Figure 22-16 In the diagram (upper), reserve cells in the transformation zone are continuous with the basal cells of the ectocervix (right) and may undergo columnar and squamous

differentiation (metaplasia). Photomicrographs at bottom depict (from left to right) quiescent subcolumnar reserve cells, reserve cells undergoing columnar differentiation (second from

left), reserve cells undergoing squamous metaplasia (second from right) and ectocervical squamous epithelium (right).

Figure 22-17Endocervical polyp composed of a dense fibrous stroma covered with endocervical columnar epithelium.

Figure 22-18 A, Postulated steps in the pathogenesis of cervical neoplasia. Conditions influencing progression are listed at the lower center of the diagram. B, Approximate lifetime risks of

acquiring HPV infection (left) and dying of cervical cancer (right). The intermediate steps include risks of infection with high-risk HPV types, development of advanced cervical

intraepithelial neoplasia (CIN), and progression to invasive carcinoma.

Figure 22-19Spectrum of cervical intraepithelial neoplasia: normal squamous epithelium for comparison; CIN I with koilocytotic atypia; CIN II with progressive atypia in all layers of the

epithelium; CIN III (carcinoma in situ) with diffuse atypia and loss of maturation.

Figure 22-20 A, Histology of CIN I (flat condyloma), illustrating the prominent koilocytotic atypia in the upper epithelial cells, as evidenced by the prominent perinuclear halos. B, Nucleic

acid in situ hybridization of the same lesion for HPV nucleic acids. The blue staining denotes HPV DNA, which is typically most abundant in the koilocytes. C, Diffuse immunostaining of

CIN II for Ki-67, illustrating widespread deregulation of cell cycle controls. D, Up-regulation of p161NK4 (seen as intense immunostaining) characterizes high-risk HPV infections.

Figure 22-21The cytology of cervical intraepithelial neoplasia as seen on the Papanicolaou smear. Cytoplasmic staining in superficial cells (A&B) may be either red or blue. A, Normal

exfoliated superficial squamous epithelial cells. B, CIN I. C, CIN II. D, CIN III. Note the reduction in cytoplasm and the increase in the nucleus to cytoplasm ratio, which occurs as the

grade of the lesion increases. This reflects the progressive loss of cellular differentiation on the surface of the lesions from which these cells are exfoliated (see Figure 22-19 ). (Courtesy of

Dr. Edmund S. Cibas, Brigham and Women's Hospital, Boston, MA.)

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) ( Fig. 22-22B ).

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.

Ten per cent to 25% of cervical carcinomas are adenocarcinomas, adenosquamous carcinomas,

Figure 22-22The spectrum of invasive cervical cancer. A, Carcinoma of the cervix, well advanced. B, Early stromal invasion occurring in a cervical intraepithelial neoplasm.

Figure 22-23Morphology of cervical cancers. A, Squamous carcinoma. B, Adenocarcinoma in situ (lower), associated with CIN 3 (upper). C, Adenocarcinoma. D, Neuroendocrine

carcinoma.

Figure 22-24Electron micrograph of virus-like papillomavirus particles (VLPs) produced in eukaryotic cells by expression of the late region and used as vaccines. (Courtesy of lan Frazer,

MD, Princess Alexandra Hospital, University of Queensland, Australia.)

Figure 22-25Approximate quantitative changes in seven morphologic criteria found to be most useful in dating human endometrium. (Modified from Noyes RW: Normal phases of the

endometrium. In Norris HJ, et al (eds): The Uterus. Baltimore, Williams & Wilkins, 1973.)

Figure 22-26Histology of the menstrual cycle, including the proliferative phase with mitoses (A), the early secretory phase with subnuclear vacuoles (B) followed by secretory exhaustion

(C), predecidual changes (D), stromal granulocytes (E), and stromal breakdown at the onset of menses (F) (see text).

TABLE 22-2-- Causes of Abnormal Uterine Bleeding by Age Group

Age Group Causes

Prepuberty Precocious puberty (hypothalamic, pituitary, or ovarian origin)

Adolescence Anovulatory cycle, coagulation disorders

Reproductive age Complications of pregnancy (abortion, trophoblastic disease, ectopic pregnancy)

Organic lesions (leiomyoma, adenomyosis, polyps, endometrial hyperplasia, carcinoma)

Anovulatory cycle

Ovulatory dysfunctional bleeding (e.g., inadequate luteal phase)

Perimenopausal Anovulatory cycle

Irregular shedding

Organic lesions (carcinoma, hyperplasia, polyps)

Postmenopausal Organic lesions (carcinoma, hyperplasia, polyps)

Endometrial atrophy

pituitary tumors; (2) a primary lesion of the ovary, such as a functioning ovarian tumor (granulose-theca cell tumors) or polycystic ovaries (see section on ovaries); or (3) a generalized

metabolic disturbance, such as marked obesity, severe malnutrition, or any chronic systemic disease. In most patients, however, anovulatory cycles are unexplainable, probably occurring

because of subtle hormonal imbalances. Anovulatory cycles are most common at menarche and the perimenopausal period.

Failure of ovulation results in prolonged, excessive endometrial stimulation by estrogens. Under these circumstances, the endometrial glands undergo mild architectural changes, including

cystic dilation (persistent proliferative endometrium). Unscheduled breakdown of the stroma may also occur ("anovulatory menstruation"), with no evidence of endometrial secretory

activity ( Fig. 22-27A ). More severe consequences of anovulation are discussed under endometrial hyperplasia.

Date: 2016-04-22; view: 843