Bartholin Cyst
Acute infection of the Bartholin gland produces an acute inflammation of the gland (adenitis) and may result in a Bartholin abscess. Bartholin cysts are relatively common, occur at all ages, and result from obstruction of the Bartholin duct, usually by a preceding infection. These cysts may become large, up to 3 to 5 cm in diameter. The cyst is lined by either the transitional epithelium of the normal duct or squamous metaplasia. The cysts produce pain and local discomfort; the cysts are either excised or opened permanently (marsupialization).
Pathology of The Cervix
Inflammations
ACUTE AND CHRONIC CERVICITIS
Morphology.
ENDOCERVICAL POLYPS
Intraepithelial and Invasive Squamous Neoplasia
Pathogenesis.
CERVICAL INTRAEPITHELIAL NEOPLASIA
Morphology.
SQUAMOUS CELL CARCINOMA
Morphology.
Clinical Course and Management.
Inflammations
ACUTE AND CHRONIC CERVICITIS
At the onset of menarche, the production of estrogens by the ovary stimulates maturation (glycogen uptake) of cervical and vaginal squamous mucosa. As these cells are shed, the glycogen provides a substrate for endogenous vaginal aerobes and anaerobes, streptococci, enterococci, Escherichia coli, and staphylococci. The bacterial growth produces a drop in vaginal pH. The exposed endocervix is sensitive to these changes in chemical environment and bacterial flora and responds by undergoing a variety of changes including proliferation of reserve cells leading to squamous metaplasia. This process of transformation from a columnar to a squamous lining is also hastened by trauma and other infections occurring in the reproductive years. As the squamous epithelium overgrows and obliterates the surface columnar papillae, it covers and obstructs crypt openings, with the accumulation of mucus in deeper crypts (glands) to form mucous (nabothian) cysts. This process is invariably associated with an inflammatory infiltrate composed of a mixture of polymorphonuclear leukocytes and mononuclear cells, and if the inflammation is severe, it may be associated with loss of the epithelial lining (erosion or ulceration) and epithelial repair (reparative atypia or anaplasia of repair). All of these components characterize what is known as chronic cervicitis.
Morphology
The pathologic correlates of acute and chronic cervicitis include epithelial spongiosis (intercellular edema), submucosal edema, and a combination of epithelial and stromal changes. Acute cervicitis is characterized by acute inflammatory cells, erosion, and reactive or reparative epithelial change. Chronic cervicitis includes inflammation, usually mononuclear, with lymphocytes, macrophages, and plasma cells. Necrosis and granulation tissue may also be present. Although the inflammation alone is not specific, some patterns are associated with certain organisms. HSV is most strongly associated with epithelial ulcers (often with intranuclear inclusions in epithelial cells) and a lymphocytic infiltrate, and C. trachomatis with lymphoid germinal centers and a prominent plasmacytic infiltrate. Epithelial spongiosis is associated with T. vaginalis infection.
ENDOCERVICAL POLYPS
Endocervical polyps are relatively innocuous, inflammatory tumors that occur in 2% to 5% of adult women. Perhaps the major significance of polyps lies in their production of irregular vaginal "spotting" or bleeding that arouses suspicion of some more ominous lesion. Most polyps arise within the endocervical canal and vary from small and sessile to large, 5-cm masses that may protrude through the cervical os. All are soft, almost mucoid, and are composed of a loose fibromyxomatous stroma harboring dilated, mucus-secreting endocervical glands, often accompanied by inflammation and squamous metaplasia. In almost all instances, simple curettage or surgical excision effects a cure.
Intraepithelial and Invasive Squamous Neoplasia
No form of cancer better documents the remarkable effects of prevention, early diagnosis, and curative therapy on the mortality rate than does cancer of the cervix. Fifty years ago, carcinoma of the cervix was the leading cause of cancer deaths in women in the United States, but the death rate has declined by two-thirds to its present rank as the eighth leading cause of cancer mortality. Cancer of the cervix causes about 4500 deaths annually (behind cancers of the lung, breast, colon, pancreas, ovary, lymph nodes, and blood.
Pathogenesis.
To understand the pathogenesis of cervical cancer, it is important to know the factors involved in its development, which have been identified from a series of clinical, epidemiologic, pathologic, and molecular studies. Epidemiologic data have long implicated a sexually transmitted agent, which is now established to be the human papillomavirus. HPV is currently considered to be the most important agent in cervical oncogenesis. As noted earlier, this virus is the known cause of the sexually transmitted vulvar condyloma acuminatum and has been isolated from vulvar and vaginal squamous cell carcinomas; it is also suspected of being an oncogenic agent in a variety of other squamous tumors or proliferative lesions of skin and mucous membranes.
Risk factors for cervical neoplasia:
• Early age at first intercourse
• Multiple sexual partners
• Increased parity
• A male partner with multiple previous sexual partners
• The presence of a cancer-associated HPV
• The persistent detection of a high-risk HPV, particularly in high concentration (viral load)
• Certain HLA and viral subtypes
• Exposure to oral contraceptives and nicotine
• Genital infections (chlamydia)
The molecular evidence linking HPV to cancer in general and cervical cancer in particular.
HPV DNA is detected by hybridization techniques in over 95% of cervical cancers.
Specific HPV types are associated with cervical cancer (high risk) versus condylomata (low risk); low (include types 6, 11, 42, 44, 53, 54, 62, and 66) and high-risk types (include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68).
Experimental data indicate that viral (E6 and E7) genes of high risk HPVs can disrupt the cell cycle via binding to RB with up-regulation of Cyclin E (E7) and p16INK4; interrupt cell death pathways by binding to p53 (E6); induce centrosome duplication and genomic instability (E6, E7); and prevent replicative senescence by up-regulation of telomerase (E6)
Morphology:
Range from lesions that are often indistinguishable histologically from condylomata acuminata and may be either raised (acuminatum) or macular (flat condyloma) in appearance.
These lesions typically exhibit nuclear enlargement and hyperchromasia in the superficial epithelial cells, signifying the effects of active viral replication in the maturing cells (viral cytopathic effect). The nuclear changes may be accompanied by cytoplasmic halos (koilocytotic atypia) with few alterations in the lower epithelial cells. Such changes fall within the range of CIN I. CIN I often contains abundant papillomavirus nucleic acids.
Raised lesions (acuminatum) often contain low-risk HPVs.
Flat CIN usually contain high-risk HPVs. However, they have a low rate of progression to cancer, underscoring the fact that the sequence of molecular events required for lesion progression often does not transpire or is interrupted by the host immune system.
The next change in the spectrum consists of the appearance of atypical cells in the lower layers of the squamous epithelium but nonetheless with persistent (but abnormal) differentiation toward the prickle and keratinizing cell layers. The atypical cells show changes in nucleo-cytoplasmic ratio; variation in nuclear size; loss of polarity; increased mitotic figThe next change in the spectrum consists of the appearance of atypical cells in the lower layers of the squamous epithelium but nonetheless with persistent (but abnormal) differentiation toward the prickle and keratinizing cell layers. The atypical cells show changes in nucleo-cytoplasmic ratio; variation in nuclear size; loss of polarity; increased mitotic figThe next change in the spectrum consists of the appearance of atypical cells in the lower layers of the squamous epithelium but nonetheless with persistent (but abnormal) differentiation toward the prickle and keratinizing cell layers. The atypical cells show changes in nucleo-cytoplasmic ratio; variation in nuclear size; loss of polarity; increased mitotic figures, including abnormal mitoses; and hyperchromasia—in other words, they take on some of the characteristics of malignant cells. These lesions fall within the range of CIN II.
Cervical cancer is staged as follows:
Stage 0. Carcinoma in situ (CIN III)
Stage I. Carcinoma confined to the cervix
Ia. Preclinical carcinoma, that is, diagnosed only by microscopy
Ia1. Stromal invasion no greater than 3 mm and no wider than 7 mm (so-called microinvasive carcinoma).
Ia2. Maximum depth of invasion of stroma greater than 3 mm and no greater than 5 mm taken from base of epithelium, either surface or glandular, from which it originates; horizontal invasion not more than 7 mm
Ib. Histologically invasive carcinoma confined to the cervix and greater than stage Ia2
Stage II. Carcinoma extends beyond the cervix but not onto the pelvic wall. Carcinoma involves the vagina but not the lower third.
Stage III. Carcinoma has extended onto pelvic wall. On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower third of the vagina.
Stage IV. Carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. This stage obviously includes those with metastatic dissemination.