The Female Genital Tract and Breasts

Chapter 17 The Female Genital Tract and Breasts

Ivan Damjanov, MD, PhD

INFECTIONS

3 How common are sexually transmitted diseases (STDs)?

They are very common. In the United States, there are approximately 5 million women infected with genital herpes simplex virus (HSV-2), 3 million infected with Chlamydia trachomatis, and 2 million genitally infected with human papillomavirus (HPV).

4 What are the main signs and symptoms of STDs?

Vaginal discharge

Vulvar lesions (e.g., vesicles and ulcers)

Pelvic pain or pelvic mass

Discomfort during intercourse (dyspareunia)

5 Name the main viral pathogens causing infections of the lower female genital tract (vulva, vagina, and cervix)

HSV-2: It causes vesicles, which coalesce and ulcerate. These vesicles appear 3 to 7 days after the infecting intercourse but in only approximately 30% of infected women. Ulcers may persist for 1 to 3 weeks but heal spontaneously without scarring. The virus migrates along the nerves to the lumbar ganglia, where it remains in a content form forever. The virus can be reactivated and descend to the vulva to produce recurrent vesicles.

HPV: The disease causes chronic infections, some of which heal spontaneously, whereas others ultimately lead to the formation of cancer. Giant vulvar wart is called condyloma acuminatum. HPV-related lesions of the vagina and the cervix are usually flat and are best recognized in Papanicolaou smear.

6 What are the most common causes of vaginitis?

Candida albicans: This fungus is found in the vagina of approximately 10% of women, who are usually unaware of the infection. Pregnancy, oral contraceptives, and diabetes promote fungal growth and cause the appearance of white patches on the mucosal surface and increased vaginal discharge with itching. Diagnosis is best made microscopically on wet mounts or Pap smear.

Trichomonas vaginalis: These flagellated protozoa are best diagnosed microscopically in freshly prepared wet mounts (i.e., smears of unfixed vaginal discharge, in which the protozoa keep moving). T. vaginalis is also visible on routine Pap smear.

Gardnerella vaginalis: This microbe grows in the vagina. The infection is best recognized on Pap smear by the appearance of “clue cells” (i.e., squamous cells covered with bacilli). Cytologic findings in various forms of vaginitis are illustrated in Fig. 17-1.

Figure 17-1 Cytologic findings in various forms of vaginitis. In all vaginal smears, one may see desquamated epithelial vaginal cells and inflammatory cells (neutrophils). A, Candida albicans vaginitis. The smear contains fungal hyphae. B, Trichomonas vaginalis. The smear contains ciliated protozoa. C, Gardnerella vaginalis. The smear contains “clue cells” (i.e., squamous cells with clumped nuclei, folded cytoplasm, and numerous bacteria attached to their surface).

7 What is pelvic inflammatory disease (PID)?

In clinical practice, the term PID is used for extensive infections involving more than one part of the upper female genital tract. Infections of the fallopian tubes (salpingitis), which are almost invariably present, may be accompanied by endometritis or oophoritis and peritonitis. Pus tends to accumulate in the fallopian tubes (pyosalpinx), but it may penetrate into the pelvis, where it accumulates in the pockets formed by fibrous adhesions with other pelvic organs (e.g., tuboovarian abscess).

8 Describe the most common causes of PID

PID is most often a complication of sexually transmitted infections caused by Neisseria gonorrhoeae and C. trachomatis. Less often, PID is a complication of puerperal infections (i.e., polymicrobial ascending infection during delivery or abortion). In such cases, PID is caused by staphylococci, streptococci, or enteric bacteria, which usually invade the upper genital tract jointly from the infected uterus.

VULVA AND VAGINA

10 What are the most common diseases of the vulva?

The vulva is most often involved by infections, especially those that flourish in moist areas (e.g., candidiasis) or involve hair follicles (e.g., staphylococcal boils). Skin of the vulva may be involved with any other skin disease, such as psoriasis or eczema. Vitiligo (i.e., loss of pigmentation of unknown etiology) also may involve vulva.

13 What is koilocytosis?

Koilocytosis is a sign of HPV infection. The nuclei of infected squamous cells show irregular contours and appear crenated or “raisin-like.” The nucleus is hyperchromatic, displaced laterally by clear cytoplasm. Hence the name, which in translation from Greek means “spoonlike cell.” The virus particles can be seen in the nucleus on electron microscopy and are also demonstrable by immunohistochemistry.

14 How common is carcinoma of the vulva?

Carcinoma of the vulva is rare. Usually diagnosed in elderly women, it accounts for only 3% of all cancers of the female genital tract and is 8 times less common than cervical cancer.

15 What is vulvar intraepithelial neoplasia (VIN)?

VIN, also known as vulvar carcinoma in situ or Bowen disease, is a preinvasive squamous cell carcinoma. It is often multicentric, and like cervical or vaginal carcinoma, it is usually associated with HPV infection.

16 Describe the histologic features of vulvar carcinoma

Most vulvar carcinomas are histologically classified as keratinizing or poorly differentiated (basaloid) squamous cell carcinomas. Other histologic forms, such as extramammary Paget disease or melanoma, are rare.

17 How common is carcinoma of the vagina?

Carcinoma of the vagina is rare, accounting for 1% of all female genital cancers.

18 Discuss the histologic features of vaginal carcinoma

Most vaginal carcinomas diagnosed in adult women are of the squamous cell type. Clear cell adenocarcinomas are rare vaginal tumors, most of which were found in young women whose mothers took diethyl stilbestrol during pregnancy. Sarcoma botryoides is a rare vaginal tumor of girls younger than 5 years.

CERVIX

19 What are the most common causes of cervicitis?

Cervicitis occurs in several forms. Mucopurulent acute cervicitis is typically a feature of sexually transmitted infections and is most often caused by Chlamydia and N. gonorrhoeae invading the endocervix. These infections may persist and spread upward to cause endometritis or PID. Chronic persistent or recurrent infection of the squamous epithelium of the exocervix is typically caused by viruses—HPV and HSV-2. Mild, nonspecific chronic inflammation of the endocervix caused by vaginal saprophytic bacteria is found in many women but is of no clinical significance. In some women, it may lead to the formation of endocervical polyps, which cause “spotting.”

20 How common is cervical carcinoma?

Invasive carcinoma of the cervix is the second most common malignant tumor of the female genital tract. Although only 13,000 new cases of invasive cervical carcinoma are diagnosed annually, approximately 1 million others are detected in the preinvasive stages by Pap smear and cured before they become invasive.

22 What is the most efficient way to diagnose cervical carcinoma?

Tumor cells can be easily scraped from the cervix during routine gynecologic examination; thus Pap smears are the most efficient means for diagnosing preinvasive and invasive cervical carcinoma. Positive exfoliative cytology findings need to be confirmed by a biopsy, which is usually performed under colposcopic guidance. A colposcope, which serves as an intravaginal microscope, provides the gynecologist with a close-up magnified view of the cervix and allows him or her to take the tissue specimens from the pathologically altered portion of the cervix.

23 Define cervical intraepithelial neoplasia (CIN)

CIN represents a spectrum of neoplastic changes of the squamous epithelium of the cervix that have been recognized as precursors of invasive squamous cell carcinoma. CIN is graded on a scale from I to III, which can also be expressed descriptively as mild, moderate, or severe dysplasia, or carcinoma in situ. On Pap smear, these lesions are classified by cytologists as squamous intraepithelial lesions of low or high grade.

CIN I is usually caused by low-risk types of HPV. Koilocytic atypia is typically limited to the lower third of the squamous epithelium. If the atypia becomes more pronounced and extends toward the surface layers of the squamous epithelium, it is classified as moderate (CIN II). If the nuclear atypia can be found in all layers of the epithelium, which in such cases shows no signs of surface maturation, the cancer is classified as CIN III. Lesions classified as CIN II and CIN III are caused by high-risk types of HPV.

24 Does CIN always progress to invasive carcinoma?

Most CINs do not progress to invasive cancer. However, in each case, it is not possible to predict whether the lesion will progress to invasive cancer or regress. Therefore all CINs are treated as potential cancers. The chances that CIN will progress to invasive cancer depend on its grade. More than 85% of all CIN I cancers regress spontaneously, 10% progress to CIN III, and 2% or 3% progress to invasive cancer. Approximately 25% of all untreated cases of CIN III will progress to invasive carcinoma, usually within 10 years of diagnosis.

25 How is CIN treated?

The treatment of CIN depends on its grade and the extent of cervical involvement. Following initial biopsy, CIN I is followed up with regular Pap smears, colposcopic examinations, or both at regular time intervals. High-grade CIN must be removed surgically by conization (i.e., removal of the involved cone of tissue around the endocervical canal and the transformation zone by laser vaporization or cryosurgery). Women diagnosed with CIN are at risk of developing cancer of the cervix or carcinoma of the vulva and vagina and should be examined at regular time intervals for life.

26 Describe the peak age incidence for CIN and invasive cervical carcinoma

The age of presentation of CIN I and CIN II peaks at 25 years. The incidence of CIN III reaches its peak between 35 and 40 years, and the peak for invasive cervical carcinoma is approximately 50 years. Assuming that a lesion arose as a CIN II at age 25 years, one can predict that an untreated lesion will progress to carcinoma in situ over 10 to 15 years and from carcinoma in situ to invasive cancer in the next 10 to 15 years.

27 Has the peak age incidence for CIN and invasive cancer decreased during the past two decades?

CIN is being diagnosed earlier. Epidemiologic data show that all forms of cervical neoplasia are being diagnosed in younger women compared with a few decades ago. In part, this is because sexual mores have changed and many women become sexually active at an earlier age. It is also related to the widespread use of Pap smears in most developed countries. However, this does not explain the increased incidence of invasive cervical cancer in women younger than 35 years, which has been recorded worldwide.

29 What are the histopathologic features of invasive cervical carcinoma?

Approximately 85% of all cervical carcinomas are classified as squamous cell carcinomas. Adenocarcinomas originating from the endocervical glands account for approximately 10% of tumors. The remaining 5% of cancers comprise the less common variants, such as adenosquamous, neuroendocrine (oat cell), and undifferentiated carcinomas.

30 How does cervical carcinoma spread?

Cervical carcinoma tends to invade the vagina and parametria locally and also metastasize to the pelvic lymph nodes. Invasion of the rectum, urinary bladder, and distant metastases are found in later stages of cancer spread. Obstruction of the urinary outflow is a common cause of death.

BODY OF THE UTERUS

32 Name the most important diseases of the body of the uterus

Hormonal disorders with dysfunctional endometrial bleeding or endometrial hyperplasia

33 What are the causes of dysfunctional uterine bleeding?

Dysfunctional uterine bleeding is defined as bleeding that does not have an organic cause and is presumptively related to some endocrine disturbance. The main causes are:

Failure of ovulation: The normal menstrual cycle consists of a proliferative and a nonproliferative stage, separated by the midcyclic point of ovulation. At ovulation, the endometrium ceases to proliferate and enters a nonproliferative secretory phase. If ovulation does not occur, the endometrium will continue to proliferate until it outgrows its own blood supply. At that point, the surface portion of the endometrium becomes ischemic and starts dying off. This leads to bleeding, which typically occurs 2 or 3 weeks after the date of the “missed menstruation.” Anovulatory bleeding occurs most often around puberty and menopause but may be caused by neuroendocrine disturbances (e.g., anxiety and anorexia nervosa), severe malnutrition, or debilitating diseases.

Luteal phase inadequacy: If the corpus luteum does not secrete progesterone in adequate amounts, the level of progesterone may not be sufficient to transform fully the proliferative endometrium into a secretory endometrium. Such irregular maturation of the endometrium is usually associated with “spotting,” premature onset of menstrual bleeding, or prolonged bleeding. Curetting of endometrium performed to determine the cause of bleeding often may also help reestablish the normal cycle. In many cases, irregular bleeding recurs; such women may have problems conceiving.

34 What is endometrial hyperplasia?

Endometrial hyperplasia, or excessive proliferation of endometrium, is thought to be caused by estrogenic stimulation, even though in most cases the cause of hyperestrinism cannot be identified. Identifiable causes include:

Anovulatory hyperplasia in which estrogenic effect are not opposed by progesterone

Exogenous estrogen in women on hormone replacement therapy

Estrogen-producing ovarian tumors (e.g., theca or granulosa cell tumor)

Polycystic ovary syndrome

35 Discuss how endometrial hyperplasia is diagnosed

Endometrial hyperplasia is diagnosed microscopically by the pathologist examining the tissue removed by endometrial biopsy or endometrial curettage. Histologically, there are three forms of endometrial hyperplasia, as shown in Fig. 17-2:

Simple hyperplasia: The endometrium contains an increased number of dilatated glands.

Complex hyperplasia without atypia: The glands appear crowded and are surrounded by relatively scant stroma. The glandular epithelium are lined by uniform cells, which show no nuclear atypia.

Complex hyperplasia with atypia: The glands appear crowded and have an irregular shape, with stratification of cells that often protrude into the lumen. Nuclei of these glands show atypia, and sometimes it is not possible to distinguish them from well-differentiated adenocarcinoma. Some pathologists call it endometrial intraepithelial neoplasia.

Figure 17-2 Endometrial hyperplasia. A, Simple hyperplasia. The endometrium contains an increased number of dilatated glands separated from each other by normal stroma (“Swiss-cheese pattern”). B, Complex hyperplasia without atypia. The endometrium contains an increased number of irregularly shaped glands surrounded by scant stroma. Glandular atypica is not accompanied by cytologic atypia. C, Complex hyperplasia with atypia. There is both histologic and cytologic atypia; the glands are irregular, and the cells forming the glands are hyperchromatic and vary in size and shape.

36 What is the significance of endometrial hyperplasia?

Simple hyperplasia is a relatively innocuous lesion. Complex hyperplasia, however, can progress to cancer. Only 5% of complex hyperplasias without atypia ultimately progress to cancer. The rate of progression is much higher for complex hyperplasias with atypia; approximately 25% of all patients with these lesions will develop endometrial carcinoma.

37 What are endometrial polyps?

Endometrial polyps are solitary fingerlike lesions found in the uterine cavity. Polyps are most likely benign tumors, but some authorities believe that they are nonneoplastic. They are covered by columnar epithelium similar to that covering the surface of the endometrium. Inside the polyp are cystic endometrial glands embedded in rather cellular and fibrotic stroma. Most polyps are diagnosed in perimenopausal women complaining of spotting or irregular bleeding. Polyps are easily removed by curettage.

38 Name the most common tumors of the uterus

The most common uterine tumor encountered in clinical practice is leiomyoma. The most common malignant tumor is adenocarcinoma of the endometrium.

39 Are all endometrial tumors malignant?

Endometrial adenocarcinoma does not have a benign equivalent; if it did exist, it would be called endometrial adenoma. Hence, for practical purposes, all endometrial neoplasms should be considered malignant.

40 How common are endometrial adenocarcinomas?

Endometrial adenocarcinoma is the most common invasive cancer of the female genital tract. There are approximately 35,000 new cases of endometrial cancer diagnosed annually in the United States. However, most of these cases are diagnosed in early stages when the cancer is curable; thus only 6000 women die every year of this cancer.

41 Discuss the causes of endometrial cancer

Like endometrial hyperplasia, endometrial cancer is thought to be related to hyperestrinism. Endometrial hyperplasia is a common precursor and is the most important warning sign that an invasive carcinoma may develop. Other conditions associated with hyperestrinism, such as estrogen-producing ovarian lesions, are also associated with an increased incidence of endometrial cancer. Exogenous estrogens, especially if unopposed by progesterone, increase the risk of endometrial cancer 3 or 4 times.

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Tags: Pathology Secrets

Jul 23, 2016 | Posted by admin in PATHOLOGY & LABORATORY MEDICINE | Comments Off

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