1. Female Reproductive System
Kristine Krafts, M.D.

2. Female Reproductive System Outline
Cervix
Uterus
Ovaries
Breast

3. Female Reproductive System Outline
Cervix
Cervical carcinoma

4. Cervical Carcinoma
Once the most common cancer in women – now not even in top 10.
Decrease due to Pap test!
At the same time, precursor lesions are increasing (early detection)

5. Cervical Intraepithelial Neoplasia (CIN)
Precursor to carcinoma
Almost all carcinomas arise in CIN; but not all cases of CIN progress to carcinoma!
Three grades:
CIN I: mild dysplasia (half regress, 20% progress)
CIN II: moderate dysplasia
CIN III: severe dysplasia (30% regress, 70% progress)
The higher the grade, the more likely the lesion will progress to carcinoma

6. Cervical Carcinoma Risk Factors
Early age at first intercourse
Multiple sexual partners
A male partner with multiple previous partners
Persistent infection with “high-risk” HPV
Smoking
Immunodeficiency

7. Cervical Carcinoma and HPV
HPV is detectable in almost all CIN and cancer.
“High-risk” types:
16, 18, 45, 31
Found in carcinomas
Integrate into genome, inactivate p53, RB
“Low-risk” types:
6, 11
Found in condylomas (benign lesions)
Do not integrate into genome

9. Development of transformation zone

10. Normal cervix, young adult
Transformation zone
Normal cervix, young adult

11. Transformation zone

12. Spectrum of cervical intraepithelial neoplasia (CIN)

13. Normal turning into CIN

15. Cytology of CIN (Pap smear)
normal
CIN I
CIN II
CIN III
Cytology of CIN (Pap smear)

16. Cytology of CIN (Pap smear)
normal
CIN I
CIN II
CIN III
“High-grade
dysplasia”
“Low-grade dysplasia”
Cytology of CIN (Pap smear)

17. Invasive Cervical Carcinoma
Most cases are squamous, arising from CIN
Small number are adenocarcinomas
Peak age: 45 (10-15 years after CIN develops!)
Spreads slowly
Most cases are diagnosed early
Mortality is related to stage
Stage 0 (preinvasive): 100% 5 year survival
Stage 4: 10% 5 year survival

18. Cervical carcinoma

19. Cervical carcinoma

20. Female Reproductive System Outline
Cervix
Uterus
Endometriosis
Endometrial hyperplasia
Tumors

21. Endometriosis Location of endometrial glands outside uterus
Usually peritoneum, rarely lymph nodes
Endometrium undergoes cyclic bleeding
Causes scarring, pain, sometimes sterility
How does endometrium get out?

23. Endometriosis in ovary (“chocolate cyst”)

24. Endometrial Hyperplasia
Proliferation of endometrium due to estrogen excess
Risk factors: anovulatory cycles, obesity, estrogen-producing ovarian tumors, exogenous hormone use
Three categories: simple, complex, and atypical
The more severe the hyperplasia, the greater the chance that it will evolve into carcinoma

25. Normal endometrium

26. Endometrial hyperplasia
Simple
Complex
Atypical
Endometrial hyperplasia

27. Leiomyoma “Fibroid” Benign tumor of smooth muscle Common!
Stimulated by estrogen
Menorrhagia, metrorrhagia, or asymptomatic

28. Leiomyosarcoma Malignant tumor of smooth muscle
Necrotic, with atypical cells and lots of mitoses
Often recur after surgery
Many metastasize, especially to lungs
5 year survival = 40%

29. Leiomyoma
Leiomyosarcoma

30. Leiomyoma
Leiomyosarcoma

31. Endometrial Carcinoma
Peak age: (not before 40)
Frequently arises in endometrial hyperplasia
Risk factors: obesity, nulliparity, estrogen replacement
Symptoms: leukorrhea, irregular bleeding
Metastasizes late

32. Endometrial adenocarcinoma

33. Female Reproductive System Outline
Cervix
Uterus
Ovaries
Tumors

34. Origin of Ovarian Tumors
Surface epithelial tumors
Germ cell tumors
Sex cord-stromal tumors
Cystadenoma
Cystadenocarcinoma
Teratoma
Dysgerminoma
Yolk sac tumor
Choriocarcinoma
Granulosa-theca cell tumor
Sertoli-Leydig cell tumor

35. Cystadenoma Benign tumor derived from surface epithelium
Repeated ovulation, scarring, infolding of epithelium leads to cysts, which can undergo neoplastic transformation
Typically large, occasionally bilateral

36. Patient with ovarian cystadenoma

37. Patient with ovarian cystadenoma

38. Ovarian cystadenoma

39. Ovarian cystadenoma

40. Ovarian cystadenoma

41. Teratoma
Benign tumor with differentiation along all three germ cell layers (ectoderm, endoderm, mesoderm)
Usually cystic, with skin inside (“dermoid cyst”)
Sebaceous material, matted hair, teeth, bone…
Malignant variant has immature tissues

42. Teratoma

43. Teratoma

44. Ovarian Cancer 22,000 new cases / 14,000 deaths predicted in 2014
5th commonest, 5th most deadly cancer in women
Danger: no definitive signs until advanced
Peak age: 50
Most are cystadenocarcinomas

45. Papillary cystadenocarcinoma

46. Papillary cystadenocarcinoma

47. Ovarian Cancer Symptoms Feeling of fullness or bloating Pelvic pain
Back pain
Abnormal menses
Risk factors
Nulliparity
Family history (BRCA gene mutation)
NOT using oral contraceptives!

48. Ovarian Cancer Treatment: surgery, radiation, chemotherapy
Prognosis depends on stage
Cancer confined to the ovary: 5y survival 70%
Cancer through ovarian capsule: 5y survival 13%

49. Female Reproductive System Outline
Cervix
Uterus
Ovaries
Breast
Fibrocystic change
Tumors

50. Breast Many breast diseases present as lumps
Most lumps represent benign things…
…but a lump always needs to be evaluated
Ultrasound, mammography, fine needle aspiration, and biopsy are the usual methods

51. Most breast lumps are benign

52. Fibrocystic Change
Two kinds: nonproliferative and proliferative change
Cause: exaggeration of normal breast cycles
Rarely associated with increased cancer risk
Very common (present in most women at autopsy)
Called fibrocystic change, not fibrocystic disease

53. Fibrocystic Change Nonproliferative fibrocystic change
Increased stroma
Dilation of ducts, formation of cysts
Proliferative fibrocystic change
Hyperplasia of breast epithelium
If epithelium shows atypia, 5x ↑ risk of cancer

54. Fibrocystic change

55. Normal breast

56. Nonproliferative fibrocystic change

57. Proliferative fibrocystic change

58. Fibroadenoma Most common benign breast tumor Stimulated by estrogen
Peak incidence in 20s
Solitary, discrete, moveable mass
Fibrous tissue with compressed ducts and lobules

59. Fibroadenoma

60. Fibroadenoma

61. Breast Carcinoma 233,000 new cases / 40,000 deaths predicted in 2014
Most common, 2nd deadliest cancer in women
Lifetime risk: 1 in 8
75% of patients are >50
Rate was increasing but now stable

62. Breast Carcinoma Risk Factors
Age
Family history
Increased estrogen exposure
Obesity
Alcohol consumption
High-fat diet

63. Breast Carcinoma Family History
5-10% of all cases are hereditary
Worry if first degree relative with breast cancer
Most have BRCA-1 or BRCA-2 mutations
Tumor suppressor genes; help repair DNA
Genetic testing difficult
Most carriers get cancer by age 70

64. Breast Carcinoma Clinical Findings
If discovered by palpation
Solitary, painless, moveable mass
2-3 cm in diameter
Axillary nodes positive in 50% of patients
If discovered by mammography
1 cm in size
Axillary nodes positive in only 15% of patients
As disease progresses
Fixation to chest wall
Adherence to overlying skin
Peau d’orange

66. Advanced breast carcinoma: fixation to skin

67. Peau d’orange

68. Inflammatory breast carcinoma

69. Breast Carcinoma Histologic Types
Non-invasive
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS)
Invasive
Ductal
Lobular
Inflammatory
Others

70. Normal breast

71. Lobular carcinoma in situ

72. Invasive breast carcinoma

73. Low-grade invasive ductal carcinoma

74. High-grade invasive ductal carcinoma

75. Inflammatory breast carcinoma

76. Breast Carcinoma Prognostic Factors
Size of tumor
Lymph node involvement
Distant metastases
Grade of tumor
Histologic type of tumor

77. Sentinel node biopsy

78. TNM* staging system for breast cancer
Stage T N M
5-year survival
Stage 0
Stage I
Stage II
Stage III
Stage IV
DCIS
<2 cm
<5 cm
>5 cm
Any T
<3 4+ 1+
10+
Any N M0
skin or chest wall M1
92%
87%
75%
46%
13%
* Tumor (size), nodes (# positive), metastases