Benign Cervical Lesions

By 5 weeks' gestational age, the wolffian (ie, mesonephric) and the müllerian (ie, paramesonephric) ducts have formed from intermediate mesoderm. In the absence of testosterone and müllerian inhibitory substance, the mesonephric ducts regress and the paramesonephric ducts continue to form the female reproductive structures with fusion of the distal portions of the paramesonephric ducts to give rise to the uterine fundus, the cervix, and the upper vagina. ^[1] These developmental changes are genetically controlled in large part by a series of complex transcriptional signaling pathways including Wnt signaling, Hox genes, and many others. In a female fetus, the wolffian duct disappears except for nonfunctional vestiges. The müllerian duct is lined by a columnar epithelium. This includes the entire cervix and upper vagina to the vaginal plate (ie, sinovaginal bulb). Through a process of squamous metaplasia, the vagina and a variable portion of the ectocervix become covered with squamous epithelium. This process is complete by the fifth month of pregnancy.

The cervix (Latin for neck) is the inferior part of the uterus protruding into the vagina.

Gross anatomy

The cervix measures 2.5-3 cm in diameter and 3-5 cm in length. The normal anatomic position of the cervix is angulated slightly downward and backward. Inferiorly, the cervix projects into the vagina as the portio vaginalis with the opening of the cervical canal into the vagina called the external cervical os (Latin for mouth). The external os is usually small and round in nulliparous women but can be seen as a transverse slit in those who have had cervical dilation during labor. The anterior and posterior fornices delimit the portio (exocervix). The cervical canal measures approximately 8 mm wide and contains longitudinal ridges. The opening of the cervical canal into the uterus is called the internal cervical os. The area between the endocervical and endometrial cavity is called the isthmus or lower uterine segment.

The lymphatic drainage of the cervix is first to the parametrial nodes, then to the obturator, internal iliac, and external iliac nodes. Secondary drainage is to the presacral, common iliac, and para-aortic lymph nodes.

The innervation of the cervix is from the Frankenhãuser plexus, a terminal part of the presacral plexus. The nerves enter the lower uterine segment and upper cervix on either side and form 2 lateral semicircular plexuses. The major blood supply is from the descending branch of the uterine artery. Also contributing is the cervical branch of the vaginal artery. The venous return mirrors the arterial blood supply.

Microscopic anatomy

Microscopically, the cervical stroma is composed of an admixture of fibrous, muscular (15%), and elastic tissue. The epithelium is squamous on the ectocervix and columnar in the endocervix. The exposed (ie, vaginal) portion of the cervix is lined by nonkeratinizing stratified squamous epithelium that becomes continuous with the vaginal epithelium. This is referred to as the native portio epithelium and is replaced every 4-5 days while glycogen stores respond to hormonal changes in estrogen and progesterone. In postmenopausal women, the squamous epithelium is atrophic with little or no glycogen. Tissue alterations due to these atrophic changes, trauma, erythema, and microvascularization can be confused with cervical intraepithelial neoplasia.

The mucosa of the cervical canal (endocervix) is composed of a single layer of mucin-secreting columnar epithelium, which covers the surface and the underlying glandular crypts. Isolated neuroendocrine epithelial cells of argentaffin type or argyrophil type are admixed with the normal endocervical cells. Under normal conditions, mitotic figures are rarely identified in endocervical epithelium. True lymphoid follicles, with or without germinal centers, are encountered in the stroma of both the ectocervix and endocervix. During pregnancy, a marked increase occurs in the vascularity and edema within the cervical stroma and an inflammatory infiltrate is present. ^[2]

Squamocolumnar junction

The squamocolumnar junction is the border between the squamous epithelium of the ectocervix and the columnar epithelium of the endocervix. Just distal to the squamocolumnar junction, an area of immature squamous metaplastic epithelium is present. Trauma, chronic irritation, and cervical infections play a role in the development and maturation of the squamous epithelium of the cervix. Immature squamous metaplasia shares biochemical and immunohistochemical features of both mature squamous epithelium and columnar mucinous epithelium.

The transformation zone

The transformation zone is a dynamic area, usually located on the ectocervix. At times, the distal edge of the transformation zone extends into the upper vagina. The transformation zone, by definition, is the area between the original squamocolumnar junction and the current squamocolumnar junction. The transformation zone is that portion of the cervix that originally was columnar epithelium and through a process of squamous metaplasia is now squamous epithelium. Squamous metaplasia occurs continuously; however, this process is most active during fetal development, around the time of menarche, and during pregnancy. Local hormonal changes, as reflected by vaginal pH, influence this process.

In newborns and young females, the endocervical tissue tends to roll out from the cervical os; this is called cervical eversion (ie, ectropion), and corresponds to the original squamocolumnar junction. In a normal transformation zone, one can find remnants of gland openings and nabothian cysts. In postmenopausal women, the squamocolumnar junction frequently is located within the cervical canal. In this position, it is not visualized through speculum examination or colposcopy, even when using an endocervical speculum. Colposcopy, or microscopically guided visualization of the cervix, is frequently unsatisfactory because of the inability to visualize the squamocolumnar junction in its entirety. Understanding the transformation zone is of utmost importance because cervical cancer and its precursors typically begin within the transformation zone.

Cervical mucus responds to hormonal stimulation. Under the influence of estrogen, the cervical mucus is profuse, watery, and alkaline. The rich concentration of sodium chloride and potassium are responsible for ferning. The degree of ferning reflects estrogen levels. ^[3] After ovulation and under influence of progesterone, the cervical mucus is thick, scant, and acidic and contains numerous leukocytes. In pregnancy, the cervical mucus is even thicker and more tenacious. It is rich in leukocytes and forms a mucous plug that obliterates the cervical canal. ^[4] During pregnancy, during the postpartum state, and in women who are on progestin therapy, microglandular hyperplasia may occur. This is discussed in detail later (see Microglandular hyperplasia in the Benign Tumors section). Decidual changes within the cervical stroma can also occur during pregnancy and high-dose progestin therapy.

Congenital anomalies involving the cervix reflect only the lower part of the spectrum of congenital anomalies involving the müllerian system. The cervix has 3 types of anomalies: fusion abnormalities, congenital absence, and changes due to in utero exposure to diethylstilbestrol (DES) and other nonsteroidal estrogens. Müllerian congenital abnormalities are frequently associated with urinary tract anomalies because of associated mesometanephric duct developmental defects. ^{[5, 6]}

Fusion anomalies

A failure to fuse or incomplete fusion of the müllerian ducts results in duplication of the vagina, cervix, or uterus. Failure of fusion of the distal müllerian duct can result in any of the anomalies discussed below.

Uterus didelphys results from a complete lack of fusion of the müllerian ducts. Duplication of the vagina, cervix, and/or uterus occurs. A longitudinal vaginal septum is present, with 2 separate cervices and 2 separate endometrial cavities.

With septate cervix, the appearance is that of 1 cervix with 2 separate cervical openings. The septum may be partial. The gross appearance is 1 of 2 separate cervices but 1 endometrial cavity. On the other hand, the septum may extend through the entire length of the uterus, with 2 separate endometrial cavities. Depending on the shape of the uterine fundus, the anomaly is either a septate uterus or an arcuate uterus. Laparoscopy is necessary to distinguish between these 2 anatomic variations.

Congenital absence or hypoplasia of the cervix

Congenital absence of the cervix usually occurs as part of the syndrome of müllerian agenesis, also known as Mayer-Rokitansky-Kuster-Hauser syndrome. This syndrome occurs in approximately 1 per 4000 female births.

Women with müllerian agenesis typically have a blind vagina and normal ovaries. Approximately one third of patients have urinary tract anomalies, and 12% have skeletal anomalies, usually involving the spine. Imaging of these structures should be part of the evaluation. ^[7]

In women with partial müllerian agenesis, a uterine bud or fundus may be present without a cervix and proximal vagina. If endometrium is present in this uterine bud, hematometra occurs at puberty, producing cyclic abdominal pain. Obstructive conditions from absent or hypoplastic cervices may occur and require surgical intervention if hematometra or pyometra occurs. Vaginal patency has been surgically created in a few patients, and pregnancy has been reported in absence or atresia of the cervix via transmyometrial or transtubal embryo transfer. ^[8]

In utero exposure to diethylstilbestrol and other nonsteroidal estrogens

The use of diethylstilbestrol or DES, which initially was prescribed for thousands of women to prevent miscarriage, was discontinued in the 1970s when epidemiologic association of in utero exposure to DES with clear cell vaginal adenocarcinoma in the developing fetus (1 case in 1000-2000 exposed female fetuses) was discovered. Changes associated with in utero exposure to DES and other nonsteroidal estrogens are less commonly encountered currently. However, unique anomalies of the müllerian system are present in women exposed to DES.

The classic anomaly is a hypoplastic T-shaped uterus, referring to the T shape of the endometrial cavity. Defects limited to the cervix, in addition to hypoplastic cervix, include local interesting gross and colposcopic findings. These findings include the so-called cockscomb cervix, cervical rings, cervical collars, and cervical hoods. The cockscomb cervix refers to the abnormal stromal development causing the epithelium to be thrown into firm transverse ridges in the anterior vaginal fornix, including the upper ectocervix. Vaginal adenosis and other benign lesions are more prevalent (approximately 80%) in women exposed to DES and other nonsteroidal estrogens. The squamocolumnar junction may even be in the vaginal fornix.

Cervical insufficiency in pregnancy with recurrent loss and/or infertility are potential problems in females exposed to DES. ^[9]

Prevalence and Tissue Response

Inflammation of the cervix is extremely common. Chronic inflammation is present in the cervix of almost every sexually active woman. On a microscopic level, regardless of the etiology, the tissue response of the cervix is limited to inflammation and repair. ^[10] For a more complete review of infectious and noninfectious cervicitis, see Medscape Reference article Cervicitis.

Infectious Cervicitis

Susceptibility of the cervix to bacterial infection depends on the virulence of the organism, the epithelial integrity, and the vaginal pH. Infections of the endocervical canal include infection with Neisseria gonorrhoeae and Chlamydia trachomatis. Organisms infecting the portio of the cervix can produce either exophytic or ulcerative lesions. These include human papilloma virus (HPV), herpes simplex virus (HSV), Treponema pallidum, Haemophilus ducreyi, and donovanosis.

Infections of the endocervical canal (mucopurulent cervicitis)

Infection with C trachomatis or N gonorrhoeae requires no predisposing factor and primarily depends on the size of the inoculum.

Mucopurulent secretions have been reported in more than 60% of women with cervical chlamydial infections. However, mucopurulent discharge is present in 12% of women with no cervical pathology. Yellow mucopurulent discharge collected from the endocervix and visualized on a white cotton-tipped applicator may also correlate with chlamydia, gonorrhea, trichomonads or HSV infections. In published studies, the sensitivity, specificity, and positive predictive values from clinical evaluation of the discharge have been quite variable. Thus, the color and consistency of the discharge alone is not enough to make a specific diagnosis. ^[11]

Because mucopurulent cervicitis may be a sign of upper genital tract disease, women presenting with mucopurulent cervicitis should be tested for gonorrhea and chlamydia with the most sensitive and specific test available. ^{[12, 13]} They should also be evaluated for bacterial vaginosis and trichomoniasis. HSV should be selectively tested for if there is clinical suspicion and identifiable lesions.

Gram stain findings of gram-negative intracellular diplococci within the cytoplasm of neutrophils are highly specific for gonorrhea but can be identified in only 50-60% of women with gonococcal infections. On occasion, cervical cytology identifies inclusion-containing vacuoles in endocervical or metaplastic cells. The presence of these inclusions correlates well with C trachomatis infection. Nucleic Acid Amplification Tests (NAATs) are currently the most sensitive tests available for both chlamydia and gonorrhea. In women, they are collected from the first catch urine samples or from self or clinician collected vaginal swabs. ^[14] The best guide to therapy for endocervicitis is identification of the specific microbiologic agent.

United States Preventative Services Task Force (USPSTF) chlamydia screening guidelines for women are as follows: ^[15]

• Screen for chlamydia infection in all sexually active nonpregnant women age 24 and younger and in older nonpregnant women who are at increased risk.

• Screen all pregnant women age 24 and younger and older pregnant women who are at increased risk.

• Do not routinely screen women age 25 and older, regardless of pregnancy status, if they are not at increased risk.

Treatment for mucopurulent cervicitis after identifying the causative organism is outlined in Table 1. The US Centers for Disease Control and Prevention do not recommend a test of cure in uncomplicated gonorrheal or chlamydial infection when treated with any of the outlined regimens, unless symptoms persist. Pregnant women should not be treated with quinolones or tetracyclines. ^[16]

In April 2007, the Centers for Disease Control and Prevention (CDC) updated treatment guidelines for gonococcal infection and associated conditions. Fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the United States ^[17] . The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP). The data from GISP showed the proportion of fluoroquinolone-resistant gonorrhea (QRNG) cases in heterosexual men reached 6.7%, an 11-fold increase from 0.6% in 2001. This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 125 mg IM once as a single dose). Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented.

Table 1. Treatment for Mucopurulent Cervicitis (Open Table in a new window)

Infections involving the portio of the cervix

Infections involving the portio of the cervix are as follows:

• Human papilloma virus (HPV)

  • Currently, more than 100 serotypes of HPV are described and more than 40 serotypes infect mucosal surfaces. The typical exophytic warts that present on the vulva, vagina, and cervix are type 6 or type 11. Types 16, 18, 31, 33, and 35 are more commonly associated with flat warts and have an epidemiologic link to cervical intraepithelial neoplasia or CIN ^{[18, 19]} . Kits are available that classify HPV lesions as either benign (ie, 6 or 11) or at risk (ie, 16, 18, 31, 33, and 35). Currently, for reflex HPV testing of thin layer cervical cytology, 14 different oncogenic HPV types are tested: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. Co-infections with multiple serotypes occur in 5-20% of those infected with HPV. ^[20]

  • Approximately 15% of Americans, or 20 million people, are currently infected with HPV; half of these are sexually active adolescents and young adults aged 15-24 years. ^[20]

  • HPV can infect the ectocervix and can cause warty lesions similar to those seen in the vagina or on the vulva. However, the lesions on the cervix typically are flat, macular or papular lesions that become more visible to the naked eye when swabbed with 3-5% acetic acid. The acetic acid causes cellular dehydration. The resulting increase in nuclear density appears clinically as a transient white lesion. The term aceto-white describes this finding. In addition to HPV, squamous metaplasia and cervical intraepithelial neoplasia can also appear aceto-white.

  • HPV lesions tend to have indistinct and feathered borders, and the lesions may appear broken or flocculated. Unlike CIN, satellite lesions may be present, and HPV lesions may be within or outside the transformation zone on the portio of the cervix. Another appearance of HPV may be snow-white, shiny, and raised lesions. Frequently, fine-caliber blood vessels are present. The appearance of HPV lesions are described by the Reid's colposcopic index, which assesses margin, color, vascular patterns, and iodine uptake.

  • Lesions suggestive of HPV should be confirmed by performing a biopsy. The hallmark histologic feature is the koilocyte. On both cytologic preparations of cervical biopsy specimens, koilocytes are cells with wrinkled nuclear membranes (like raisins) that are frequently binucleate and occasionally multinucleate. The nuclei are surrounded by a clear halo, which gives the cells their name. Cytologic and nuclear atypia is typically present. In cervical biopsy specimens, a few normal mitotic figures may be seen in the basal layer of the squamous epithelium, while koilocytes occupy the intermediate and superficial layers. ^[21]

  • The prevalence of high-risk HPV in abnormal vaginal smear findings parallels that of cervical smear findings, with equivalent degrees of abnormality. ^[22] Women with abnormal vaginal smear findings may benefit from reflex high-risk HPV testing.

  • The following three vaccines for the prevention of HPV-related cervical, vaginal, and vulvar cancer and warts were approved by the US Food and Drug Administration (FDA) ^{[23, 24]} :

    • Gardasil is a quadrivalent HPV recombinant vaccine containing activity against HPV types 6, 11, 16, and 18. ^[25] The vaccine is indicated for prevention of HPV-associated dysplasias and neoplasias, including cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical intraepithelial neoplasia grades 1, 2, and 3; vulvar intraepithelial neoplasia grades 2 and 3; vaginal intraepithelial neoplasia grades 2 and 3). The immunization series should be administered to girls and young women aged 9-26 years. It is administered as a series of 3 doses, typically at 0, 2, and 6 months; however, it is equally effective if all doses are given within 1 year. ^[12] In October 2009, the Gardasil vaccine received FDA approval for the prevention of genital warts in men and boys. ^[26]  The original Gardasil is no longer available for use in the United States.

    • Cervarix is the second HPV vaccine and is also a recombinant formulation. This vaccine is designed to create immunity against the L1 protein of HPV subtypes 16 and 18, which cause 70% of cervical cancer. It received FDA approval in September 2009. ^[27]  Cervarix is no longer available for use in the United States.

    • In 2014, the FDA approved Gardasil 9, a nonavalent HPV vaccine that contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It is indicated in females aged 9-45 years for the prevention of cervical, vulvar, vaginal, and anal cancer. Additionally, it is indicated to prevent genital warts and precancerous or dysplastic lesions caused by HPV. It is also indicated in males aged 9-45 years to prevent genital warts (condyloma acuminata) caused by HPV types 6 and 11; anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; and anal intraepithelial neoplasia caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. ^{[28, 29]}  

  • Most parents accept HPV vaccination of their daughters, but at this time they also want more information. ^[30]

  • The Advisory Committee on Immunization Practices (ACIP) recommends that the HPV vaccine be administered to girls at the age of 11 or 12 years. Although most women's healthcare practitioners do not care for patients that young, catch-up vaccinations are recommended for females aged 13-26 years. HPV vaccines are most effective if given prior to exposure to HPV, but sexually active females can benefit from vaccination. Healthcare providers are encouraged to discuss the benefits and limitations of the vaccine and the need for routine cervical cytology examinations in patients older than 21 years. ^[24]

  • Children and adolescents aged 15 years and younger need two, not three, doses of the Gardasil 9 vaccine; this ACIP recommendation stems from the vaccine’s enhanced immunogenicity in preteens and adolescents aged 9-14 years. The schedule for older adolescents and young adults aged 15-45 years is 2-3 inoculations (depending on immunization history) within 6 months. For adults aged 27-45 years, the need for vaccination is based on shared decision making between patient and clinician. ^[31]

• Herpes simplex virus (HSV)

  • Both serotypes of HSV (HSV-1 and HSV-2) can cause genital tract lesions. Of women with their first episode of HSV-2 infection, 70-90% have herpetic cervicitis as part of the manifestation. In recurrent infections, cervicitis is present in 15-20% of women.

  • Primary herpetic cervicitis frequently is asymptomatic; however, it may present as a purulent or bloody vaginal discharge. Grossly, the cervix may appear diffusely red and friable. At times, ulcerations, which may be extensive, are present on the ectocervix.

  • Making a clinical diagnosis may be difficult. Colposcopic findings of acute cervicitis are identifiable in two thirds of women with primary herpes cervicitis. Multinucleate cells with typical ground-glass inclusions may be identified on cervical cytology results in 60% of these women.

  • The differential diagnosis includes the chancre of syphilis. Gonorrhea and chlamydia infection can cause a similar type of discharge, although ulceration in these conditions is uncommon. Syphilis, gonorrhea, and chlamydia infection may coexist with HSV-2 infection. Women with primary genital herpes involving the cervix should be started on antiviral therapy.

  • Treatment with acyclovir, famciclovir, or valacyclovir is appropriate.

  • The other presentation of herpes involving the cervix is asymptomatic shedding. In these instances, the classic multinucleate cells with ground-glass inclusions may be identified on cervical cytology results as an incidental finding. In a sexually transmitted disease clinic, HSV was isolated from 4% of randomly selected women. Treatment for asymptomatic shedding in the non-pregnant patient is not recommended.

  • The American College of Obstetricians and Gynecologists (ACOG) released recommendations regarding the specific treatment and management of HSV infection in pregnancy. ^[32]

• Treponema pallidum

  • Treponema pallidum is a spirochete that causes syphilis. The primary lesion of syphilis develops at the site of inoculation 2-6 weeks after infection. The primary lesion begins as a papule and then ulcerates. Typically, the diameter is 0.5-1.5 cm. ^[33]

  • In women, besides the labia and posterior fourchette, the cervix is a common site for the primary chancre. Because the primary lesion is asymptomatic and the cervix is not visualized readily, primary lesions in this location frequently remain undiagnosed. If untreated, they heal in 3-6 weeks and the disease then enters the latent period. ^[34]

  • The differential diagnosis of these ulcers includes HSV-2 and Hemophilus ducreyi. Diagnosis is best made using a dark-field microscopic examination of exudate taken from the surface of the lesion. The rapid plasma reagin (RPR) test results may be positive at a relatively low titer (1:16 or less) at this time. If syphilis is strongly considered and both the dark-field examination and the RPR test findings are negative, a repeat RPR test in 2 weeks will have positive results.

  • Treatment for primary syphilis is benzathine penicillin G at 2.4 million units. If the patient is allergic to penicillin, doxycycline at 100 mg twice daily for 2 weeks by mouth or tetracycline at 500 mg 4 times/d by mouth for 2 weeks is acceptable. If the patient is pregnant, desensitization followed by treatment with penicillin is recommended.

  • All patients with a diagnosis of syphilis should be tested for HIV.

• Hemophilus ducreyi

  • The primary ulcer is a painless chancroid and is typically on the fourchette, labia, or vestibule.

  • Vaginal wall ulcers can occur and, at times, involve the cervix. Involvement of the cervix alone is very rare.

• Calymmatobacterium granulomatis

  • C granulomatis causes a sexually transmitted disease called granuloma inguinale. The typical site of infection in women is the labia minora and the fourchette. Lesions of the cervix are uncommon but are easily confused with cervical carcinoma.

  • Four distinct types of lesions are described; the most common lesion on the cervix is the necrotic, deep, foul-smelling ulcer associated with tissue destruction.

  • A tissue smear is the mainstay of diagnosis. A Giemsa stain typically is used. The Donovan bodies are identified in monocytes. The characteristic histologic picture is that of chronic inflammation, with plasma cells and polymorphonuclear leukocytes. Rarely, Donovan bodies are identified on cervical cytology.

  • Treatment is with trimethoprim-sulfamethoxazole double-strength tablets twice daily or doxycycline at 100 mg orally twice daily. Alternative regimens include ciprofloxacin at 750 mg twice daily or erythromycin base at 500 mg 4 times daily. Treatment is for a minimum of 3 weeks.

• Actinomyces organisms

  • Actinomyces organisms are isolated most commonly in women with intrauterine devices (IUDs), but infection can be a result of surgical instrumentation and abortion.

  • Demonstrating the organism in the center of large abscesses confirms the diagnosis.

  • Lesions appear yellow and granular to the naked eye, hence the term sulfur granule.

  • If this is an incidental finding, it does not need to be treated. Treatment with long course penicillin therapy is indicated only in the rare instances where an abscess is present.

• Tuberculosis

  • When the cervix is involved, the lesion almost always is secondary to tuberculous salpingitis, which is secondary to pulmonary tuberculosis.

  • The gross appearance can be confused with invasive carcinoma.

  • Histologically, multiple granulomas or tubercles with central caseation necrosis, epithelioid histiocytes, and multinucleated Langerhans giant cells characterize the lesions. ^[35]

  • The differential diagnosis includes lymphogranuloma venereum and sarcoidosis. An unequivocal diagnosis requires the identification of acid-fast Mycobacterium tuberculosis.

• Protozoal and parasitic cervicitis: These are usually part of a more generalized process.

• Schistosomiasis and amebiasis: These are common in certain geographic areas.

Atypia of Repair

This is a response to any injury that is characterized by epithelial disorganization and nuclear atypia. In reactive atypia, the nuclei are uniform in shape and size and the chromatin is aggregated in prominent nucleoli. Mitotic figures are normal and confined to the parabasal and basal cells. Maturation occurs in a normal manner. In the endocervix, reparative changes include nuclear enlargement, hyperchromasia, cytoplasmic eosinophilia, and loss of the mucin droplets. ^[36]

Hyperkeratosis and Parakeratosis

This usually involves the cervical portio and may appear as whitish plaques (ie, leukoplakia). When diffuse, the portio is covered by a thickened, white, wrinkled epithelial membrane. The thick keratin layer on the surface is referred to as hyperkeratosis. When pyknotic nuclei are found within the keratin layer, the term parakeratosis is used. Acanthosis (ie, elongation of the rete pegs) is usually present.

Noninfectious Cervicitis

This includes chemical irritation (eg, deodorants, douching), local trauma from foreign bodies (eg, tampons, pessaries, IUDs), surgical instrumentation, and therapeutic intervention. Clinically, the cervix is swollen, erythematous, and friable, and an associated purulent discharge may be present. The epithelium may be denuded and ulcerated. In chronic cervicitis, the cervix may be extremely friable and postcoital bleeding is a presenting complaint. Microscopically, lymphocytes, histiocytes, and plasma cells are present, with varying amounts of granulation tissue and stromal fibrosis. Lymphoid follicles with germinal centers are occasionally found beneath the epithelium. Chlamydia infection is isolated in some of these women.

Endocervical polyps

Endocervical polyps are the most common benign neoplasms of the cervix. They are focal hyperplastic protrusions of the endocervical folds, including the epithelium and substantia propria. They are most common in the fourth to sixth decades of life and usually are asymptomatic but may cause profuse leukorrhea or postcoital spotting ^[37] .

Grossly, they appear as typical polypoid structures protruding from the cervical os. At times, endometrial polyps protrude through the cervical os. They cannot be distinguished from endocervical polyps by gross appearance. Microscopically, a variety of histologic patterns are observed, including (1) typical endocervical mucosal, (2) inflammatory (granulation tissue), (3) fibrous, (4) vascular, (5) pseudodecidual, (6) mixed endocervical and endometrial, and (7) pseudosarcomatous.

Treatment is removal, which can usually be accomplished by twisting the polyp with ringed forceps if the pedicle is slender. Smaller polyps may be removed with punch biopsy forceps. Polyps with a thick stalk may require surgical removal.

Microglandular hyperplasia

Microglandular hyperplasia refers to a clinically polypoid growth measuring 1-2 cm. It occurs most often in women who are on oral contraceptive therapy or Depo-medroxyprogesterone acetate resulting from the influence of progesterone. It also occurs in pregnant or postpartum women. On thin layer cytology, it may be confused with atypical squamous cells, cannot exclude high-grade lesion. ^{[38, 39, 40]}

Microscopically, it consists of tightly packed glandular or tubular units, which vary in size, lined by a flattened-to-cuboidal epithelium with eosinophilic granular cytoplasm containing small quantities of mucin. Nuclei are uniform, and mitotic figures are rare. Squamous metaplasia and reserve cell hyperplasia are common. An atypical form of hyperplasia can be mistaken for clear cell carcinoma. Unlike clear cell carcinoma, it lacks stromal invasion, has scant mitotic activity, and lacks intracellular glycogen. ^[41]

Squamous papilloma

Squamous papilloma is a benign solid tumor typically located on the ectocervix. It arises most commonly as a result of inflammation or trauma.

Grossly, the tumors are usually small, measuring 2-5 mm in diameter. Microscopically, the surface epithelium may show acanthosis, parakeratosis, and hyperkeratosis. The stroma has increased vascularity and a chronic inflammatory infiltrate. Treatment is removal. The squamous papilloma resembles a typical condyloma acuminatum but lacks the koilocytes microscopically.

Smooth muscle tumors (leiomyomas)

These benign neoplasms may originate in the cervix and account for approximately 8% of all uterine smooth muscle tumors. They are similar to tumors in the fundus. When located in the cervix, they usually are small, ie, 5-10 mm in diameter.

Symptoms depend on size and location. Microscopically, leiomyomas resemble the typical smooth muscle tumor found in the uterine corpus. Treatment is required only for those patients who are symptomatic. The cervical leiomyoma is usually part of the spectrum of uterine smooth muscle tumors.

Mesonephric duct remnants

When present, mesonephric duct remnants are typically located at the 3-o'clock and the 9-o'clock positions, deep within the cervical stroma. They usually are incidental findings and are present in approximately 15-20% of serially sectioned cervices. As the name implies, mesonephric duct remnants are vestiges of the mesonephric or Wolffian duct. Usually, they are only a few millimeters in diameter and seldom are grossly visible.

Microscopically, they consist of a proliferation of small round tubules lined by epithelium that is cuboidal to low columnar. The tubules tend to cluster around a central duct. The cells lining the tubules contain no glycogen or mucin, but the center of the tubule may contain a pink material that contains glycogen or mucin. ^[42]

Endometriosis

When present in the cervix, endometriosis is usually an incidental finding. However, it may present as a mass or abnormal bleeding, particularly postcoital. Grossly, it may appear as a bluish-red or bluish-black lesion, typically 1-3 mm in diameter. Diagnosis is made by colposcopy and colposcopically directed biopsy but at times is difficult. ^[43] Microscopically, the implants are typical endometriosis, consisting of endometrial glands, endometrial stroma, and hemosiderin-laden macrophages. The implants usually gain access to the cervix during childbirth or previous surgery. Management is expectant in almost all instances. ^[44]

Papillary adenofibroma

This neoplasm is uncommon. Grossly, it appears as a polypoid structure. On ultrasound, cystic areas within the neoplasm may be identified. Microscopically, the neoplasm contains branching clefts and papillary excrescences lined by mucinous epithelium with foci of squamous metaplasia. A compact, cellular, fibrous tissue composed of spindle-shaped and stellate fibroblasts supports the epithelium. The stroma is devoid of smooth muscle, and mitoses are rare. Similar growths occur in the endometrium and the fallopian tubes. ^[45]

Heterologous tissue

Heterologous tissue includes cartilage, glia, and skin with appendages. This type of tumor rarely occurs in the cervix. While they may arise de novo, these tumors probably represent implants of fetal tissue from a previous aborted pregnancy. ^[46]

Hemangiomas

Hemangiomas in the cervix are rare and are similar to those found elsewhere in the body. If symptomatic, they cause pain or vaginal bleeding. ^[47] The differential diagnosis includes cervical malignancy. Treatment is surgical. ^[48]

The cervix is the least common site for ectopic pregnancy. The implantation may be within the cervical canal or present as an exophytic lesion on the cervix. Grossly, a bluish hue may be present. In rare instances, a gestational sac and live fetus can be identified on ultrasonography. The trophoblast invades the stroma of the cervix. Because the pregnancy is not in a confined space, life-threatening hemorrhage may occur.

Cervical pregnancy is uncommon and the best treatment is not known; however, medical management is preferred. In one series, 36 cases have been treated with 50 mg of methotrexate injected under ultrasonographic guidance. In pregnancies with cardiac activity, 2 mL potassium chloride (KCL) is injected. ^[49] Case reports exist of angiographic uterine artery embolization followed by immediate curettage for controlling heavy bleeding or for recurrent heavy bleeding. ^[50]