1. Female Reproductive Pathology
M. Kent Froberg, MD

2. Objectives
In this series of lectures we will ascend the female reproductive tract from the vulva to ovaries. At each anatomic site we will discuss the major clinical conditions including physiological, inflammatory, infectious and neoplastic disorders. Two hours will be devoted to sexually transmitted infections. There will be an emphasis on major characteristics of tumors at each site and pathogenic mechanisms of non-neoplastic disease.

3. VULVAR DYSTROPHY (leukoplakia)
Age: any but most menopausal
Gross: smooth-surfaced, dry, stiff, white, atrophic vulva
Micro:
lichen sclerosus: epidermal atrophy, dermal fibrosis
squamous hyperplasia: epithelium thick, hyperkeratotic (now called lichen simplex chronicus)
Effects: fissures, uclers, infections, pruritis; few  ca
Dx: biopsy
DDx: lichen sclerosus, lichen simplex chronicus, chronic dermatitis, Paget Disease, VIN, vulvar cancer

4. Vulvar Dystrophy (leukoplakia)
Dry-appearing, white patches on vulvar skin

5. Vulvar dystrophy is a common clinical entity with several etiologies making Bx of the affected area necessary.

6. Vulvar Dystrophy affecting perineal skin

7. One of the most common causes of leukoplakia is lichen sclerosus et atrophicus

8. Lichen sclerosus: atrophic epidermis and homogenized collagen within dermis

9. Mild inflammation in lichen sclerosis

10. Atrophic adenexal structures in lichen sclerosis

11. Lichen Simplex Chronicus with hyperkeratosis & epidermal hyperplasia

12. Vitiligo of vulva

13. VULVAR NEOPLASMS: BENIGN
Papillary hidradenoma
localized, benign, sweat gland tumor
structure: papillae of ductal lining cells
Condylomas (STD-related warts)
accuminatum: caused by human papilloma virus infection (HPV)  koilocytosis
lata: syphilitic wart

14. Papillary hidradenoma

15. Vulvar Papillary Hidradenoma with a lobular configuration of papillae covered by benign epithelium

16. Papillary Hidradenoma

17. Vulva: Carcinoma Precursor: vulvar intraepithelial neoplasia (VIN)
some pts present with vulvar dystrophy (leukoplakia)
Progressive grades of dysplasia I, II, III (III also called Bowen’s disease or carcinoma in situ)
HPV associated (especially types 16 & 18)
Concurrent vaginal and/or cervical CA in ~20%

18. Vulva: carcinoma Extramammary Paget disease
Presents as pruritic, red, crusted, well-delineated lesion usually on labia majora
Unlike Paget disease of breast - rarely associated with underlying invasive cancer
Confined to epidermis, hair follicles and sweat glands
Long survival, but may recur following surgical excision

19. Paget Disease of Vulva: tumor consists of intra-epidermal glandular cells

20. Paget Cells contain mucin

21. VULVA: CARCINOMA
Invasive carcinoma: may be preceeded by vulvar intraepithelial neoplasia (VIN)
squamous cell ca = 88%
spread  pelvic and inguinal nodes
Rx: radical resection vulva, pelvic + groin nodes
Prognosis:
no nodes + = 85% 5 yr survival
Groin nodes + = 66%
pelvic nodes + = 25%
Dx often delayed

22. Ulcerated Squamous Cancer

23. Exophytic Fissured Carcinoma

24. Vulvectomy

25. Nests of Squamous Cell Carcinoma with keratin whorls

26. Radical Vulvectomy for Squamous Cell Carcinoma

27. VULVAR CARCINOMA Verrucous squamous cell carcinoma:
rarely metastasizes
histologically bland & grossly mimics condyloma
Adenocarcinoma: few
from sweat glands?
Bartholin’s?
Melanoma:
5% of vulvar cancer
delay in Dx  30% 5 yr survival

28. Verrucous Carcinoma: has gross appearance of condyloma

29. Verrucous Carcinoma of Vulva

30. VULVA: BARTHOLIN’S GLAND
Normal:
columnar-lined
mucus-secreting cyst
narrow neck
Chronic inflammation  scarring  obstructs neck  cyst
Acute inflammation (often gonococcus, chlamydia)  abscess

31. Swollen Bartholin’s Gland

32. Bartholin’s Cyst

33. Inflamed Bartholin’s Gland with squamous metaplasia

34. Wall of Bartholin’s cyst with acute & chronic inflammation

35. Bartholin’s Abscess

36. VULVO-VAGINAL INFLAMMATION
Gonorrhea in children
Trichomonas (strawberry mucosa — red)
Moniliasis (candidiasis): white patches
Herpes (vesicles)
Senile vaginitis (drynessulcers, fissures)

37. Candidiasis with satellite lesions

38. Candida
White fungal patches on vulva and perineum

39. Candida yeast forms within keratin layer

40. Moist, inflamed vagina from Trichomoniasis

41. Wet mount of Trichomonas vaginalis (flagellated protozoan): is an STD

42. VAGINA: CONGENITAL LESIONS
Imperforate hymen:
Hematocolpos (blood filling uterus)
reflux
Septate (“double”) vagina

43. VAGINA: VAGINAL ADENOSIS
Islands of cervical glands beneath squamous ectocervix
cervical eruption
Cause:
rarely congenital
most = maternal exposure to diethylstilbesterol (DES)
Asymptomatic but 0.1%  adenocarcinoma

44. Adenosis may occur after DES or estrogen exposure during early fetal development

45. Vaginal adenosis

46. Adenosis

47. Tuboendometrial glands in vaginal adenosis

48. Red, granular focus of vaginal adenosis within squamous mucosa

49. VAGINAL: CANCER (1)
Types: squamous cell carcinoma; adenocarcinoma; sarcoma botryoides; yolk sac tumor
Squamous cell carcinoma:
precursors: ca cervix or vulva; intraepithelial neoplasia (VIN)
spread: upper  pelvic nodes, lower  inguinal
staging: like cervix
prognosis: stage 1 = 80% 5 yr; 3-4 = <20%
Adenocarcinoma: clear cell type = DES-related; young

50. Uterus
Cervix
Clear Cell Adenocarcinoma of vagina (arrow)

51. Glycogen filled clear cells of Clear Cell Adenocarcinoma

52. VAGINA: CANCER (2) Embryonic rhabdomyosarcoma (sarcoma botryoides)
age: <5yr
gross: rounded, grape-like (Greek: Botrys = grape) bulky mass
histology: small blue cell tumor may show myoblastic or strap cells; striations in some
behavior: locally destructive; large ones metastasize
Prognosis good if Rxed early

53. Protruding vaginal polypoid mass of Embryonal Rhabdomyosarcoma

54. Polypoid masses of Sarcoma Botryoides (embryonal rhabdomyosarcoma)

55. Cambian layer of sarcoma botryoides underlying vaginal epithelium

56. Muscle-like cells and rhabdomyoblasts in rhabdomyosarcoma

58. Cross striations may be present in cells of rhabdomyosarcoma (arrow)

59. VAGINA: CANCER (3) Endodermal sinus (yolk sac) tumor
like same tumor in ovary
histo: sheets & Schiller-Duval body (central blood vessel surrounded by 2 layers of germ cells)
synthesizes alpha fetoprotein (hyaline droplets that stain + by IHC; also  in blood) and alpha-1-trypsin
prognosis: awful

60. Schiller-Duvall bodies of Endodermal Sinus (Yolk Sac) Tumor