|
|
|
Cervical polyps are usually derived from the endocervix as a result of a chronic papillary endocervicitis and present as soft, spherical, glistening red masses several millimeters to several centimeters in size (Fig. 6-10) . They are frequently quite friable and may be associated with profuse leukorrhea secondary to the underlying endocervicitis. Histologically they are composed of endocervical epithelium with a fibrovascular stalk. The differential diagnosis includes (1) polypoid fragments of endocervical carcinoma or carcinosarcoma protruding through the os; (2) retained products of conception; (3) the grape-like swellings of sarcoma botryoides that occasionally originate in the cervix; and (4) prolapsing submucous fibroids or endometrial polyps. Most cervical polyps can be grasped with a clamp and twisted free, and the base cauterized for hemostasis. Certainly all cervical polyps should be submitted for pathologic evaluation, although malignancy is extremely rare.
Leiomyomas or fibroids are the most common uterine tumors. Cervical involvement occurs in as many as 8% of cases. Cervical leiomyomas are grossly and histologically identical to those found in the corpus. Although they are frequently incidental findings on physical examination, with excessive
Endometriosis of the cervix presents as red or reddishblue vesicular lesions evident on the exocervix. They are usually asymptomatic but may cause dysmenorrhea or dyspareunia, which is most evident premenstrually. Biopsy specimens are best taken at this time for adequate pathologic interpretation. This pattern of endometriosis is frequently seen several months after cervical biopsy, cauterization, or trachelorrhaphy in menstruating women and thus suggests implantation as its etiology. However, areas of decidual reaction may occasionally be seen in the cervices of pregnant women who have not undergone any cervical procedures. This suggests that multi-potential cells capable of responding to estrogen and progesterone are present in the cervical stroma.
Infertility is associated with extensive cervical endometriosis and is probably due to destruction of endocervical glands and decreased mucous production. After biopsy confirmation, the treatment should consist of hormonal therapy and potentially deep cauterization, excision, or laser vaporization. Other less common benign tumors that may involve the cervix include hemangiomas, adenomyomas, fibroadenomas, fibromas, and lipomas.
Since keratinization is not a physiologic property of cervical squamous epithelium, any tendency in this direction must be considered abnormal, although some degree of focal keratinization may occasionally be observed in the absence of other abnormalities. Hyperkeratosis and parakeratosis usually appear grossly visible as white, raised plaques (leukoplakia) on the portio. Microscopically, hyperkeratosis exhibits a thickened layer of keratin, scant intraepithelial glycogen, and no cytologic atypia. It is not commonly seen except in cases of procidentia. Parakeratosis, the most common abnormality presenting as a white cervical lesion, exhibits similar features but with the retention of pyknotic nuclei in the keratin layer (Fig. 6-11) (Not Available). There is no evidence to indicate that either hyperkeratosis or parakeratosis is premalignant; however, these histologic features may be associated with cervical neoplasia. Therefore all white lesions of the cervix deserve biopsy for tissue diagnosis.
Figure 6-11 (Figure Not Available) A, Hyperkeratosis (x 120): normal ascending cellular
maturation with a thickened keratin layer can be seen. B, Parakeratosis (x 200): pyknotic nuclei are evident within the
keratin layer. (x 200.) (Courtesy Dr. Robert Ehrmann and the Division
of Women s and Perinatal Pathology, Brigham and Women s Hospital, Boston.)
From the time of the earliest clinical and microscopic descriptions of cervical disease, cervicitis has been implicated in the pathogenesis of cervical eversion, squamous metaplasia, basal cell hyperplasia, leukoplakia, polyps, and carcinoma. In the past a distinction was made between acute and chronic cervicitis. Although clinically difficult to distinguish, histology can be used to discern between the two entities. In chronic cervicitis, a neutrophilic infiltration with epithelial necrosis is found; whereas in acute cervicitis, stromal edema with a polymorphonuclear infiltrate and mucosal ulceration is seen. (101) (114)
Clinically the presenting symptoms are a purulent discharge and postcoital or postdouche vaginal spotting or bleeding. On physical examination, a reddened, often friable cervix covered with thick, tenacious, yellowish-white discharge is found. The inflammation or infection can be confined to the cervix or extend to the paracervical tissues, which gives the picture of pelvic inflammatory disease. A culture of the cervix can be done and the most common result is Chlamydia trachomatis. Other organisms can be cultured and in descending order of frequency after Chlamydia include the following: Neisseria gonorrhoeae, Trichomonas vaginalis, Candida, group B Streptococcus, Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum. Not all cases will be culture positive and an association between mucopurulent cervicitis and bacterial vaginosis, the use of oral contraceptives, and sexual contact with men who have nongonococcal urethritis increase the chance of similar symptoms occurring. (132)
A tentative diagnosis can be made on inspection; biopsy and tissue diagnosis are mandatory, however, to rule out a cervical neoplasia that can present with a similar clinical picture. The inflammation and bleeding associated with chronic cervicitis render Papanicolaou (Pap) smears unreliable in excluding carcinoma. Conversely those patients whose Pap smears reveal inflammation have the same chance of having a positive cervical culture as do patients whose smears do not reveal inflammation. Therefore Pap smears with inflammatory changes do not necessarily represent cervicitis. (88)
Once carcinoma is excluded, treatment can be offered. Those patients with a culture-proven organism can be treated by using the appropriate antibiotics. Patients for whom the culture is not positive can receive an empiric treatment course of antibiotics. If their cervicitis does not respond, other treatment methods that denude the epithelium can be used such as cryosurgery or laser. (107) Due to the excessive vaginal discharge that accompanies this problem, patients often prefer empiric treatment.
The role of C. trachomatis in the pathogenesis of genital tract disease has become well established. As many as 66% of women seen at venereal disease clinics may harbor Chlamydia in their cervices. Infection may be asymptomatic and limited to the cervix, or may ascend and cause pelvic inflammatory disease. A diagnosis requires culture techniques or the presence of the characteristic intracytoplasmic inclusion bodies as seen on Giemsa stains of cervical smears. Although several authors have reported an increased rate of cervical neoplasia in cervices harboring Chlamydia, (73) (85) a more recent study that controlled for the presence of human papillomavirus infection did not reveal any significant increase in preinvasive disease. (56) In fact low-grade, squamous intraepithelial lesions and atypia are not uncommon in the face of a chlamydial infection, and treatment must be completed before repeating the cervical smear. (77)
Figure 6-12 (Figure Not Available) Papanicolaou smear demonstrating T. vaginalis.
(x 800.) The characteristic pear-shaped protozoans with eccentrically placed,
spindle-shaped nuclei are shown (arrows).
The flagella are usually not well demonstrated on Papanicolaou smears. (Courtesy Dr. Robert Ehrmann and the Division of Women s and Perinatal Pathology,
Brigham and Women s Hospital, Boston.)
Trichomonas vaginalis is a flagellated protozoan that attacks the squamous epithelium of the vagina and cervix and destroys the epithelial cells on contact. In response there is an outpouring of polymorphonuclear leukocytes and a marked proliferation of small blood vessels that yield the characteristic colposcopic appearance of looped or hairpin capillaries. Although this infection may be asymptomatic, the classic presentation is a profuse, greenish-gray, frothy, vaginal discharge with pruritus, dysuria, and occasionally vaginal bleeding. Diagnosis is easily made from the presence of the
Tuberculous cervicitis is seen in approximately 3% to 5% of all cases of genital tuberculosis. The affected cervix may appear entirely normal, exhibit erythema with a mucopurulent discharge, or be invaded by a fungating mass suggestive of carcinoma. Histologically, caseating or noncaseating granulomas may be seen. Diagnosis requires the demonstration of acid-fast bacilli by suitable staining techniques or by culture. The differential diagnosis of granulomatous cervicitis includes syphilis, lymphogranuloma venereum, granuloma inguinale, chancroid, sarcoid, schistosomiasis, and pinworm.
Herpesvirus hominis types 1 and 2, the etiologic agents of genital herpes, belong to the group of herpes viruses that are found in almost every animal species studied. These are large DNA viruses with five members associated with disease in humans: herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus. Infection requires direct contact followed by an incubation period of 1 to 45 days and averaging 6 days. Clinically, herpes genitalis may be conveniently divided into either primary or recurrent infection, the former reserved for infection resulting from the first exposure to either HSV type 1 or 2 and the latter for any subsequent infection.
Multiple painful vesicles, usually 1 to 2 mm, appear on an erythematous background; these rapidly erode and coalesce to form larger ulcers. Cervical involvement occurs in 80% of primary infections and presents as a nonspecific inflammation, vesicles, ulcers, or occasionally as a fungating mass indistinguishable from invasive carcinoma. Symptoms include vulvar and pelvic pain, dysuria, and vaginal discharge, the last especially with cervical involvement. Complete healing requires several weeks as the symptoms and lesions slowly resolve. Recurrent pelvic infections involve the cervix less commonly than in primary infections. The clinical impression may be confirmed by tissue culture. Serologic conversion will occur after the initial infection. Therefore serology after an initial infection will not help confirm subsequent cervical infections. Cervical cytology, which is less sensitive than tissue culture, may demonstrate multinucleated giant cells or intranuclear viral inclusion bodies (Fig. 6-13) (Not Available).
Figure 6-13 (Figure Not Available) Pap smear exhibiting the characteristic features of herpesvirus infection.
(x 530.) Intranuclear inclusions (small arrows)
that may represent virus particles and multinucleated giant cells are evident.
Enlarged, ground-glass-appearing nuclei can also be seen (large arrow). (Courtesy Dr. Robert Ehrmann and the Division
of Women s and Perinatal Pathology, Brigham and Women s Hospital, Boston.)
Although human papillomavirus (HPV) does not cause a mucopurulent cervicitis, it is the most common cervical viral infection. The clinical manifestations of HPV infection can be divided into two types: the classic exophytic wart, or the changes that are associated with cervical neoplasia. The classic infection, described since the Roman-Hellenistic era, consists of an exophytic, grape-like lesion that is visible to the naked eye and is rarely found on the cervix (Fig. 6-14) (Not Available). Only 254 cases of cervical warts were reported in the literature through 1974. (119) In contrast, cervical neoplasia is considered to be epidemic with up to 600,000 cases identified yearly in the United States. (36)
The papovaviridae family is composed of two branches: simian virus 40 and polyomavirus make up one side and the papilloma viruses the other. HPVs are 8000-kilobase DNA viruses composed of many different subtypes. Each subtype represents a virus that has less than 50% DNA base sequence homology with other types. Currently there are more than 60 types of HPVs and each type appears to have a preference for a certain epithelial surface. For example, HPV type 1 is involved in plantar warts, whereas HPV types 5 and 14 are involved in a rare external skin disease, epidermodysplasia verruciformis. HPV types 6, 11, 16, 18, 31, 35, and some types in the 50s are found in genital epithelial surfaces.
Our understanding of HPV infections is greatly hampered by the lack of a culture system for the virus. For reasons yet unknown, the mature viral particle for HPV requires the permissive environment of a mature keratinocyte to form and replicate. This has required investigators to use various detection techniques, such as producing antibodies against the viral capsule proteins. The antibodies are then detected by immunoperoxidase staining. Other detection methods include characteristic histologic changes, and sophisticated DNA hybridization.
Microscopically the classic wart is characterized by papillomatosis, acanthosis, lengthening and thickening of the rete pegs, submucosal capillary proliferation, and the presence of koilocytes. Koilocytes, first described by Koss and Durfee in 1956, exhibit hyperchromasia, multinucleation, and perinuclear cytoplasmic vacuolization (Fig. 6-15) (Not Available). (67) Initially, koilocytes were believed to be pathognomonic of HPV infections, but as understanding of HPV expanded via DNA hybridization, this constant association was called into doubt. Further, long-term epidemiologic studies with extensive follow-up will be necessary before we can define more clearly the cytologic finding of koilocytosis.
In 1977 Meisels et al described two cervical lesions with koilocytotic atypia and other features suggestive of condylomata but without the typical gross papillary features. (79) The "flat condyloma" is a flattened area of acanthosis with mild accentuation of the rete pegs and koilocytotic changes. They pointed out the striking contrast between the essentially normal-appearing, deeper layers of the epithelium and the superficial areas that exhibit the koilocytosis. The second lesion they described is the endophytic or inverted condyloma that demonstrates gland involvement and may be mistaken for invasive carcinoma. Usually not visible without the colposcope, these lesions exhibit fine punctuation on a white background.
Meisels et al reviewed 152 cervical smears diagnosed as mild dysplasia and found that 70% were suggestive of HPV infection. (79) This finding led the authors to consider koilocytotic atypia as an early phase in the natural history of cervical neoplasia. The relationship between condylomata and cervical carcinoma will be more fully discussed later. Condylomatous cervicitis is a very common disease with 1% to 3% of all Pap smears exhibiting koilocytotic changes. When DNA hybridization techniques are used on Pap smears, the incidence of HPV is tenfold higher and represents 10% to 20% of all smears. (9) (72) If the polymerase chain reaction (PCR) is used as the basis of detection, the incidence of HPV infection varies from 2% to 80%. The variance is typically ascribed to differences in laboratory technique and in the population evaluated. (120) (124) (125)
The treatment of cervical condylomata depends on several factors, the most important of which are histology and
Figure 6-14 (Figure Not Available) Condyloma acuminatum of cervix. (From Kistner RW, Hertig AT: Obstet Gynecol 6:147, 1955.)
Figure 6-15 (Figure Not Available) A, Koilocytes on a Papanicolaou smear. (x 320.) The nuclei
are hyperchromatic with characteristic, perinuclear, cytoplasmic vacuolization.
Multinucleated forms are evident. A normal, superficial cell is shown for
comparison (arrow). B, Flat condyloma. (x 530.) Koilocytotic changes can be seen in the
superficial layers. (Courtesy Dr. Robert Ehrmann and the Division
of Women s and Perinatal Pathology, Brigham and Women s Hospital, Boston.)
|
|
|
"