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CERVIX

 

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


 

Embryology

 At 8 weeks gestation fusion of the distal portions of the müllerian ducts gives rise to the uterine fundus, the cervix, and the upper vagina.

In a female fetus, the müllerian duct persists, while 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

 

 

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.

The anterior and posterior fornices delimit the portio (exocervix).

The cervical canal measures approximately 8 mm wide and contains longitudinal ridges.

The area between the endocervical and endometrial cavity is called the isthmus or lower uterine segment.

the cervix occupies 2/3 of the entire length of the uterus in the prepupertal age then after puberty it equal the length of the corpus

in parous women the cervix become one-third of the uterus

Lymphatic drainage  

·        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.


 

  Innervation of the cervix is from the Frankenhäuser 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.

Blood Supply 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.

 

 

 

 

 

 

 

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. The native portio epithelium is replaced every 4-5 days, is sensitive to estrogen and progesterone, and contains glycogen. In postmenopausal women, the squamous epithelium is atrophic with little or no glycogen and the cellular alterations 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 lines both 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.

 

 

                  Ectocervix                            Endocervix

 

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 now is 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 young females, the endocervical tissue tends to roll out from the cervical os; this is called cervical eversion and corresponds to the original squamocolumnar junction. In a normal transformation, one can find remnants of gland openings and nabothian cysts. On the other hand, in postmenopausal women, the squamocolumnar junction frequently is located within the cervical canal. In this position, it is not visualized through speculum examination. Understanding the transformation is of utmost importance because cervical cancer and its precursors typically begin within the transformation zone. (see colposcopy)

 

 

Hormonal effect on the Cervix

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.

After ovulation, 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. During pregnancy, during the postpartum state, and in women who are on progestin therapy, microglandular hyperplasia may occur.  

 Decidual changes within the cervical stroma can also occur during pregnancy and high-dose progestin therapy.

Congenital Anomalies of the Cervix

  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.

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.

  Septate cervix, the appearance is that of 1 cervix with 2 separate cervical openings. The septum may be partial. The gross appearance is 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. (see uterine anomalies)

Congenital absence of the cervix

Congenital absence of the cervix usually occurs as part of the syndrome of müllerian agenesis, also known as Mayer-Rokitansky-Küster-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.

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. These patients require excision of the uterine bud. Although vaginal patency has been surgically created in a few patients, pregnancy has not occurred in the absence of a cervix.

In utero exposure to diethylstilbestrol and other nonsteroidal estrogens

Changes associated with in utero exposure to DES and other nonsteroidal estrogens are encountered. The epidemiologic association of in utero exposure to DES with clear cell vaginal adenocarcinoma has been known since 1970. The use of DES, which initially was prescribed for thousands of women to prevent miscarriage, was discontinued at approximately that time. 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 cause hypoplastic cervix,

other findings unique to in utero DES exposureinclude: .

-          vaginal adenosis,  

-           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.

complications

Incompetent cervix with pregnancy wastage is a potential problem in females exposed to DES

 

 

Cervicitis

 

Inflammation of the uterine cervix

Causes of Infectious cervicitis:

-          endocervical infection (mucopurulent) is caused by  Neisseria gonorrhoeae and Chlamydia trachomatis

-          Infection of portio vaginalis is caused by Trichomonas vaginalis, human papilloma virus (HPV), herpes simplex virus (HSV), Treponema pallidum, Haemophilus ducreyi, and donovanosis. These can produce either exophytic or ulcerative lesions

 

Causes of non-infectious cervicitis include:

-          Trauma from foreign bodies (eg, tampons, pessaries, IUDs), surgical instrumentation, and therapeutic intervention

-          Radiation

-          Malignancy

-          chemical irritation (eg, deodorants, douching),

 

Frequency of Infectious cervicitis

The World Health Organization estimates that at least 250 million new cases of sexually transmitted diseases occur each year

Trichomoniasis is the most common with approximately 120 million cases a     year

Chlamydia is the next most common STD with approximately 50-70 million cases a year

HPV, HSV and gonorrhea each account for roughly 20-30 million cases a year

Risk Factors

-          Youth eg. <25 year

-          Single marital status

-          Urban resident

-          Low Socioeconomic status

Complications of Cervicitis

-          Pelvic Inflammatory disease

-          Infertility

-          Ectopic pregnancy

-          Cervical cancer

-          Spontaneous abortion

-          Premature rupture of membranes and preterm delivery

-          Perinatal and neonatal infections which could lead to mental retardation, blindness, low-birth weight, stillbirth, meningitis and death

-          The social stigma is strong and might expose women to verbal, emotional, or physical abuse from others particularly male partner.

 

Clinical Picture

History taking

-          history of sexual activity and type of contraception (if any). Increased incidence of Chlamydia cervicitis in women has been associated with use of oral contraception

-          Most patients present with complaints of vaginal discharge or vaginal bleeding

-          Dyspareunia and dysuria may be present

-          Abdominal pain and fever are associated with involvement of the upper genital infection

-          Patients with mild cervicitis may be asymptomatic, and many patients with chlamydial cervicitis are asymptomatic

 

Physical Examination

Finding in the cervix include the following:

-          Erythematous and inflamed cervix on speculum examination

-          Possible purulent discharge from the cervical os

-          Cervix tender to palpation

-          T Vaginalis may result in a friable cervix with prominent papillae and punctuate hemorrhage (strawberry cervix)

Investigations

Traditional tests

·        Wet mount of the discharge usually demonstrates more than 5 WBCs per high-power field

·        Gram stain of the cervical mucopus may reveal gram-negative intracellular diplococci in cases of gonorrhea. Culturing in modified Thayer-Martin medium is the criterion standard for confirming gonorrhea

·        Enzym-linked immunoassay or direct fluorescent antibody testing often is used to detect Chlamydia infection.  DNA probes with 90-97% sensitivity are also available for simultaneous detection of gonococcal and chlamydial organisms

·        Chlamydia culture is performed on McCoy cells sometimes indicated (in case of suspected child abuse)

 

Newer Tests

Several high specific and sensitive tests have been developed including:

·        Polymerase chain reaction (PCR)

·        Ligase chain reaction (LCR)

·        Transcription mediated amplification (TMA)

-          PCR and LCR testing consists of amplification of specific DNA sequences, while TMA testing is an RNa amplification assay

-          It is better to do these tests with endocervical specimens, but they may be easily performed on first-void morning urine samples

 

Management

-          Establishing the etiologic agent is the key to successful treatment

-          Ensure that patient's sexual contacts receive the appropriate examination and treatment . Most treatment failures are actually reinfection from an untreated sexual partner

-          Advise patients to abstain from sexual activity until test results following therapy are negative and partners are treated.

Drug therapy:

-Ceftriaxane (rocephin)  first choice for the treatment of gonorrhea …125mg IM single dose . Cass b in pregnancy and pediatric dose as adult

- Doxycycline is the treatment of choice for chlamydia.. 100mg orally(PO) bid for 7 days. Unsafe in pregnancy and contraindicated before 8 year-old

- Azithromycin (Zithromax) for chlamydia  …1g po single dose

Class b in pregnancy. 10mg/kg not to exceed 1g/dose In children

- Metronidazole (Flagyl) 2g po single dose for T vaginalis

(see also STD and vulvoaginitis)

Infections involving the portio of the cervix

 

Bengin Lesions of the cerfvix

 

Hyperkeratosis and Parakeratosis 

This usually involves the 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.

Diffuse leukoplakia seen by naked eye without acetic acid

 

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.

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, 

 (7) pseudosarcomatous.

Treatment is removal, which can usually be accomplished by twisting the polyp with a dressing 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-Provera and in pregnant or postpartum women and reflects the influence of progesterone.

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

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.

Endometriosis

When present in the cervix, endometriosis is usually an incidental finding. Grossly, it may appear as a bluish-red or bluish-black lesion, typically 1-3 mm in diameter. 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.

Papillary adenofibroma

This neoplasm is uncommon. Grossly, it appears as a polypoid structure. 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.

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.

Hemangiomas

Hemangiomas in the cervix are rare and are similar to those found elsewhere in the body.

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july 2009

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