Pathology Thread

II. Inflammatory and Infectious Diseases

Objectives

After completing this section you will be able to:

• list the infectious diseases involving the cervix
• specify the etiologic agents and mode of transmission
• describe/recognize clinical lesions
• describe/identify characteristic histologic features
• state clinical behavior/complications

1. Noninfectious (Nonspecific) Cervicitis

This is inflammation of the cervix caused by chemical (e.g. douche, deodorant) or mechanical (e.g. tampon, diaphragm) irritation. It is often acute but may be chronic.

Clinical appearances

Noninfectious cervicitis is often asymptomatic. The cervix appears red and swollen.

Histology

The histologic features are nonspecific. The inflammatory infiltrate may comprise neutrophils or plasma cells and lymphocytes or a combination of these cells.

Squamous metaplasia of the endocervical glandular epithelium is common in chronic cervicitis. Often some of the mucous glands are obstructed and dilate to form mucus-filled cysts called nabothian cysts.

Nonspecific cervicitis.

2. Clamydia trachomatis Cervicitis

Clamydia trachomatis is an obligate, gram-negative intracellular pathogen of columnar epithelial cells that causes venereal infections. Clamydial cervicitis is caused by serotypes D through K and is the most common sexually transmitted disease in the developed countries. It may coexist with Neisseria gonorrhoeae infection.

Question: Why is C. trachomatis an obligate intracellular organism?

Clinical appearances

The disease may be symptomatic or asymptomatic. In symptomatic cases there is a mucopurulent cervical discharge with a reddened, congested and edematous cervix. It may be associated with urethritis in the patient and/or partner.

Histology

The subepithelial connective tissue of the endocervix shows a nonspecific, diffuse dense infiltrate of lymphocytes and plasma cells and also macrophages. Occasionally, many subepithelial lymphoid follicles with germinal centers, a condition called follicular cervicitis, are present. Follicular cervicitis is semi-specific for clamydial cervicitis. Intracytoplasmic inclusions in endocervical glandular or metaplastic epithelium may be seen in some cases but is not specific for diagnosis. Diagnosis is confirmed by demonstrating the organisms in glandular epithelial cells by immunohistochemical or immunofluorescent techniques or by culture.

Complications

The cervix serves as a nidus for ascending infection. Endometritis occurs in 40% and salpinghitis in 11% of cases. These are often subclinical. Postinfectious sequelae include generalized infection of the pelvic adnexal organs (pelvic inflammatory disease) and tubal blockage with infertility or ectopic pregnancy. Infants born to mothers with C. trachomatis cervicitis may develop inclusion conjunctivitis or neonatal pneumonia.

3. Herpes simplex virus (HSV) Cervicitis

See section on Vulva.

Lesions involving the ectocervix are usually asymptomatic or cause profuse watery discharge. Cervical involvement can be detected in 90% of women with primary genital HVS infections. However, only up to 20% of women with recurrent infections have cervical involvement. Ulceronecrotic lesions are observable on the cervix. In some cases the lesions are so extensive as to be confused clinically with carcinoma.

Question: How is HSV cervitis diagnosed?

4. Human papilloma virus (HPV) Infection

HPV infection of the cervix is common. Over 20 serotypes infect the female genital types. They cause a variety of lesions with the different serotypes associated with different lesions.

Condyloma. This develops in the squamous epithelium of the ectocervix and in foci of squamous metaplasia in the endocervix. The lesions may be flat or exophytic condylomma acuminatum. More than 90% are flat.

Flat condylomas are not apparent grossly unless the cervix is painted with acetic acid and examined colposcopically, when they appear as sharply demarcated, white, slightly raised plaques.

Exophytic condyloma acuminatum can be caused by any HPV serotype but more commonly by types 6 and 11. It appears white, the degree of whiteness depending on the thickness of surface hyperkeratosis. Many small, maculo-papular, slightly raised lesions may be seen in some cases.

Cervical condyloma. Note white macular lesions.

Mild dysplasia is usually caused by "low risk" HPV serotypes, 6 and 11 (see CIN).

High- grade dysplasia is caused by "high (16 and 18) and moderate (31,33,35) risk" HPV serotypes (see CIN).

Histology

In flat condyloma, the epithelium is hyperplastic and, in absence of neoplastic change, the cells show orderly differentiation with regular nuclear features. Koilocytes are present in the upper and middle layers of the epithelium. The presence of mild atypical cellular changes correlates strongly with infection by HPV serotypes 6 and 11. High and inter-mediate risk serotypes are associated with more severe grades of atypia and invasive carcinoma.

HPV with extensive koilocytosis.

HPV with CIN 1

The histologic features of cervical condyloma acuminatum are identical to those seen in the vulva.

Clinical behavior

HPV infection is associated with increased risk of subsequent cervical cancer. The entire lower genital tract is a target area for HPV infection and so long-term follow-up with attention to the cervix, vagina and vulva is necessary.