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Flashcards in Pathology-Female Repro Lecture Deck (66):
1

Low risk HPV

6 & 11. These cause condylomas and warts

2

High risk HPV

16 (60% of carcinomas) & 18 (10% of carcinomas). 100% of HSIL are associated with these and 80% of LSIL are associated with these.

3

Risk factors for cervical cancer (5)

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Multiple sex partners, immunosuppression, HLA, OCP and smoking

4

What is the natural course of 90% of HPV infections?

90% are eliminated by the immune response within 2 years. The 10% whose infection does not resolve it takes ~10 years to become malignant.

5

Why does HPV has such a predilection for causing cervical cancer at the zone of transition?

It infects immature mataplastic epithelium at the squamocolumnar junction.

6

How does HPV induce koilocytic atypia in maturing squamous cells?

Interference with tumor suppressor genes Rb and p53.

7

How do you stage cervical cancer?

Low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL)

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8

What is the progression of HPV infection to cervical cancer?

Note that 60% of LSIL regress in 2 years, 30% persist and 10% progress to HSIL. Note that 30% of HSIL regress, 60% persist and 10% progress to carcinoma.

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9

What would you expect to see on pap smear of the transformation zone biopsy shown below?

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The biopsy shows a normal squamo-columnar junction so you would expect to see normal squamous and glandular cells.

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10

What would you expect to see on pap smear of the transformation zone biopsy shown below?

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The biopsy shows HSIL and you would expect to see abnormal squamous cells with hyperchromatic nuclei and glandular cells with a high N:C ratio.

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11

What would you expect to see on biopsy of low grade SIL?

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Koilocytosis and nuclear atypia.

12

What is the most common vulvar malignancy?

Vulvar squamous cell carcinoma. Note the nests of squamous cells invading the surrounding stroma.

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13

Demographic population that typically gets vulvar squamous cell carcinoma?

2/3 in women > 60 years old. 70% associated with lichen sclerosis and squamous hyperplasia. 30% are HPV-associated.

14

What is the pathophysiology behind lichen sclerosis?

As you approach menopause estrogen levels drop and vulvar squamous epithelium begins to thin due to degeneration of collagen and dense inflammatory infiltrate follows and changes start with vulvar intraepithelial neoplasia (VIN) and islands of keratinizing well-differentiated squamous cell carcinoma.

15

How does the prognosis of vulvar squamous cell carcinoma differ between etiologies of lichen sclerosis/squamous hyperplasia and HPV?

Lichen sclerosis/squamous hyperplasia has a worse prognosis.

16

What are patients likely to have if they present with crusting and eczema on the nipple and a biopsy that shows Paget disease of the nipple? What if they only had extramammary Paget disease on the vulva?

Nippe = underlying breast carcinoma. Vulvar = no underlying cancer.

17

A 60 year old woman presents with pruritic, red, crusty areas on the labia majora. Biopsy show large anaplastic cells with halos in the epidermis. What is your diagnosis?

Vulvar Paget disease.

18

What will you often find at the same time you find vaginal squamous cell carcinoma?

Vaginal Intraepithelial Neoplasia (VAIN). HPV dysplasia progresses to VAIN then to SCC.

19

What disease is associated with DES exposure?

Vaginal adenosis and clear cell adenocarcinomas. Exposure to DES during pregnancy yields girl babies with glandular columnar epithelium below the squamous epithelium in the upper 1/3 of the vaginal wall.

20

A 5 year old girl presents with translucent grape-like clusters protruding from the vagina. You treat her with surgery and chemotherapy. What is her diagnosis?

Embryonal rhabdomyosarcoma (i.e. sarcoma botryoides)

21

A patient presents with menorrhagia, dysmenorrhea, dyspareunia, pelvic pain and an enlarged uterus. Uterine biopsy is shown below. What is your diagnosis?

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Adenomyosis. This is infiltration of benign endometrial glands and stroma deep into the myometrium.

22

A 24 year old woman presents with infertility, dysmenorrhea, pelvic pain and dyspareunia. Laparoscopic evaluation shows endometrial glands and stroma in the ovaries and uterine ligaments. What are 3 possible etiologies of this condition?

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Endometrial glands and stroma outside the endometrial cavity = endometriosis. The three theories are 1) Regurgitation of retrograde menstruation through fallopian tubes into the peritoneal cavity 2) Metaplasia from coelomic epithelium 3) Vascular/lymphatic dissemination (explains endometriosis in the lung).

23

Why does endometriosis cause pain?

Inflammatory reaction. The glands and stroma actually cycle like the normal endometrium. When they do this it causes an intense inflammatory reaction and pain.

24

A 45 year old woman presents with abnormal uterine bleeding. Her biopsy is shown below. What is causing her condition? How can it be treated?

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Note the large endometrial glands with little stroma. This is typical of endometrial hyperplasia. This typically occurs due to high levels of estrogen, decreased progestins and hyperplasia of the endometrial glands. This can be treated with supplementary progestins or D&C.

25

A patient is diagnosed with atypical endometrial hyperplasia. How is she likely treated?

This type of endometrial hyperplasia has atypical nuclei and has a higher risk for causing endometrial cancer. These patients have a hysterectomy because they likely have underlying endometrial cancer.

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26

Endometrial hyperplasia with cystic architectural alterations in glands but no cytologic atypia. What is the risk of progressing to CA? What if there was cytologic atypia?

Simple hyperplasia. W/o atypia there is a 1% risk of CA. W/atypia risk is 8%.

27

Endometrial hyperplasia with increased number and size of glands that are crowding and budding but no cytologic atypia. What is the risk of progressing to CA? What if there was cytologic atypia?

Complex hyperplasia w/o atypia has a 3% risk of CA. Complex hyperplasia w/atypia (cytomegaly, loss of polarity, vesicular nuclei, nucleoli, increased N:C ratio) has a risk of 23-48% of progressing to CA>

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28

Two types of endometrial adenocarcinoma

Type I (80% of cases, arises secondary to endometrial hyperplasia in younger patients). Type II (15% of cases, associated with endometrial atrophy/EIN in older patients).

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29

What mutations are seen in 30-80% of endometrial adenocarcinomas and 20% of endometrial hyperplasias?

PTEN

30

Most common type of endometrial carcinoma?

Type I endometriod: similar to endometrial hyperplasia and associated with estrogen exposure. Note that stage I 5-year survival is 90%

31

What types of endometrial carcinoma are high grade regardless of histological differentiation?

Papillary serous carcinoma and clear cell carcinoma. Note that stage II serous type has a 35% 5-year survival rate.

32

What is your diagnosis in this patient who had an endometrial biopsy?

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Note the “back-to-back” endometrial glands that are well-differentiated, this is a rare form. Most are moderately or poorly differentiated with malignant glands or solid sheets of malignant cells.

33

Large leaf-like (polypoid) endometrial growths in a 40-50 year old woman with low grade malignancies

Adenosarcomas of the endometrial stroma.

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34

How are endometrial stromal tumors divided

There are adenosarcomas and stromal tumors. Stromal Tumors: Benign stromal nodules (low and high grade) and endometrial stromal sarcomas (low and high grade).

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35

What is the most common tumor in women?

Leiomyoma (fibroids).

36

A woman presents with abnormal bleeding, urinary frequency, abdominal pain, bloating, pressure and miscarriage. Uterine biopsy shows whorled bundles of smooth muscle that has grown since her pregnancy. What is her risk for malignancy?

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Low. Leiomyomas rarely progress to leiomyosarcomas. Leiomyosarcomas will have nuclear atypia, mitosis and necrosis (shown below).

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37

A woman presents with oligomenorrhea, hirsutism and obesity. Labs show elevated androgens, estrone and LH. What would you expect to see on examination of her ovaries?

Bilaterally enlarged ovaries with multiple cystic follicles that do not ovulate. This is polycystic ovary disease (Stein-Leventhal syndrome). Note that this may lead to endometrial hyperplasia and adenocarcinoma.

38

What population are most benign ovarian tumors found? Malignant?

Benign in young women. Malignant in women 45-65.

39

Risk factors for ovarian cancer

Nulliparity, family history (BRCA1/BRCA2). Decreased risk with OCPs and tubal ligation.

40

Aside from BRCA1/BRCA2, what mutations are associated with ovarian cancer?

HER2 (poorer prognosis), p53 (50% of cancers) and k-RAS (in mucinous tumors)

41

A patient presents with bloating, abdominal pain, urinary urgency and fatigue. Family history reveals BRCA1 mutations. Transvaginal U/S shows an ovarian mass that is later removed. What tumor marker could you use to track for recurrence?

CA-125

42

4 tumors that can arise in the ovaries

Surface epithelial-stroma (65% of all ovarian tumors, 90% of all ovarian malignancies), Germ cell tumors (20% of all ovarian tumors, 3% of all malignancies), Sex cord-stromal tumors (10% of all ovarian tumors, 2% of all malignancies). Metastatic ovarian tumors (5% of all tumors, 5% of all malignancies)

43

5 types of surface epithelial ovarian tumors

Serous, mucinous, endometrioid, clear cell and transitional (Brenner). Serous (45% of malignant ovarian tumors) and mucinous are most common.

44

Benign surface epithelial ovarian tumor

Cystadenoma.

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45

What is your diagnosis of this ovarian mass?

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Note the cysts are lined with large papillae. If you looked closer the pap illations are lines with atypical cells. Sometimes you may see psammoma bodies. This is a Borderline (low malignant potential) serous tumor.

46

What is your diagnosis of this ovarian mass?

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Serous Cystadenocarcinoma (Papillary Serous Carcinoma). Note the large polypoid projections, stratified lining w/cellular atypia, stromal invasion, psammoma bodies.

47

When do you most often see mucinous tumors?

When there is another malignancy in the GI tract. Note that this is more often unilateral where serous cystadenocarcinomas are more often bilateral.

48

What is your diagnosis of this ovarian mass?

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Mucinous tumor. Note the multilocular, thin-walled cysts with thick mucinous conent. Also note the single row of mucin-filled columnar epithelium w/o atypia. A borderline (LMP) mucinous cystadenoma would have atypia.

49

You biopsied a mass in the ovary and got this result. What should you do next?

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Note the malignant back-to-back tubular glands indicating an endometrioid ovarian tumor. These often arise in conduction with endometrial tumors, so you should check the uterus next.

50

5 main types of germ cell tumors

Teratoma, dysgerminoma, choriocarcinoma, yolk sac tumor and embryonal carcinoma

51

What is the most common type of teratoma you will find in the ovary?

Cystic mature teratomas (i.e. dermoid cysts). These are benign and have all three germ lines represented. The remainder of the cells are immature (malignant) and monodermal.

52

What is your diagnosis of this ovary? What is the prognosis?

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Note the stratified squamous lining with cartilage, thyroid, GI mucosa, hair, sebum, teeth etc. These are mostly benign, but turn to SCC, thyroid carcinoma (strum ovarii w/ hyperthyroidism) and melanoma when malignant.

53

Teratomas seen in prepubertal adolescents w/ immature neuroepithelial elements and good prognosis?

Immature teratomas.

54

Most common sex cord-stromal tumors

Granulosa-theca cell (w/precocious puberty or endometrial hyperplasia/CA) tumors and leydig cell (masculinizing) tumors.

55

When to stain an ovarian tumor for inhibin?

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Granulosa cell tumors, note the coffee-bean appearance w/Call-Exner bodies.

56

Hormonally inactive ovarian tumors that may present with Meigs syndrome and basal cell nevus syndrome?

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Fibroma-Thecomas. Meigs syndrome = tumor + hydrothorax.

57

Common metastatic ovarian tumor that is bilateral w/signet ring cells

Kruckenberg (from stomach)

58

Metastatic ovarian tumor from appendix

Pseudomyxoma peritonei

59

A woman presents with hypertension, edema, proteinuria and convulsions during pregnancy. What is the most likely condition?

Eclampsia.

60

A pregnant woman comes in at 16 weeks with an oversized uterus. She has hypertension and you note vaginal bleeding and ovarian enlargement on pelvic exam. Labs show hCG > 100,000. What would you expect to see on ultrasound and biopsy?

She likely has a complete mole and U/S will show a snowstorm pattern. Biopsy would show malignant proliferation of chorionic villi and syncytiotrophoblasts.

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69 XXX, fetal parts present, not all villi are hydropic and sparse trophoblastic proliferation.

Partial mole.

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62

46 XX, fetal parts absent, all villi edematous, circumferential trophoblast proliferation

Complete mole

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63

An expecting woman presents at 19 weeks gestation. Her uterus is small for her gestational age. She states that she has moderate uterine bleeding and hypertension. Labs show a normal hCG. Biopsy is shown below. What is the likely diagnosis? 

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Partial mole. Note that not all villi are hydropic and trophoblastic proliferation is sparse.

64

A woman presents with persistently elevated hCG levels after a mole pregnancy is evacuated. Biopsy shows molar villi with trophoblast proliferation in the myometrium. How do you treat her?

She has an invasive mole which can lead to uterine perforation and life-threatening bleeding. It can also progress to choriocarcinoma. This is treated by hysterectomy.

65

A 30 year old woman presents with abnormal uterine bleeding a few months after evacuation of a molar pregnancy. hCG levels are markedly elevated and biopsy is shown below. What is your diagnosis?

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Choriocarcinoma, note the proliferation of syncytiotrophoblasts and cytotrophoblasts without formation of villi.

66

A patient presents with a term pregnancy. Labs show low hCG levels.After delivery a mass is found in her uterus and biopsy is shown below. What is your diagnosis? What is a major complication?

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Placental Site Trophoblastic Tumor. Note the soft, hemorrhagic and necrotic appearance. Note the myometrial invasion. Note that 10-15% of women can die from disseminated disease.