vaginal carcinomas?

Back 38

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 39

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

Back 39

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 40

40. What is the morphology of an embryonal rhabdomyosarcoma?

Back 40

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 41

41. What causes acute and chronic cervicitis?

Back 41

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 straph (nonspecific cervicitis).

Front 42

42. What is the definition of chronic cervicitis?

Back 42

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 43

43. When is acute cervicitis encountered?

Back 43

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

Front 44

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

Back 44

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 45

45. What are endocervical polyps?

Back 45

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 46

46. What is the pathogenesis of cervical CA?

Back 46

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 47

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

Back 47

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 48

48. What are some other factors in cervical CA?

Back 48

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 49

49. What is cervical intraepithelial neoplasia (CIN)?

Back 49

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 50

50. What is the morphology of CIN I?

Back 50

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 51

51. What is the morphology of CIN II?

Back 51

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 52

52. What is the morphology of CIN III?

Back 52

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 53

53. Do all lesions begins as CIN I?

Back 53

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 54

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

Back 54

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 55

55. What is the morphology of invasive cervical CA?

Back 55

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 56

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

Back 56

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 57

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

Back 57

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 58

58. What are the variants of cervical CAs?

Back 58

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 59

59. Why are adenosquamous CAs important?

Back 59

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 60

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

Back 60

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

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

Front 61

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

Back 61

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 62

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

Back 62

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 63

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

Back 63

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 64

64. What is cause of dysfunctional bleeding in most instances?

Back 64

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 65

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

Back 65

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 66

66. Failure of ovulation results in...?

Back 66

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 67

67. What is an inadequate luteal phase?

Back 67

This term refers to the occurrence of inadequate coorpus 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 68

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

Back 68

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 69

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

Back 69

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 70

70. Why is the endometrium normally resistant to infections?

Back 70

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 71

71. In what four settings does chronic endometritis occur?

Back 71

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 72

72. What is endometriosis?

In what six locations does it occur?

Back 72

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 73

73. What is adenomyosis?

Back 73

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 74

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

Back 74

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 75

75. Why is endometriosis a particularly important clinical condition?

Back 75

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 76

76. What are three theories in the pathogenesis of endometriosis?

Back 76

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 77

77. What is the genetic basis behind endometriosis?

Back 77

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 78

78. What is the morphology of endometriosis?

Back 78

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 79

79. When is the histologic Dx of endometriosis sufficient?

Back 79

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

Front 80

80. What is the clinical course of endometriosis?

Back 80

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 81

81. What are endometrial polyps?

Back 81

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 82

82. What is endometrial hyperplasia (endoemtrial intraepithelial neoplasia)?

Back 82

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 83

83. What is the pathogenesis of endometrial hyperplasia?

Back 83

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 84

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

Back 84

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 85

85. What is the morphology of endometrial hyperplasia?

Back 85

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 86

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

Back 86

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 87

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

Back 87

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 88

88. What is carcinoma of the endometrium?

Back 88

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 89

89. Endometrial CA is more common in which four populations?

Back 89

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

Infrequently, both endometrial and breast CA arise int eh same patient.

Front 90

90. What is the pathogenesis of endometrial CA?

Back 90

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 91

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

7 of them... shit!

Back 91

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 92

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

Back 92

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 93

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

Back 93

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 94

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

Back 94

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 95

95. What is the morphology of endometrial CA?

Back 95

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 96

96. Where do endometrial CAs spread?

Back 96

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 he lungs, liver, bones, and other organs.

Front 97

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

Back 97

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 98

98. What are the four stages of endometrial CA?

Back 98

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 99

99. What are the three grades of endometrial CA?

Back 99

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 100

100.What are the clinical features of endometrial CA?

Back 100

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 101

101. What are carcinosarcomas?

Back 101

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 102

102. What is the morphology of carcinosarcomas?

Back 102

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 103

103. What are adenosarcomas?

What is the Dx based upon?

Back 103

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 104

104. What are the clinical features of adenosarcomas?

What is the principal diagnostic dilemma?

Back 104

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 105

105. What are stromal tumors?

Back 105

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 106

106. What is the morphology of stromal nodules?

Back 106

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 107

107. What is the morphology of stromal sarcomas?

Back 107

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 108

108. What are the clinical features of stromal tumors?

Back 108

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 109

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

Back 109

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 110

110. What are leiomyomas?

Back 110

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 111

111. What is the morphology of leiomyomas?

Back 111

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 112

112. What are the histologic characteristics of leiomyomas?

Back 112

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 113

113. What are the variant forms of leiomyomas?

Back 113

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 114

114. What are the clinical features of leiomyomas?

Back 114

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 115

115. What are leiomyosarcomas?

Back 115

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 116

116. What is the morphology of leiomyosarcomas?

How are they differentiated from benign leiomyomas?

Back 116

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 motses per 10 HPF with cellular atypia.

Front 117

117. What are the clinical features of leiomyosarcomas?

Back 117

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%.

Front 118

118. What is suppurative salpingits?

Back 118

Suppurative salpingitis may be caused by any of the pyogenic organisms, and often more than one is involved.

The gonococcus still accounts for more than 60% of cases of suppurative salpingitis, w/chlamydiae less often a factor. These tubal infections are part of PID.

Front 119

119. What is tuberculous salpingitis?

Back 119

Tuberculous salpingitis is extremely uncommon in the US and accounts for probably not more than 1-2% of all forms of salpingitis.

It is more common, however, in parts of the world where tuberculosis is prevalent and is an important cause of infertility in these areas.

Front 120

120. What is the most common primary lesion of the fallopian tube (excluding endometriosis)?

What are hydatids of Morgagni?

Back 120

The most common primary lesions are minute, 0.1 to 2-cm translucent cysts filled w/clear serous fluid, called paratubal cysts.

Larger varieties are found near the fimbriated end of the tube or in the broad ligaments and are referred to as hydatids of Morgagni. These cysts are presumed to arise in remnants of the mullerian duct and are of little significance.

Front 121

121. What are adenomatoid tumors (mesotheliomas)?

Back 121

These tumors of the fallopian tube are benign and occur subserosally on the tube or sometimes int eh mesosalpinx.

These small nodules are the exact counterparts of those described in relation to the testes or epididymis and are benign.

Front 122

122. What are primary adenocarcinomas of the fallopian tubes?

Back 122

Primary adenocarcinomas of the fallopian tubes are rare and are defined as an adenocarcinoma with a dominant tubal mass and luminal and mucosal involvement.

These tumors are detected by pelvic exam, abnormal discharge or bleeding, and occasionally, cervical cytology.

Approx 50% are stage I but nearly 40% of these patients will not survive 5 years.

Front 123

123. What genetic mutations are associated with primary adenocarcinomas of the fallopian tubes?

Back 123

Occult CA of the fallopian tube has been associated with BRCA mutations.

Front 124

124. What are the most common types of lesions encountered in the ovary?

Back 124

Functional or benign cysts and tumors.

Front 125

125. What are cystic follicles?

What is the morphology?

Back 125

Cystic follicles in the ovary are so common as to be virtually physiologic. They originate in unruptured graafian follicles or in follicles that have ruptured and immediately sealed.

These cysts are usually multiple. They range in size up to 2 cm in diameter, are filled w/a clear serous fluid, and are lined by a gray, glistening membrane.

Front 126

126. What are granulosa luteal cysts?

Back 126

Granulosa luteal cysts (corpora lutea) are normally present in the ovary. These cysts are lined by a rim of bright yellow luteal tissue containing luteinized granulosa cells. They occasionally rupture and cause a peritoneal reaction.

When advanced, the combination of old hemorrhage and fibrosis may make their distinction from endometriotic cysts difficult.

Front 127

127. What is polycystic ovarian disease?

Back 127

PCOD affects 3-6% of reproductive age women. The central abnormality is numerous cystic follicles or follicle cysts, often associated w/oligomenorrhea.

Patients w/PCOD have persistent anovulation, obesity, hirutism, and rarely, virilism.

Front 128

128. What is the pathogenesis of PCOD?

Back 128

Increased secretion of luteinizing hormone may stimulate the theca-lutein cells of the follicles, with excessive production of androgen, which is converted to estrone.

It is believed that a variety of enzyems involved in androgen biosynthesis are poorly regulated in PCOD.

There is a link of PCOD with type II DM and insulin resistance. Administration of insulin mediators has been associated with the resumption of ovulation.

Front 129

129. What is the morphology of PCOD?

Back 129

The ovaries are usually 2x normal size, gray-white with a smooth outer cortex, and are studded w/subcortical cysts 0.5-1.5 cm in diameter.

On histologic exam, there is a thickened superficial cortex beneath which are innumerable follicle cysts w/hyperplasia of the theca interna (follicular hyperthecosis). Corpora lutea are frequently but not invariably absent.

Front 130

130. What is stromal hyperthecosis?

Back 130

Stromal hyperthecosis, AKA cortical stromal hyperplasia, is a disorder of ovarian stroma most commonly seen in postmenopausal women, but it may blend with PCOD in younger women.

The disorder is characterized by uniform enlargement of the ovary (up to 7 cm) with a white to tan appearance. The involvement is usually bilateral and microscopically consists of hypercellular stroma with luteinization of the stroma cells, which are visible as discrete nests and vacuolated cytoplasm.

*Very similar to PCOD, but virilization may be striking

Front 131

131. What is theca lutein hyperplasia of pregnancy?

Back 131

This is a physiologic condition that mimics PCOD and stroma hyperthecosis during pregnancy.

In response to pregnancy hormones (GnTropins), proliferation of the theca cells w/expansion of the perifollicular zone occurs. As the follicles regress, the concentric theca-lutein hyperplasia may appear nodular.

Front 132

132. What are the risk factors for ovarian CA?

Back 132

Nulliparit, family history, and heritable mutations play a role in tumor development.

Gonadal dysgenesis in children is associated w/a higher risk.

Women 40-59 years of age who have taken oral contraceptives or undergone tubal ligation have an increased risk.

Front 133

133. What are the genetic factors in the pathogenesis of ovarian CA?

Back 133

1. Mutations in both BRCA1 and BRCA2 increase susceptibility to ovarian CA. BRCA1 mutations occur in about 5% of pts younger than 70. The risk of ovarian CA in women bearing BRCA1 or BRCA2 mutations is 20-60% by the age of 70 years. Most of these cancers are serous cystadenocarcinomas.

2. Approx 30% of ovarian adenocarcinomas express high levels of HER2/neu (ERB-B2) oncogene, which correlates w/a poor prognosis.

3. Mutations in p53 are found in 50% of ovarian CAs.

Front 134

134. Tumors of the ovary arise from one of which three ovarian components?

Back 134

1. Surface epithelium derived from either the coelomic epithelium or ectopic endometrial epithelium. The former gives rise to the mullerian epithelium during embryonic development. From it are derived the fallopian tubes, the endometrial lining, or the endocervical glands.

2. The germ cells, which migrate to the ovary from the yolk sac and are totipotential

2. The stroma of the ovary, which includes the sex cords, forerunners of the endocrine apparatus of the postnatal ovary.

Front 135

135. What are the characteristics of most ovarian tumors?

Back 135

Most are nonfunctional and tend to produce relatively mild symptoms until they have reached a large size.

Malignant tumors have usually spread outside the ovary by the time a definitive Dx is made.

Abdominal pain and distention, urinary and GI symptoms due to compression by tumor or CA invasion, and abdominal and vaginal bleeding are the most common symptoms.

The benign forms are entirely asymptomatic.

Front 136

136. Most primary neoplasms in the ovary fall within which category?

Back 136

Tumors of teh mullerian epithleium.

There are three major types of such tumors: serous, endometrioid, and mucinous tumors.

Componeents of the tumors may include cystic areas (cysadenomas), cystic and fibrous areas (cystadenofibromas), and predominantly fibrous areas (adneofibromas).

Front 137

137. The risk of tumor malignancy is a function of what?

Back 137

On gross exam, the risk of malignancy increases as a function of the amt of discernible solid epithelial growth, including papillary projections of soft tumor, thickened tumor lining the cyst spaces, or solid necrotic friable tissue depicting necrosis.

Front 138

138. What is the pathogenesis of mullerian epithelium tumors?

Back 138

The derivation of mullerian epithelial tumors is thru the transformation of coelomic mesothelium

This view is based on the embryologic pathway by which the mullerian ducts are formed and evolve into serous (tubal), endometrioid (endometrium), and mucinous (cervix) epithelia present in the normal female genital tract.

Front 139

139. Why do most mullerian epithelium tumors occur in the ovary?

Back 139

B/c coelomic epithelium is incorporated into the ovarian cortex to form mesothelial inclusion cysts.

Front 140

140. What are serous tumors?

Back 140

These common cystic neoplasms are lined by tall, columnar, ciliated epithelial cells are are filled w/clear serous fluid.

Together the benign, borderline, and malignant types account for about 30% of all ovarian tumors. About 75% are benign or of borderline malignancy and 25% are malignant.

Front 141

141. What is the prevalence of serous tumors?

Back 141

Serous cystadenocarcinomas account for approx 40% of all CAs of the ovary and are the msot common malignant ovarian tumors.

Benign and boderline tumros are most common btwn the ages of 20 and 50.

Cystadenocarcinomas occur later in life, although earlier in familial cases.

Front 142

142. What is the morphology of the characteristic serous tumor?

Back 142

The serous tumor may present on gross exam as either a cystic lesion in which the papillary epithelium is contained w/in a few fibrous walled cysts, or projecting from the ovarian surface.

Bilaterality is common. Concentric calcifications (psammona bodies) characterize serous tumors, although they are not specific for neoplasia when they are found alone.

Front 143

143. What is the morphology of benign serous tumors?

Back 143

In benign tumors, the lining epithelium is composed of a single layer of tall, columnar, ciliated epithelial cells with small, microscopic papillae.

The tumors typically present w/a smooth glistening cyst wall with no epithelial thickening or with small papillary projections (i.e., papillary cystadenoma).

Front 144

144. What is the morphology of borderline serous tumors?

Back 144

Borderline tumors contain an increased number of papillary projections.

They may contain increased complexity of the stromal papillae w/stratification of the epithelium and nuclear atypia, but destructive growth into the stroma is not seen.

Front 145

145. What is the morphology of frankly malignant serous tumors?

Back 145

Frankly malignant cystadenocarcinomas have multilayered epithelium w/many papillary areas and large, solid epithelial masses w/atypical cells focally invading the stroma.

In other words, larger amts of solid or papillary tumor mass, irregularity in the tumor mass, and fixation or nodularity of the capsule are all important indicators of probable malignancy.

Front 146

146. What are complex borderline tumors or low-grade micropapillary CAs?

Back 146

A small number of tumors have been described that share features of both borderline and malignant serous neoplasms, exhibiting epithelial complexity and a greater risk of invasive peritoneal implants.

Front 147

147. What determines the biologic behavior of serous tumors?

Back 147

Depends on degree of differntiation, distribution, and characteristics of the pitoneal implants, if present.

Unencapsulated serous tumors of the ovarian surface are more likely to extend to the peritoneal surfaces, and prognosis is closely related to the histologic appearance of the tumor and its growht pattern on the peritoneum.

Front 148

148. What is the prognosis for borderline and malignant tumors confined within the ovarian mass?

Involving the peritoneum?

Back 148

The 5-year survival rate for tumors confined w/in the ovarian mass is 100% and 70%, respectively.

The 5-year survival rate for the same tumors involving the peritoneum is about 90% and 25%, respectively.

Front 149

149. What are mucinous tumors of the ovary?

Back 149

These resemble their serous counterparts. They are somewhat less common, and occur principally in middle adult life and are rare before puberty and after menopause.

80% are benign or borderline, and about 15% are malignant.

Front 150

150. What is the morphology of mucinous tumors?

Back 150

In gross appearance, these tumors are characterized by more cysts of variable size and a rarity of surface involvement. They are less freq bilateral. These tumors tend to produce larger cystic masses, up to 25kg!

They appear grossly as multiloculated tumors filled with sticky, gelatinous fluid rich in glycoproteins.

Front 151

151. What are the histological characteristics of the four types of mucinous tumor?

Back 151

1. Histologically, the tumors lined by tall, columnar intestinal type epithelium are called intestinal-type mucinous cystomas.
2. Those w/papillary architecture and focal cilia are termed mullerian mucinous tumors, which may be associated with endometriosis.
3. Borderline tumors exhibit complex growth analogous to serous tumors, but lack solid growth or stromal infiltration.
4. Cystadenocarcinomas are usually of the intestinal type, and display solid tumor growth and invasion of stroma. (these are similar to colonic CA in appearance).

Front 152

152. What is pseudomyxoma peritonei?

Back 152

A condition associated w/mucinous ovarian neoplasms is pseudomyxoma peritonei. This disorder consists of an ovarian tumor w/extensive mucinous ascites, cystic epithelial implants on the peritoneal surfaces, and adhesions.

Pseudomyxoma peritonei, if extensive, may result in intestinal obstruction and death.

Front 153

153. What are endometrioid tumors?

Back 153

Most endometrioid tumros are carcinomas. They account for 20% of all ovarian CAs, and are distinguished from serious and mucinous tumors by the close resemblance of tubular glands to benign or malignant endometrium.

*Up to 50% of these tumors are associated w/endometriosis of the ovary.

Front 154

154. What is the morphology of endometrioid tumors?

Back 154

In gross appearance, endometrioid CAs present as a combo of solid and cystic areas, similar to other cystadenocarcinomas.

40% involve both ovaries, and such bilaterality usually, though not always, implies extension of the neoplasm beyond the genital tract. On histologic exam, glandular patterns bearing a strong resemblance to those of endometrial origin are seen.

The 5-year survival rate for pts w/stage I tumors is approx 75%.

Front 155

155. What is clear cell adenocarcinoma of the ovary?

Back 155

This uncommon pattern of surface epithelial tumor of the ovary is characterized by large epithelial cells w/abundant clear cytoplasm.

B/c these tumors sometimes occur in association w/endometriosis or endometrioid CA of the ovary and resemble clear cell CA of the endometrium, they are now thought to be of mullerian duct origin and variants of endometrioid adenocarcinoma.

The 5-year survival rate is approx 65% when confined to the ovaries, however, these tumors tend to be aggressive and thus the 5 year survival in the aggressive variants are dismal.

Front 156

156. What is the morphology of clear cell adenocarcinoma of the ovary?

Back 156

Again, these are characterized by large epithelial cells w/abundant clear cytoplasm.

They can be predominantly solid or cystic. In the solid neoplasm, the clear cells are arranged in sheets or tubules. In the cystic variety, the neoplastic cells line the spaces.

Front 157

157. What are cystadenofibromas?

Back 157

Cystadenofibromas are variants in which there is more pronounced proliferation of the fibrous stroma that underlies the columnar lining epithelium.

These benign tumors are usually small and multilocular and have simple papillary processes that do not become so complicated and branching as those found in the ordinary cystadenoma.

They may be composed of mucinous, serous, endometrioid, and transitional (Brenner tumors) epithelium.

Front 158

158. What are Brenner tumors?

Back 158

Brenner tumors are uncommon adenofibromas in which the epithelial component consists of nests of transitional cells resembling those lining the urinary bladder.

Less frequently, the nests contain microcysts or glandular spaces lined by column, mucin-secreting cells. For unknown reasons, Brenner tumors are occasionally encountered in mucinous cystadenomas.

Front 159

159. What is the morphology of Brenner tumors?

Back 159

These neoplasms may be solid or cystic, are usually unilateral (approx 90%), and vary in size from small lesions less than 1 cm in diameter to massive tumors up to 20 and 30 cm.

The fibrous stroma, resembling that of a normal ovary, is marked by sharply demarcated nests of epithelial cells resembling the epithelium of the urinary tract, often with mucinous glands in their center. Some neoplasms have hormonal activity, but these are rare.

Most Brenner tumors are benign, but borderline and malignant counterparts may be encountered.

Front 160

160. What is the clinical course of surface epithelial ovarian tumors?

Back 160

All large epithelial tumors cause similar symptoms, including lower abdominal pain, abdominal enlargement, and GI and urinary complains.

Resected benign tumors represent a cure. CAs in time extend thru the capsule, (or originate on the surface) and see the peritoneal cavity, occasionally causing massing ascites (characteristically, the ascites fluid is filled with diagnostic exfoliated tumor cells).

The malignant forms, however, tend to cause the progressive weakness, weight loss, and cachexia characteristic of all malignant neoplasms.

Front 161

161. How are ovarian CAs detected?

How can prevention be implemented?

Back 161

Specific biochemical markers for tumor antigens or tumor products in the plasma of these pts are being sought. One such marker is a HMW glycoprotein present in more than 80% of serous and endometrioid CAs, known as CA-125.

Both fallopian tubal ligation and oral contraceptive therapy are associated with significant reductions in relative risk.

Tubal ligation reduces risk by more than 1/2 and may be effective in subsets of women with BRCA mutations and family history of ovarian CA.

Front 162

162. What are mature (benign) teratomas?

Back 162

Most benign teratomas are cystic and are better known as dermoid cysts. These neoplasms are presumably derived from the ectodermal differentiation of totipotential cells. Cystic teratomas are usually found in young women during the active reproductive years.

Front 163

163. What is the morphology of mature (benign) teratomas?

Back 163

Benign teratomas are bilateral in 10-15% of cases.

They are unilocular cysts containing hair and cheesy sebaceous material. On section, they reveal a thin wall lined by an opaque, gray-white, wrinkled, apparent epidermis. From this epidermis, hair shafts frequently protrude. Within the wall, it is common to find tooth structures and areas of calcification.

*About 1% of the dermoids undergo malignant transformation of any one of the component elements (e.g. thyroid CA, melanoma, but mostly squamous cell CA).

Front 164

164. Where do teratomas come from?

Back 164

The current theory suggests origin from a meiotic germ cell. The karyotype of all benign ovarian teratomas is 46,XX. This suggests that tumors arise from an ovum after the first meiotic division.

Front 165

165. What are monodermal or specialized teratomas?

Back 165

Monodermal teratomas differentiate along the line of a single abnormal tissue. The most common is struma ovarii, composed entirely of mature thyroid tissue. These may cause hyperthyroidism.

Another example is the ovarian carcinoid, similar to carcinoids elsewhere in that it produces carcinoid syndrome via 5-hydroxytryptamine.

Front 166

166. What are immature malignant teratomas?

Back 166

These are rare tumors that differ from benign teratomas in that the component tissue resembles that observed in the fetus or embryo rather than in the adult.

The tumor is found chiefly in prepubertal adolescents and young women, the mean age being 18 years.

Front 167

167. What is the morphology of immature malignant teratomas?

Back 167

These tumors are bulky and have a smooth external surface. On section, they have a solid (or predominantly solid) structure. *There are areas of necrosis and hemorrhage.

Hair, grumous material, cartilage, bone, and calcification may be present.

On microscopic exam, there are varying amts of immature tissue differentiating toward cartilage, glands, bone, muscle, nerve and others.

*Extraovarian spread is linked to tumor grades I-III, which is based on the proportion of tissue containing immature neuroepithelium.

Front 168

168. What are the clinical features of immature malignant teratomas?

Back 168

These teratomas grow rapidly and freq penetrate the capsule w/local spread or metastases. Stage I tumors, however, particularly those w/low grow (grade 1) histology, have an excellent prognosis.

Front 169

169. What is a dysgerminoma?

Back 169

Dysgerminoma is the ovarian counterpart of the seminoma of the testes.

It is composed of large vesicular cells having a clear cytoplasm, well defined cell boundaries, and centrally placed regular nuclei.

They may occur in childhood, but 75% occur in the second and third decades. Some occur in pts with gonadal dysgenesis, including pseudohermaphroditism.

Front 170

170. What is the morphology of a dysgerminoma?

Back 170

Most are nonfunctional. Of lesions, 80-90% are usually unilateral. The tumors are solid, yellowish white to gray-pink, and fleshy.

Histologically, they consist of sheets and cords of large vesicular cells separated by scant fibrous stroma.

Front 171

171. What are the clinical features of dysgerminomas?

Back 171

All are malignant, but the degree of histologic atypia is variable, and only about 1/3 are aggressive.

Thus, a unilateral tumor that has not broken thru the capsule and has not spread has an excellent prognosis after simple salpingo-oophorectomy.

Overall survival exceeds 80%.

Front 172

172. What are endodermal sinus (yolk sac) tumors?

Back 172

This tumor is rare but is the second most common malignant tumor of germ cell origin. It is thought to be derived from differentiation of malignant germ cells toward extraembryonic yolk sac structure. Similar to the yolk sac, this tumor is rich in AFP and alpha1 antitrypsin.

Front 173

173. What are the characteristic features of yolk sac tumors?

Back 173

Its characteristic histologic feature is a glomerulus-like structure composed of a central blood vessel enveloped by germ cells w/in a space lined by germ cells (Schiller-Duval body).

Hyaline droplets are present in all tumors, and some of these can be stained for AFP by immunoperoxidase techniques.

Front 174

174. What is a choriocarcinoma?

Back 174

Choriocarcinoma arises in the ovary from the teratogenous development of germ cells. Most such tumors exist in combination with other germ cell tumors.

Histologically, they are identical to the more common placental lesions and, analogous to gestational choriocarcinoma, elaborate chorionic gonadotropins (HCG).

These tumors are highly malignant, metastasize widely, and are much more resistant to chemo than their placental counterparts.

Front 175

175. What are three other germ cell tumors worthy or my knowing?

Back 175

1. Embryonal carcinoma, another highly malignant tumor of primitive embryonal elements
2. Polyembryoma, a malignant tumor containing so-called embryoid bodies
3. Mixed germ cell tumors containing various combos of dysgerminoma, teratoma, endodermal sinus tumor, and choriocarcinoma

Front 176

176. What are granulosa-theca cell tumors?

Back 176

These tumors are composed of varying proportions of granulosa and theca cell differentiation. These tumors are composed almost entirely of granulosa cells or a mixture of granulosa and theca cells.

Approx 2/3rds occur in postmenopausal women.

Front 177

177. What is the morphology of granulosa-theca cell tumors?

Back 177

Granulosa tumors are usually unilateral and vary from microscopic foci to large, solid, and cystic encapsulated masses. Tumors that are hormonally active have a yellow coloration to their cut surfaces, produced by contained lipids. The pure thecomas are solid, firm tumors.

Front 178

178. What are the histologic patterns of granulosa-theca cell tumors?

Back 178

The small, cuboidal to polygonal cells may grow in anastomosing cords, sheets, or strands. In occasional cases, small, distinctive, gland-like structures filled w/an acidophilic material recall immature follicles (Call-Exner bodies).

The thecoma component consists of clusters or sheets of cuboidal to polygonal cells. In some tumors, the granulosa or theca cells may appear more plump w/ample cytoplasm chracteristic of luteinization.

Front 179

179. What are two reasons for why granulosa-theca cell tumors have clinical importance?

Back 179

1. Their potential elaboration of large amts of estrogen, and thus to produce precocious sexual development and endometrial hyperplasia; they predispose to endometrial CA.
2. The small but distinct hazard of malignancy in the granulosa cell forms. All granulosa cell tumors are potentially malignant. Pure thecomas are benign.

Front 180

180. What is the relationship of inhibin and granulosa-theca cell tumors?

Back 180

Recently, elevated tissue and serum levels of inhibin, an ovarian product, have been associated w/granulosa cell tumors.

Front 181

181. What are fibroma-thecomas?

Back 181

Fibroma-thecomas are common forms of ovarian neoplasms. They are usually unilateral, solid, an hard, gray-white masses made up histologically of well-differentiated fibroblasts.

Of fibromas, 40% are associated with hydrothorax (usually right-sided) and ascites (Meigs syndrome).

Front 182

182. What are setoli-leydig cell tumors (androblastomas)?

Back 182

These tumors commonly produce masculinization or at least defeminization, but a few have estrogenic effects. They occur in women of all ages, although the peak incidence is in the second and third decades.

These tumors are unilateral and resemble granulosa-theca cell neoplasms.

Front 183

183. What is the morphology of androblastomas?

Back 183

The cut surface is usually solid and varies from gray to golden brown in appearance. On histologic exam, the well-differentiated tumors exhibit tubules composed of Sertoli cells or Leydig cells interspersed with stroma. The intermediate forms show only outlines of immature tubules and large eosinophilic Leydig cells.

The poorly differentiated tumors have a sarcomatous pattern with a disorderly disposition of epithelial cell cords.

Heterologous elements, such as mucinous glands, bone, and cartilage, may be present in some tumors.

Front 184

184. What are hilus cell tumors (pure Leydig cell tumors)

Back 184

These tumors are derived from the hilar cells of the ovary and are rare, unilateral, and characterized histolgoically by large lipid laden cells w/distinct borders. Reinke crystalloids are usually present.

Typically, pts w/hilus cell tumors present w/evidence of masculiziation, hirsutism, voice changes, and clitoral enlargement.

Front 185

185. What is the most consistent laboratory finding in hilus cell tumors?

Back 185

An elevated 17-ketosteroid excretion level unresponsive to cortisone suppression

Front 186

186. What is a pregnancy luteoma?

Back 186

The ovary in pregnancy may exhibit microscopic nodular proliferation of theca cells in response to gonadotropins.

Rarely, a frank tumor may develop (termed pregnancy luteoma) that closely resembles a corpus luteum of pregnancy. These tumors have been associated with virilization in pregnant pts and in their respective female infants.

Front 187

187. What is a gonadoblastoma?

Back 187

A gonadoblastoma is an uncommon tumor thought to be composed of germ cells and sex cord stroma derivatives. It occurs in individuals w/abnormal sexual development and in gonads of indeterminate nature.

80% of pts are phenotypic females, and 20% are phenotypic males with undescended testicles and female internal secondary organs.

Front 188

188. What about small cell carcinoma of the ovary?

Back 188

These malignant tumors occur predominantly in young women and may be associated w/hypercalcemia.

Front 189

189. What is a Krukenberg tumor?

Back 189

A classic example of metastatic GI neoplasia to the ovaries is termed Krukenberg tumor, characterized by bilateral metastases composed of mucin-producing, signet-ring cancer cells, most often of gastric origin.

Front 190

190. What is an ectopic pregnancy?

Back 190

Ectopic pregnancy denotes implantation of the embryo in a site other than the uterus- most commonly the fallopian tubes (90%) but also rarely in the ovary or abdominal cavity.

Predisposing factors include PID w/chronic salpingitis and peritubular adhesions, but 50% occur in apparently normal tubes.

Front 191

191. What is the morphology of tubal pregnancies?

Back 191

In tubal pregnancy, the placenta is poorly attached to the wall of the tube. Intratubal hemorrhage may thus occur from partial placental separation w/o tubal rupture.

Tubal pregnancy is the most common cause of hematosalpinx and should always be suspected when a tubal hematoma is present. More often, the placental tissue invades the tubal wall and causes tubal rupture and intraperitoneal hemorrhage.

Front 192

192. What is the clinical course of ectopic pregnancies?

Back 192

The clinical course is punctuated by the onset of severe abdominal pain about 6 weeks after a previous normal menstrual period, when rupture of the tube leads to pelvic hemorrhage.

In such cases, the pt may rapidly develop a shocklike state w/signs of an acute abdomen.

Front 193

193. What is an abruptio placentae?

Back 193

Retroplacental hemorrhage at the interface of placenta and myometrium (abruptio placentae) will threaten both mother and fetus.

Front 194

194. What is placenta accreta?

Give me 2 reasons why it is important...

Back 194

Placenta accreta is caused by partial or complete absence of the decidua w/adherence of the placenta directly to the myometrium.

It is important b/c:
1. postpartum bleeding, often life-threatening, occurs b/c of failure of placental separation
2. in up to 60% of cases, it is associated with placenta previa, often with serious antepartum bleeding and premature labor

Front 195

195. What is placenta previa?

Back 195

Placenta previa is a condition in which the placenta implants in the lower uterine segment or cervix.

Front 196

196. What are twin placentas?

Back 196

There are three basic types:
1. Dichorionic diamnionic (which may be fused)
2. Monochorionic diamnionic
3. Monochorionic monoamnionic.

Monochorionic placentas imply identical twins. Dichorionic occurs with either monozygotic or dizygotic twins.

Front 197

197. What are the two ways in which infections may reach the placenta?

Back 197

1. Ascending infection thru the birth canal
2. Hematogenous (transplacental) infection.

Ascending infections are by far the most common and are most often bacterial; in many such instances, localized infection of the membranes by an organism produces premature rupture of membranes and entry of the organisms.

Front 198

198. What is toxemia of pregnancy (preeclampsia and eclampsia)?

Back 198

Toxemia of pregnancy refers to a symptom complex characterized by hypertension, proteinuria, and edema (preeclampsia). Patients w/eclampsia develop DIC with lesions in the liver, kidneys, heart, placenta, and sometimes the brain.

Eclampsia is the severe form associated with convulsions and coma. Toxemia occurs in 6% of pregnancies, usually in the last trimester, and is most common in primiparas.

Front 199

199. What is the pathogenesis of toxemia of pregnancy?

Back 199

Three events seem to be of prime importance in this disorder:
1. Placental ischemia
2. Hypertension
3. DIC

Front 200

200. Why is placental ischemia important?

Back 200

The causes of the initial events are unknown but evidence points to abnormality of placentation, leading to placental ischemia.

The net effect is a shallow implantation with incomplete conversion of decidual vessels to vessels adequate for the pregnancy state. An intrinsic defect in the invading trophoblast may contribute to altered vascular flow. These defects in trophoblastic conversion may further influence remodeling of uterine vasculature, reducing blood flow, and leading to placental ischemia.

Front 201

201. What is the result of decreased uteroplacental perfusion?

Back 201

Decreased uteroplacental perfusion leads to stimulation of vasconstrictor substances (thromboxane, angiotensin, endothelin) and the inition of vasodilator influences (PGI2, PGE, NO) from the ischemic placenta.

DIC, hypertension, and organ damage then develop.

Front 202

202. What causes the DIC in toxemia?

Back 202

Endothelial damage, abnormalities in the level and activities of coagulation factors, and primary platelet alteration may play a role.

For example, during toxemia, the placental ischemia leads to a higher output of thromboplastic substances, and antithrombin III levels are reduced.

Front 203

203. What causes the toxemic hypertension?

Back 203

One mechanism involves renin-angiotensin and prostaglandins. Normal pregnant women develop a resistance to the vasoconstrictive and hypertensive effects of angiotensin, but women w/toxemia lose such resistance, developing a tendency to hypertension.

This is probably the results of decreased prostaglandin E in women w/toxemia. Also, renin levels are increased.

*Administration of sFlt1 to pregnant rats produces the characteristic systemic and renal abnormalities seen in human preeclampsia.

Front 204

204. What is the morphology of toxemia?

Back 204

The placenta is the site of changes; most of which reflect ischemia and vessel injury. This takes of the form of placental infarcts, retroplacental hematomas, increased villous ischemia, ***fibrinoid necrosis and intramural lipid deposition (acute atherosis).

Front 205

205. What are the clinical features of preeclampsia and eclampsia?

Back 205

Preeclampsia usually occurs after the 32nd week of pregnancy and is characterized by hypertension, edema, proteinuria, headaches, and visual disturbances. Mild toxemia can be controlled by bed rest, diet, and antihypertensive meds, but delivery is the only definitive treatment for established toxemia.

Front 206

206. What is intrauterine growth restriction?

Back 206

Intrauterine growth restriction is an important cause of infant mortality and morbidity and is defined as a birth weight below the 10th percentile.

Major causes include obvious fetal disorders such as chromosomal abnormalities and malformations, and maternal vascular disease, including toxemia.

Front 207

207. What is a hydatidaform mole?

Back 207

Hydatidaform mole is characterized by cystic swelling of the chorionic villi, accompanied by variable trophoblastic proliferation.

These may precede choriocarcinoma. Most pts present in the fourth or fifth month with vaginal bleeding and with a uterus that is usually, but not always, larger than expected for the duration of pregnancy.

Front 208

208. What is the pathogenesis of hydatidaform moles?

Back 208

There are type types of benign noninvasive moles, complete, and partial, that can be differentiated by histologic, cytogenetic, and flow cytometric studies.

In a complete mole (46,XX), one or two sperm fertilize an egg that has lost its chromosomes; all genetic material is therefore paternally derived.

In a partial mole, an egg with normal chromosomal content is fertilized by one diploid or two haploid sperm to get a triploid (69,XXY) complement of genetic material.

Front 209

209. What is the morphology of partial and complete moles?

Back 209

Grossly, moles consist of masses of thin walled, translucent, cystic, grapelike structures. Fetal parts are rarely seen in complete moles and are more common in partial moles.

Microscopically, complete moles show hydropic swelling of villi, inadequate vascularization of villi, and significant trophobalstic proliferation. Partial moles show only focal edema and slight trophoblastic proliferation.

Front 210

210. How are hydatidaform moles detected?

Back 210

Partial and complete moles can be distinguished by the expression of the normally maternally imprinted p57 gene that is not expressed in the cytotrophoblast and stromal cells of the paternally derived mole. B/c p57 is maternally imprinted, and both the X chromosomes in complete moles are derived from the father, there is no expression of p57 protein in complete modles.

Most moles can be Dx via ultrasound exam and by quantitative analysis of serum hCG, revealing levels exceeding those produced by a normal pregnancy of similar age.

Front 211

211. What is an invasive mole?

Back 211

An invasive mole penetrates and may even perforate the uterine wall, marked by active proliferation of both cytotrophoblasts and syncytiotrophoblasts.

It does not metastasize. It is associated w/a persistent elevated hCG level and varying degrees of luteinization of the ovaries. The tumor responds well to chemo.

Front 212

212. What is choriocarcinoma?

Back 212

Choriocarcinoma is an epithelial malignant neoplasm of trophoblastic cells derived from any form of previous normal or abnormal pregnancy.

About 50% arise in hydatidaform mole, 25% in previous abortions, 22% in normal pregnancies, and the rest in ectopic pregnancy.

Front 213

213. What is the morphology of choriocarcinomas?

Back 213

The choriocarcinoma is classically large, soft, yellowish white, and has a marked tendency to form large pale areas of ischemic necrosis, foci of cystic softening, and extensive hemorrhage.

Front 214

214. What is the clinical course of choriocarcinomas?

Back 214

Choriocarcinomas are manifested by vaginal bleeding and discharge that may appear in the course of an apparently normal pregnancy, after a miscarriage, or after curettage.

hCG titers are elevated to levels above those seen in hydatidaform moles.

When the condition is first discovered, widespread metastases may have already occurred. However, choriocarcinomas are highly sensitive to chemo and cure can be achieved even in pts w/metastatic disease.

Front 215

215. What are placental site trophoblastic tumors?

Back 215

Placental site trophoblastic tumors are a rare tumor composed of proliferating intermediate trophoblasts that are larger than cytotrophoblasts but mononuclear rather than syncytial.

The lesion differs from that of choriocarcinoma in the absence of cytotrophoblastic elements and low levels of hCG production.

Most are locally invasive and malignant variants are distinguished by a high mitotic index, extensive necrosis, and local spread. About 10% result in metastases and death.