Session 32 Female Reproductive System Pathology

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Lecture Notes

Session 32: Female reproductive system pathology

Felician Sikujua (MD)

Learning tasks

At the end of this session, students are expected to be able to:

Explain pathologies of vulva.

Explain pathologies of vagina.

Explain pathologies of cervix.

Explain pathologies of uterus.

Explain pathologies of fallopian tubes.

Explain pathologies of ovaries.

Diseases of Vulva:Vulvitis

Most common causes of vulvitis is reactive inflammation to exogenous stimulus.

Contact irritant eczymatous dermatitis.

Erythematous weeping and crusting papules and plaques.

Urine, soaps, detergents, antiseptics, deodorants, alcohol.

Allergic dermatitis.

Similar clinical appearance.

Perfumes, additives in creams, lotions, and soaps.

Scratching-induced trauma secondary to associated intense “itching” (pruritus) often exacerbates the primary condition.

Vulvitis cont…

Vulvitis also may be caused by infections (STIs).

The most important of these infectious agents are

Human papillomavirus (HPV).

Herpes simplex virus (HSV-1 or -2).

Neisseria gonorrhoeae.

Treponema pallidum.

Candida albicans.

An important complication of vulvitis is obstruction of the excretory ducts of Bartholin glands.

This blockage may result in painful dilation of the glands (a Bartholin cyst) and abscess formation.

Non-neoplastic epithelial disorders of Vulva

Lichen sclerosus

Characteristics

Atrophic epithelium.

Thinning of the epidermis.

Hydropic degeneration of the basal cells.

Dermal fibrosis.

Mononuclear inflammatory cells.

Leukoplakia area.

Development of squamous cell carcinoma.

Lichen simplex chronicus

Characteristics

Epithelial thickening (particularly of the stratum granulosum).

Hyperkeratosis.

Increased mitotic activity is seen in the basal and suprabasal layers.

Leukocytic infiltration of the dermis.

Leukoplakia area

Tumors of the vulva

Condyloma

Any warty lesion of the vulva.

Condylomas can occur anywhere on the anogenital surface and more often as multiple lesions.

Two (2) distinctive forms.

Condylomata lata

Occurs in secondary syphilis (Treponema pallidum).

Condylomata acuminata

Caused by Human papilloma virus (HPV 6, 11).

Koilocytosis is present.

Carcinoma of the Vulva

Occurs mostly in women older than age 60.

90% are squamous cell carcinomas (SCC).

Other tumors: adenocarcinoma and basal cell carcinomas.

Two (2) distinct forms of vulvar SCC

The first form

Less common form.

Related to high-risk HPV strains (HPV 16 and 18)

A second form

Often is preceded by lichen sclerosus.

Diseases of Vagina:Vaginitis

It is associated with production of a vaginal discharge (leukorrhea).

A large variety of organisms have been implicated, including bacteria, fungi, and parasites.

In adults, primary gonorrheal infection of the vagina is uncommon.

The frequently offending microorganisms are Candida albicans and Trichomonas vaginalis.

Vaginitis cont…

Many are normal commensals (flora) that become pathogenic only in the setting of:

Diabetes mellitus.

Systemic antibiotic therapy.

Causes disruption of normal microbial flora.

Immunodeficiency.

Pregnancy.

Recent abortion.

Candidal (monilial) vaginitis is characterized by a curdy white discharge.

Trichomonas vaginalis produces a watery, copious gray-green discharge.

Malignant neoplasms of Vagina

Squamous cell carcinoma of the vagina

Extremely uncommon cancer.

Usually occurs in women older than 60 years of age

Risk factors similar to those of carcinoma of the cervix.

Vaginal intraepithelial neoplasia is a precursor lesion.

Invasive squamous cell carcinoma of the vagina is associated with the presence of HPV.

Clear cell adenocarcinoma

A very rare tumor associated with vaginal adenosis.

Occurs to young women whose mothers took diethylstilbestrol during pregnancy.

Diseases of Cervix:Cervicitis

Associated with a purulent vaginal discharge (leukorrhoea).

Normal vaginal flora including Streptococci, Staphylococci, Enterococci, and Escherichia coli is implicated.

Also sexually transmitted microorganisms Chlamydia trachomatis, Ureaplasma urealyticum, T. vaginalis, Candida spp., Neisseria gonorrhoeae, HSV-2, and certain types of HPV causes cervicitis.

Chlamydia trachomatis is the most common of these pathogens.

Neoplasia of the Cervix

Most tumors of the cervix are of epithelial origin.

Caused by oncogenic strains of human papillomavirus (HPV 16, 18).

Normally during development, the columnar, mucus-secreting epithelium of the endocervix is joined to the squamous epithelial covering of the exocervix at the cervical os.

With the onset of puberty, the squamocolumnar junction (transformation zone) undergoes eversion, causing columnar epithelium to become visible on the exocervix.

Risk factors for the development of CIN and invasive carcinoma

HPV is detectable in nearly all cases of cervical intraepithelial neoplasia (CIN) and cervical carcinoma.

Important risk factors for the development of CIN and invasive carcinoma thus are directly related to HPV exposure and include:

Early age at first intercourse

Multiple sexual partners

Male partner with multiple previous sexual partners

Persistent infection by high-risk strains of papillomavirus (16, 18, 31, 45).

Invasive Carcinoma of the Cervix

The most common cervical carcinomas are

Squamous cell carcinomas (most common).

Adenocarcinomas.

Mixed adenosquamous carcinomas

Small cell neuroendocrine carcinomas.

All of these types of carcinomas are caused by HPV.

Squamous cell carcinoma requires HPV infection as well as mutations in genes.

Risk factors for progression of CIN to invasive carcinoma include cigarette smoking and human immunodeficiency virus (HIV) infection.

Endocervical polyp

Benign polypoid masses protrude from endocervical mucosa (sometimes through the exocervix).

They can be as large as a few centimeters.

Soft and smooth, glistening surface with cystically dilated spaces filled with mucinous secretions.

Stroma is edematous and contain mononuclear cells.

Superimposed chronic inflammation may lead to squamous metaplasia of the overlying epithelium and ulcerations.

They may bleed but have no malignant potential.

Diseases of Uterus:Endometritis

Can be acute or chronic depending on whether a neutrophilic or a plasma cells response predominates.

Endometritis often is a consequence of PID.

It is frequently caused by Neisseria gonorrhoeae or Chlamydia trachomatis.

Tuberculosis causes granulomatous endometritis.

Histologic examination

Neutrophilic infiltrate in the superficial endometrium and glands

Coexisting with a stromal lymphocytic infiltrate.

Prominent lymphoid follicles are more commonly seen in chlamydial infection.

Endometritis cont…

Endometritis also may be due to

Retained products of conception, subsequent to miscarriage or delivery.

Presence of a foreign body such as an intrauterine device.

Retained tissue or foreign bodies act as a nidus for ascending infection by vaginal or intestinal tract flora.

Removal of the offending tissue or foreign body typically results in resolution.

Clinically, presents with fever, abdominal pain, and menstrual abnormalities.

There is risk of infertility and ectopic pregnancy.

Adenomyosis

Adenomyosis refers to the growth of the basal layer of the endometrium down into the myometrium.

Nests of endometrial stroma, glands, or both, are found deep in the myometrium interposed between the muscle bundles.

Due to metaplasia or oestrogenic stimulation due to endocrine dysfunction of the ovary.

Presents with menorrhagia, dysmenorrhea, pelvic pain.

No cyclic bleeding.

Endometriosis

Presence of endometrial glands and stroma in a location outside the endomyometrium.

Often involves pelvic structures (ovaries, pouch of Douglas, uterine ligaments, tubes, and rectovaginal septum).

Endometriosis almost always contains functioning endometrium, which undergoes cyclic bleeding.

In contrast with adenomyosis.

When the ovaries are involved, the lesions may form large, blood-filled cysts that turn brown (chocolate cysts) as the blood ages.

Abnormal uterine bleeding

Types of abnormal uterine bleeding are such as

Menorrhagia.

Metrorrhagia.

Postmenopausal bleeding.

Common causes include endometrial polyps, leiomyomas, endometrial hyperplasia, endometrial carcinoma, and endometritis.

The probable cause of uterine bleeding in any given case depends somewhat on the age of the patient.

Abnormal uterine bleeding cont…

Abnormal bleeding from the uterus in the absence of an organic uterine lesion is called dysfunctional uterine bleeding (DUB).

Diagnosis of exclusion.

Causes of abnormal uterine bleeding, both dysfunctional and secondary to an organic lesion can be put into four (4) groups:

Failure of ovulation.

Inadequate luteal phase.

Contraceptive-induced bleeding.

Endomyometrial disorders.

Endometrial hyperplasia

An excess of estrogen relative to progestin, if sufficiently prolonged or marked, can induce exaggerated endometrial proliferation (hyperplasia).

An important precursor of endometrial carcinoma.

The severity of hyperplasia is correlated with the level and duration of estrogen excess.

Hyperplasia is classified based on

Architectural crowding (simple versus complex)

Presence or absence of cytologic atypia.

The risk of developing carcinoma is related to the presence of cellular atypia.

Endometrial carcinoma

Appears between the ages of 55 and 65 years.

Comprise two (2) distinct kinds of cancer

Endometrioid carcinoma of the endometrium(common).

Serous carcinoma of the endometrium.

Endometrioid cancers arise in association with estrogen excess and endometrial hyperplasia in perimenopausal women.

Serous cancers arise in the setting of endometrial atrophy in older postmenopausal women.

Less common

Endometrial polyps

These sessile, usually hemispheric lesions.

Larger polyps may project from the endometrial mucosa into the uterine cavity.

Composed of endometrium resembling the basalis, frequently with small muscular arteries.

Some glands have a normal endometrial architecture, but more often they are cystically dilated.

Common during menopause.

Their clinical significance lies in

Abnormal uterine bleeding.

Risk of giving rise to a cancer (rare).

Leiomyoma

Benign tumors that arise from the smooth muscle cells in the myometrium.

Because of their firmness, they often are referred to clinically as fibroids.

The most common benign tumor in females

Affecting women of reproductive age.

More frequent in blacks than in whites.

Estrogens and possibly oral contraceptives stimulate the growth of leiomyomas.

These tumors shrink postmenopausally.

Morphology: Leiomyomas

Sharply circumscribed, firm gray-white masses with a characteristic whorled cut surface.

They may occur singly, but more often multiple tumors are scattered within the uterus.

The presence of multiple lesions does not increase the risk of malignancy.

Leiomyomas almost never transform into sarcomas.

On histologic examination: Bundles of smooth muscle cells mimicking the appearance of normal myometrium.

Foci of fibrosis, calcification, and degenerative softening may be present.

Morphology: Leiomyomas cont…

Leiomyosarcoma

Arise de novo from the mesenchymal cells of the myometrium, not from preexisting leiomyomas.

They are almost always solitary.

Most often occur in postmenopausal women.

Metastasize typically to the lungs,

Soft, hemorrhagic, necrotic masses.

The histologic appearance varies widely.

The diagnostic features of overt leiomyosarcoma include tumor necrosis, cytologic atypia, and mitotic activity.

Diseases of Fallopian tubes

The most common disorder of the fallopian tubes is inflammation (salpingitis)

Component of pelvic inflammatory disease.

Less common abnormalities are

Ectopic (tubal) pregnancy.

Endometriosis.

Primary tumors (rare).

Salpingitis

Inflammations of the fallopian tube are almost always microbial in origin.

These microbes are

Chlamydia.

Mycoplasma hominis.

Coliforms.

Streptococci.

Staphylococci.

Tuberculous salpingitis is far less common.

Clinical course: Salpingitis

Fever, lower abdominal or pelvic pain, and pelvic masses are seen in salpingitis.

Adherence of the inflamed tube to the ovary and adjacent ligamentous tissues may result in a tuboovarian abscess, referred to as a tuboovarian complex when infection subsides.

Even more serious are adhesions of the tubal plicae, which are associated with increased risk of tubal ectopic pregnancy.

Damage to or obstruction of the tubal lumina may produce permanent sterility.

Diseases of Ovaries

Diseases affecting ovaries include

Follicle and Luteal cysts.

Polycystic ovarian syndrome.

Inflammatory conditions (oophritis).

Ovarian tumors.

Follicle and luteal cysts

Common.

Physiological.

Originate from

Unruptured Graafian follicles

Follicles that have ruptured and then become immediately sealed.

Multiple.

Develop subjacent to the serosal covering of the ovary.

Follicle and luteal cysts

They typically are small (1 to 1.5 cm in diameter) and are filled with clear serous fluid.

Can become sufficiently large (4 to 5 cm) to produce palpable masses and pelvic pain.

When small, they are lined by granulosa lining cells or luteal cells, but as fluid accumulates, pressure may cause atrophy of these cells.

Sometimes these cysts rupture, producing intraperitoneal bleeding and peritoneal symptoms (acute abdomen).

Polycystic ovarian disease

Formerly called Stein-Leventhal syndrome) is a disorder in which multiple cystic follicles in the ovaries produce excess androgens and estrogens.

After menarche in teenage girls or young adults with

Oligomenorrhea.

Hirsutism.

Infertility.

Obesity.

The ovaries are usually twice the normal size.

Histologic examination reveals a thickened, fibrotic ovarian capsule overlying innumerable cystic follicles

Tumors of the Ovary

Tumors of the ovary are amazingly varied.

This diversity is attributable to the presence of three cell types in the normal ovary:

Multipotent surface (coelomic) epithelium.

Totipotent germ cells.

Sex cord– stromal cells.

Neoplasms of surface epithelial origin account for the great majority of primary ovarian tumors.

Germ cell and sex cord–stromal cell tumors are much less frequent.

Risk factors for ovarian cancer

Important risk factors for ovarian cancer include

Nulliparity.

Family history.

Germline mutations in certain tumor suppressor genes.

Smoking cigarette.

There is a higher incidence of carcinoma in unmarried women and married women with low parity.

Prolonged use of oral contraceptives somewhat reduces the risk.

Key points

Leukorrhoea is the commonest presenting feature in cervicitis.

High-risk HPV infection (HPV 16 and 18) is the most important risk factor for cervical carcinoma.

Chocolate cysts are seen in endometriosis.

Endometrial hyperplasia transforms to endometrial carcinoma.

Leiomyomas (fibroids) affect commonly blacks and women of reproductive age.

Salpingitis is the commonest disease of oviducts.

Epithelial tumors are the most common malignant ovarian tumors.

Review questions

List five (5) predisposing factors for vaginitis.

Outline five (5) risk factors for cancer of the cervix.

Mention three (3) complications of salpingitis.

List four (4) features of polycystic ovarian syndrome.

Mention four (4) risks factor for Ovarian cancer.

References

Goljan E.;(2007): Rapid Review Pathology (2th Ed.) Elsevier Saunders, USA. Pg. 448-472.

Kumar V. ; Abbas A. K. ; Aster J. C.;(2013): Robbins and Contran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, USA. Pg. 681-700.

Mohan H.;(2010): Text book of Pathology (6th Ed.) Jaypee Brothers Medical Publishers, India. Pg. 721-750.

Xiu P.;(2012): Crash Course Pathology (4th Ed.) Elsevier Saunders, USA. Pg. 201-210.

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Session 32 Female Reproductive System Pathology

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