Cui Dongmei. Atlas of Histology: with functional and clinical correlations. 1st ed

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CHAPTER 19

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Female Reproductive System

375

Figure 19-4A. Primordial follicles, ovary. H&E, 290;

inset 110

Primordial follicles are the smallest and most numerous

type of follicles in the cortex of the ovary. Each primordial

follicle contains a germ cell (primary oocyte) in a resting

state that may persist for as long as 50 years. The primary

oocyte is surrounded by a layer of squamous cells called

follicular cells. These follicular cells are somatic cells that

support the oocyte. The oocyte has a pale appearance

and a large nucleus with a prominent nucleolus. About

1 million follicles are present in the ovaries at the time

of birth; however, only a few hundred of these follicles

become mature. The follicles begin to grow at puberty,

and there is a constant loss of follicles throughout the

reproductive years. At menopause, only a few follicles

remain.

Squamous

follicular cells

Squamous

follicular cells

Primordial

follicles

Primordial

follicle

Primordial

follicles

Primordial

follicle

Follicular

cells

Follicular

cells

Basal lamina of follicle

Nucleus of primary oocyteNucleus of primary oocyte

Nucleus of

primary oocyte

Nucleus of

primary oocyte

Mitochondria of primary oocyte

Mitochondria of

follicle cells

Mitochondria of

follicle cells

Granules in oocyte

Nucleus of follicular cell

Nucleus of stromal cell

Junction between

follicular cells

Junction between

follicular cells

Figure 19-4B. Primordial follicle. EM, 3,900; inset (color) H&E, 500

The primary oocyte at the center of this primordial follicle may appear to be in interphase of the cell cycle, but it is arrested in dictyo-

tene of prophase I of meiosis. What appear to be patches of heterochromatin in the nucleus are partially decondensed tetrads com-

posed of paired homologous chromosomes. The oocyte has been in prophase of meiosis I before birth of the individual. Follicular

cells form a simple squamous epithelium that surrounds the oocyte. Note that these cells adhere tightly to the surface of the oocyte.

Indeed, there are junctions between the oocyte and the follicle cells, although they are not readily identiﬁ able here. Neighboring fol-

licular cells are also connected by junctional complexes, and there is a basal lamina between the follicular cells and the surrounding

interstitial tissue of the ovarian cortex.

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Organ Systems

Figure 19-5A. Primary follicles, ovary. H&E, 202; inset

438

Primary follicles develop from primordial follicles. Each primary

follicle consists of a primary oocyte and cuboidal follicle cells.

These follicle cells increase in height (from squamous cells to

cuboidal cells), and their cellular layers gradually increase as the

follicle continues to grow. At this stage, follicle cells are called

granulosa cells, because their cytoplasm begins to have a granu-

lar appearance. The primary follicles can be classiﬁ ed into unil-

aminar primary follicles and multilaminar primary follicles. The

unilaminar primary follicle has a single layer of cuboidal granu-

losa cells with a smaller oocyte. The multilaminar primary fol-

licle has several layers of cuboidal granulosa cells surrounding a

relatively large oocyte. As the oocyte increases its size, the zona

pellucida emerges as an amorphous layer between the surface

of the oocytes and the surrounding granulosa cells (Fig. 19-5B).

Situated outside of the basement membrane of the granulosa

cells are stromal cells that ﬂ atten and develop into a sheath that

surrounds the follicle; this layer is called the theca folliculi.

Cuboidal follicle cells

of primary

(unilaminar) follicle

Cuboidal follicle cells

of primary

(unilaminar) follicle

Primordial

follicle

Primordial

follicle

Germinal

epithelium

Germinal

epithelium

Zona

pellucida

Zona

pellucida

Oocyte

Primary

oocyte

Granulosa

cells

Theca

folliculi

Primordial

follicle

Zona pellucida

Granulosa cells

Microvilli

Theca folliculi

Cytoplasm of oocyte

Figure 19-5B. Growing (primary) follicle. EM, 3,200; inset (color) H&E, 152

The oocyte in the center of this growing follicle has been sectioned off center so that the nucleus is not shown. Although the oocyte has

begun to grow, it is still arrested in prophase of meiosis I. Note the membrane-bound vesicles in the cytoplasm of the oocyte; these will

participate in the cortical granule reaction if the oocyte becomes fertilized. The follicle cells that surrounded the oocyte have prolifer-

ated and transformed into granulosa cells. At this stage, the granulosa comprises about two layers of cuboidal cells. The inner granu-

losa cells no longer have smooth close contact with the surface of the oocyte because a layer of amorphous extracellular material, the

zona pellucida, has developed. As the granulosa cells continue to proliferate, several layers of cells will accumulate, and ultimately,

a ﬂ uid-ﬁ lled space, the antrum, will develop. Changes are also underway in the stroma adjacent to the growing follicle. The stromal

cells (ﬁ broblasts) have become concentrated and ﬂ attened against the basal lamina of the granulosa. These theca folliculi cells will

develop properties of steroid hormone–synthesizing cells if development of the follicle continues.

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377

Figure 19-6A. Secondary follicles, ovary. H&E,

108; inset 211

The secondary follicle develops from the continued

growth of the multilaminar primary follicle.

Spaces ﬁ lled with follicular ﬂ uid (liquor folliculi)

appear among the granulosa cells within the sec-

ondary follicle. These spaces gradually merge to

form a single large space called the antrum. The

zona pellucida is distinct, and the theca folliculi

(surrounding the follicle) develops into the theca

interna and theca externa. The theca interna

is the inner vascular layer containing cuboidal

(steroid-producing) secretory cells. These cells

secrete androgens, which diffuse into the granu-

losa cells where they are converted into estrogens

in response to FSH. The theca externa is an outer

connective tissue layer containing mainly colla-

gen and some small squamous cells mixed with a

few smooth muscle cells.

Primary

oocyte

Primary

oocyte

Secondary

follicle

Secondary

follicle

Antrum

Granulosa

cells

Granulosa

cells

Zona

pellucida

Zona

pellucida

Theca

interna

Theca

interna

Theca

externa

Theca

externa

Granulosa cells

Theca interna

Theca externa

Cumulus

oophorus

Corona radiata

Nucleus of oocyte

Zona pellucida

Blood

vessel

Blood

vessel

Cumulus oophorus

Antrum

Primary

follicle

Primary

follicle

Membrana granulosa

ranulosa cells)

Membrana granulosa

(granulosa cells)

Corona

radiata

Corona

radiata

Oocyte

Cumulus

oophorus

Cumulus

oophorus

Theca interna

Theca externa

Figure 19-6B. Graaﬁ an follicles, ovary. H&E, 54; inset (upper) 429; inset (lower) 178

The Graaﬁ an follicle is a mature follicle; it is also called a preovulatory follicle. At this stage, the follicle has grown to a large size

(about 25 mm) and bulges from the surface of the ovary. The decreased number of granulosa cells and increased volume of ﬂ uid in

the antrum result in the oocyte being located at the periphery of the follicle. The membrana granulosa is formed by multiple cellular

layers of granulosa cells lining the inner wall of the antrum. Some granulosa cells form a hillock called the cumulus oophorus, which

supports and houses the oocyte. The inner granulosa cells of the cumulus oophorus form a single layer called the corona radiata,

which immediately surrounds the oocyte. As the follicle grows, most of the granulosa cells gradually loosen from the cumulus

oophorus, but the corona radiata remains in contact with the oocyte. Eventually, the oocyte, with the corona radiata, ﬂ oats freely in

the antrum before ovulation. The oocyte remains as a primary oocyte in the graaﬁ an follicle until pituitary secretion of LH increases

sharply (LH surge); this stimulates the primary oocyte to complete the ﬁ rst meiotic division and become a secondary oocyte. The

secondary oocyte with the corona radiata and polar body (from the ﬁ rst oocyte division) are released from the graaﬁ an follicle of the

ovary. After the secondary oocyte reaches the ampulla of the oviduct, the second meiotic division occurs, if fertilization takes place.

A spermatozoan must penetrate the corona radiata and zona pellucida to complete the fertilization process. The upper inset shows

the theca folliculi (theca interna and theca externa). The lower inset shows the oocyte surrounded by granulosa cells.

The ovarian cycle is under the control of the hormones FSH and LH produced by the gonadotrophs of the anterior pituitary

gland. FSH stimulates estrogen production and follicular growth; LH stimulates meiotic division of the primary oocyte, ovulation,

and development of the corpus luteum. The estrogens play an important role in the stimulation of follicle growth by promoting

proliferation of the granulosa cells, and they also stimulate the mammary glands to prepare for lactation.

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Organ Systems

Ovulated

secondary oocyte

Corpus

albicans

Corpus luteum

Theca

lutein cells

Theca

lutein cells

Theca

lutein cells

Theca

lutein cells

Granulosa

lutein cells

Granulosa

lutein cells

Nuclei of granulosa

lutein cells

Nuclei of granulosa

lutein cells

Cytoplasm of

granulosa lutein cells

Cytoplasm of

granulosa lutein cells

Blood

vessels

Blood

vessels

Connective

tissue

Connective

tissue

Blood

vessels

Blood

vessels

Corpus albicans

Figure 19-7A. Corpus luteum, ovary. H&E, 36; insets 363

After ovulation, the remaining portion (wall) of the graaﬁ an

follicle transforms into the corpus luteum (yellow body). The wall

of the corpus luteum is folded and contains granulosa lutein cells

(derived from granulosa cells) and theca lutein cells (from the theca

interna). The granulosa lutein cells are large and have pale cyto-

plasm; these cells have features of steroid hormone–producing cells,

and they produce primarily progesterone. The theca lutein cells are

smaller but also have features of steroid hormone–secreting cells;

these cells secrete primarily progesterone and androgens.

Figure 19-7B. Corpus albicans, ovary. H&E, 34

In the absence of fertilization, the corpus luteum is active only for a

short period of time (10–14 days). The corpus luteum degenerates,

decreases in size, and forms a structure called the corpus albicans.

The corpus albicans consists of dense connective tissue that appears

as a white scar; it gradually decreases in size and remains in the ovary

for months to years. However, if fertilization and implantation occur,

the corpus luteum is rescued from degeneration by human chorionic

gonadotropin (hCG) hormone from the placenta. During pregnancy,

the corpus luteum will remain active for the ﬁ rst 6 months of gesta-

tion, after which it degenerates, and the corpus albicans is formed.

Formation of the corpus luteum is stimulated by the LH surge.

CLINICAL CORRELATION

Figure 19-7C.

Granulosa Cell Tumor. H&E, 52

Granulosa cell tumor of the ovary is a neoplasm composed of ovar

ian granulosa and, occasionally, theca cells. Granulosa cell tumors

may arise at any age and are divided into juvenile and adult types.

These tumors may produce excess estrogen, the result of which

may cause precocious puberty, endometrial hyperplasia, and endo-

metrial cancer. Symptoms may include abdominal pain, hemoperi-

toneum with hypotension, and mimicking an ectopic pregnancy in

younger patients because of rupture of the tumor. Histologically,

the tumor cells are small and cuboidal, and may be arranged in a

variety of patterns including solid, trabecular, and cordlike. The

tumor cells often contain a groove resembling a coffee bean. Small

follicle-like structures named Call-Exner bodies may be visible in

well-differentiated tumors. The behavior of granulosa cell tumors

is variable and may take an aggressive course in some patients.

A total abdominal hysterectomy and bilateral salpingo-oophorec-

tomy are the treatments of choice in the early stage.

Granulosa cell

tumor with

neoplastic

cells arranged

in cords

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379

Figure 19-8. Events of the female reproductive cycle.

The following sequence of events refer to the numbered events labeled in red in the diagram above. (1) At the beginning of the female

reproductive cycle, there are rising levels of gonadotropic hormones from the anterior pituitary, most importantly FSH. (2) This rise

promotes ovarian recruitment of a cohort of antral follicles to proceed into advanced development and then selection of typically a

single dominant follicle at about day 6. (3) These follicles secrete steroid hormones, most prominently estrogens, that (4a) promote

rebuilding of the endometrium (proliferative phase) and (4b) exert a negative feedback on FSH secretion by pituitary gonadotropes.

(5) In the latter part of the follicular phase, the dominant follicle secretes increasing amounts of estrogens (and, to a lesser extent,

progesterone). (6) When circulating estrogen reaches a threshold level (about 200 pg/mL) for a duration of about 36 hours, pituitary

gonadotropes are stimulated to sharply increase secretion of gonadotropic hormones––most importantly, LH. (7) This LH surge

from the pituitary brings about ﬁ nal maturation of the dominant follicle culminating in ovulation (about 40 hours after initiation

of the LH surge) and formation of the corpus luteum from the remaining components of the follicle. (8) The corpus luteum secretes

progesterone as well as estrogens. (9a) This induces a change in the endometrium from the proliferative phase to the secretory phase.

(9b) Meanwhile, gonadotropin secretion is greatly reduced, probably because of negative feedback effects of the high progesterone

and estrogen levels coming from the corpus luteum. (10) Without LH support, the corpus luteum fails after about 10 days, and ste-

roid hormone levels fall. (11a) This loss of steroid hormone support results in degenerative changes in the endometrium culminating

in menstruation. (11b) The fall in progesterone also releases the pituitary gonadotropes from negative feedback with the result that

FSH secretion starts to rise toward the end of the cycle, and this starts another round of follicle recruitment.

J. Naftel

Day of nominal female reproductive cycle

71421

Progesterone

Estradiol

FSH

Pituitary

gonadotroph

hormones

Ovarian

steroid

hormones

Ovary

Endometrium

Hormone concentration in plasma

(1)

(2)

(3)

(4a)

(4b)

(9b)

(9a)

(5)

(6)

(7)

(8)

(10)

(11a)

(11b)

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Organ Systems

Oviducts (Fallopian Tubes)

Lumen

Mucosa

Muscularis

Serosa

Peg cells

Lamina propria

Cilia

Ciliated cells

Cilia

Microvilli

Basal bodies

Nucleus of

ciliated cell

Basal lamina

Figure 19-9A. Oviduct (fallopian tube). H&E, left 17; right 680

The oviduct (fallopian tube) can be divided into four regions: the infundibulum, ampulla, isthmus, and intramural portion (Fig. 19-1).

The infundibulum is a funnel-shaped opening that has a fringe of tentacle-like extensions called ﬁ mbriae. The ampulla has a rela-

tively large, labyrinthine lumen where fertilization usually takes place. The isthmus is a narrow portion of the oviduct, close to the

uterus. The intramural portion is the terminal segment and is located within the uterine wall. The wall of the oviduct consists of a

mucosa (simple columnar epithelium and lamina propria), muscularis (inner circular and outer longitudinal smooth muscle), and

serosa. The epithelium of the oviduct contains ciliated cells and peg cells. The cells vary in height according to hormonal stimula-

tion. The oviduct provides an ideal environment for the fertilization of the oocyte and initial development of the embryo as well

as transportation of the zygote (fertilized oocyte) to the uterus. On the left is a low-magniﬁ cation view of the ampulla; on the right

is a higher magniﬁ cation view of the mucosa. Ciliated cells help sweep the oocyte toward the uterus. Each ciliated cell has a pale

appearance with many cilia on its apical surface. These cells have a large nucleus and a fair amount of cytoplasm. Peg cells are

secretory cells that produce nutrient-rich secretions to nourish and protect the oocyte and promote fertilization. They are small

in size and interspersed among the ciliated cells.

Figure 19-9B. Epithelial cells lining the

oviduct. EM, 8,900

The simple columnar epithelium that lines

the oviduct is composed of two cell types

(ciliated cells and peg cells); only ciliated cells

are shown here. These ciliated cells func-

tion, along with smooth muscle of the mus-

cularis, in mixing the contents (gametes) of

the lumen and in transporting the oocyte and

zygote at a precisely controlled rate along the

length of the lumen of the oviduct. The num-

ber and activity of cilia change in response

to changes in the levels of steroid hormones

throughout the reproductive cycle, reaching

a peak at the time of ovulation when estro-

gens dominate. Note that these cells also bear

numerous microvilli, suggesting an additional

absorptive function.

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381

Figure 19-10A. Menstrual phase of the endome-

trium, uterus (days 1–4 of the cycle). H&E, 13;

insets 93

The wall of the uterus includes the endometrium, the

myometrium, and serosa. The endometrium, the mucosa

of the uterus, is composed of a surface epithelium and

simple tubular uterine glands within a stroma of con-

nective tissue. The endometrium consists of the basalis

(basal layer) and the functionalis (functional layer). The

functionalis is near the lumen and undergoes changes

during the menstrual cycle. During the menstrual phase,

the functionalis sloughs off as a result of ischemia and

necrosis caused by contraction of the coiled arteries.

This occurs when fertilization does not take place and

the corpus luteum atrophies, causing the levels of estro-

gen and progesterone to fall. The menstrual phase is the

initial stage of the menstrual cycle; the endometrium

will begin to recover at the end of the menstrual phase.

Endometrium

Myometrium

Functionalis

Basalis

Sloughed

gland

Sloughed

gland

Uterine

glands

Uterine

glands

Myometrium

Arteries in the

myometrium

Arteries in the

myometrium

Endometrium

Luminal surface

Basalis

Straight

uterine glands

Straight

uterine glands

Straight

uterine glands

Straight

uterine glands

Mitotic

figures

Mitotic

figures

Lumen of

gland

Lumen of

gland

Glandular epithelium

Myometrium

Luminal

surface

Luminal

surface

Endometrium

Myometrium

Basalis

Functionalis

Uterine

glands

Uterine

glands

Lumen of

uterine glands

Lumen of

uterine glands

Coiled arteries

Stroma

Lumen of

uterine gland

Lumen of

uterine gland

Uterus

Figure 19-10B. Proliferative phase of the endome-

trium, uterus (days 5–14 of the cycle). H&E, 18;

inset (upper) 68; inset (lower) 293

The proliferative phase follows the menstrual phase.

The epithelium, uterine glands, and connective tissue

of the functionalis are rebuilt by proliferation and dif-

ferentiation of cells that remained in the basalis. At this

stage, the uterine glands are straight and have narrow

lumens as shown here; the surface of the endometrium

is smooth. The epithelial lining of the uterine glands

commonly appears as pseudostratiﬁ ed columnar

epithelium because of proliferation of the lining cells.

Mitotic ﬁ gures are occasionally seen (inset). The glands

open onto the luminal surface of the uterus. During the

proliferative phase, the changes in the endometrium are

driven by estrogens that are produced by the granulosa

cells of the developing follicles.

Figure 19-10C. Secretory phase of the endome-

trium, uterus (days 15–28 of the cycle). H&E, 14;

insets 89

The secretory phase begins shortly after ovulation occurs.

It is inﬂ uenced by progesterone produced by the corpus

luteum. At this stage, the endometrium becomes thick-

est (6–7 mm), and the uterine glands are coiled and have

large sacculated lumens. The upper inset shows tortuous

glands with large, irregular, sawtooth-shaped lumens.

The lower inset shows coiled arteries found in the endo-

metrial stroma. These coiled arteries are also called spiral

arteries and extend transiently from the basalis into the

functionalis of the endometrium. The coiled arteries arise

from arcuate arteries of the myometrium. During the

secretory phase, these spiral arteries become elongated

and highly coiled and extend into the functionalis of

the endometrium. The arcuate arteries also give rise to

straight arteries that permanently supply the basalis.

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Organ Systems

D.Cui

Morula

Zona

pellucida

Blastomeres

(subdivided zygote)

Trophoblast

Cytotrophoblast

Blastocyst

cavity

(blastocoel)

Inner cell

mass

(embryoblast)

Syncytiotrophoblast

Bilaminal

embryonic disc

Blastocyst

Implantation

Blastocyst

cavity

Amniotic

cavity

Implantation

site

Uterine

glands

Uterine

glands

Endometrium

Figure 19-11A. Implantation, endometrium of the uterus. H&E, 8

After an ovum has been successfully fertilized by a spermatozoan in the ampulla of the oviduct, the zygote (fertilized oocyte)

undergoes mitotic cell division (cleavage) and becomes a multicellular structure called the morula. The morula develops into the

blastocyst, which is transported into the uterus. The process of the blastocyst attaching to the endometrium of the uterus is called

implantation. Implantation occurs at the end of the secretory phase; the endometrium during this period of time is also called the

premenstrual endometrium (days 25–28). Implantation usually occurs on the posterior wall of the body of the uterus. If implanta-

tion succeeds, the trophoblast differentiates into two cell layers: an inner cytotrophoblast layer and an outer syncytiotrophoblast

layer. The syncytiotrophoblast attaches to and invades the endometrium of the uterus, and the process of placentation begins. hCG

secreted by the placenta stimulates the corpus luteum to remain active and continue to secrete estrogen and progesterone during the

pregnancy. The photomicrograph on the left shows an implantation site enclosed within the connective tissue of the endometrium.

CLINICAL CORRELATIONS

Figure 19-11B.

Endometrial Adenocarcinoma. H&E, 48

Endometrial adenocarcinoma is the most common form of endometrial

cancer, accounting for approximately 80% of cases. The majority of cases

of endometrial adenocarcinoma arise in the setting of elevated levels of

estrogen unopposed by the action of progesterone, causing endometrial

hyperplasia. Some cases, however, arise in postmenopausal women with

atrophy of the endometrium. Excess or unopposed estrogen may be due to

chronic anovulation, obesity, ovarian granulosa cell tumors, or exogenous

hormone intake. In the early stage, the cancer is usually asymptomatic.

Common symptoms include vaginal bleeding, menorrhagia, metrorrhagia,

and lower abdominal pain. Histologically, the cancer is characterized by

the presence of cells resembling the glandular cells of the endometrium,

and range from well differentiated with gland formation to poorly differ-

entiated with solid sheets of neoplastic cells. Endometrial biopsy is widely

used in the diagnosis of the cancer. Treatment options include surgical

removal of the uterus, radiation therapy, and chemotherapy.

Figure 19-11C.

Uterine Leiomyoma. H&E, 95

Uterine leiomyoma, or ﬁ broid, is a benign neoplasm, derived from smooth

muscle cells of the uterine myometrium. Leiomyomas represent the most

common benign neoplasm in women, and occur more frequently in African

Americans. Leiomyomas occur in the reproductive years when estrogen levels

are high, and tend to regress during menopause. Most patients with ﬁ broids

are asymptomatic, but, as the tumor enlarges, symptoms may include abnor-

mal bleeding, menorrhagia, lower abdominal pain, and increased urinary

frequency. Grossly, leiomyomas are well circumscribed and may be in sub-

serosal, intramural, or submucosal locations. Leiomyomas can be single but

are often multiple and may become quite large. The cut surface is typically

white to tan, with a whorled, bulging appearance. Histologically, the tumor

cells appear as well- differentiated, spindle-shaped smooth muscle cells, often

with increased extracellular matrix, such as collagen, proteoglycan, and

ﬁ bronectin. Leiomyomas rarely become their malignant counterpart, leio-

myosarcomas, which usually develop de novo. Treatment options include

hysterectomy, myomectomy (removal of the ﬁ broid), and hormone therapy.

Adenocarcinoma

invading the

myometrium

Fascicles o

smooth

muscle

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383

Figure 19-12A. Cervix. H&E, 17; inset 350

The inferior part of the uterus forms the cervical canal, which bulges

into the vagina. The internal os is the opening from the endocervical

canal to the uterus; the external os is the opening to the vaginal canal.

The surface of the endocervix is lined by simple columnar epithelium,

which consists of mucus-secreting cells (inset); the ectocervix is lined

by stratiﬁ ed squamous epithelium. The cervix contains long branched

mucous glands known as cervical glands; when these glands become

obstructed they form cervical cysts (nabothian cysts). The secretion

of the cervix changes depending on the stage of the menstrual cycle;

however, the mucosa of the cervix does not slough off as does the

endometrium of the uterus. The cervical stroma is composed of dense

connective tissue mixed with a small amount (about 15%) of smooth

muscle. Usually, the cervix has a narrow canal; however, during deliv-

ery, dilation of the cervix allows the baby to pass through the canal.

Branched

cervical

glands

Cervical

cysts

Internal os

Endocervical

canal

Ectocervix

Stratified

squamous

epithelium

(ectocervix)

External os

Cervix

Cervical stroma

Simple columnar

epithelium

(endocervix)

Simple columnar

epithelium

(endocervix)

Endocervix

The cervical transformation (transition) zone is the area of the

cervical mucosa between the original squamocolumnar junction

and the restored or new squamocolumnar junction that is formed

through the processes of squamous metaplasia and squamous

epithelialization. The majority of cervical carcinomas arise in this

zone, and it is important that this area be sampled during screening

with a Papanicolaou smear.

CLINICAL CORRELATION

Figure 19-12B.

Cervical Cancer. H&E (upper left), 20; (lower right), 115

Cervical cancer is a malignant neoplasm of the uterine cervix, the major

ity of which are squamous cell carcinomas. Risk factors include the early

onset of sexual activity, multiple sexual partners, and exposure to human

papillomavirus (HPV). Invasive squamous cell carcinoma is preceded by

precursor lesions called cervical intraepithelial neoplasia, in which dysplas-

tic epithelial changes are present. The majority of intraepithelial lesions

are related to infection by HPV. The introduction of screening using the

Papanicolaou smear, or “Pap” smear, has dramatically reduced the inci-

dence of invasive cervical lesions. Symptoms of cervical cancer include

abnormal vaginal bleeding, postcoital bleeding, and vaginal discharge. His-

tologically, the cancer typically arises in the cervical transformation zone

and may show superﬁ cial ulceration with endophytic or exophytic growth

patterns. The cancer can spread by direct invasion to nearby tissues and

organs or metastasize through hematogenous or lymphatic routes. Garda-

sil, a vaccine against certain HPV types, is used in young women to prevent

infection by the virus. Treatment options include surgical removal of the

uterus (hysterectomy), radiation therapy, and chemotherapy.

Squamous

epithelium

Squamous cell

carcinoma

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384

UNIT 3

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Organ Systems

Figure 19-13A. Overview of the placenta. H&E, left 13; left inset 55; right (upper) 704; right (lower) 748

The placenta consists of the maternal portion and the fetal portion. It is a temporary organ that provides a bridge for exchanging

gases, nutrients, hormones, and other materials between the maternal and fetal blood circulations. The maternal portion is the

decidua basalis. The fetal portion consists of the chorionic plate (Fig. 19-11A), chorionic villi, and cytotrophoblastic shell. Fetal

blood ﬂ ows within the blood vessels of the chorionic villi; maternal blood is contained within the intervillous space. The placental

barrier prevents the fetal blood from mixing with the maternal blood. The decidua basalis forms when stromal ﬁ broblasts of the

endometrium are transformed into decidual cells at the site of implantation. The syncytiotrophoblast invades the maternal blood

vessels replacing smooth muscle in the vessel walls. Syncytiotrophoblasts also line the surface of the intervillous space. The cytotro-

phoblast forms an interface (cytotrophoblastic shell) between the maternal and fetal tissues.

Decidual cell

Cells in

cytotrophoblastic shell

Cells in

cytotrophoblastic shell

Fetal blood cells

within the chorionic villus

Fetal blood cells

within the chorionic villus

Chorionic

plate

Amniotic

cavity

Floating

chorionic

villus

Floating

chorionic

villus

Intervilluus space

Intervillous space

Fetal

portion

Fetal

portion

Maternal portion

(decidua basalis)

Maternal portion

(decidua basalis)

Anchoring

villus

Anchoring

villus

Decidua

basalis

Decidua

basalis

Cytotrophoblastic

shell

Cytotrophoblastic

shell

Chorionic

villus

Chorionic

villus

Stem

villus

Stem

villus

Chorionic plate

Fetal blood vessel

Syncytiotrophoblast

Intervillous

space

Intervillous

space

Amniotic cavity

Cytotrophoblast

Maternal blood in the

intervillous space

Maternal blood in the

intervillous space

Chorionic villus

Figure 19-13B. Fetal portion of the placenta. H&E, left 18; right 136

The chorionic plate consists of connective tissue and forms the wall of the amniotic cavity; it contains chorionic arteries and veins. The

chorionic villi can be classiﬁ ed on the basis of their developmental stages: (1) Primary chorionic villi are newly formed villi at an early

stage (about the second week of implantation), and consist of only a trophoblast layer. (2) Secondary chorionic villi develop at the end of

the second week when mesenchymal tissue grows into the villi and forms a mesenchymal core within the trophoblastic shell. (3) Tertiary

chorionic villi develop at the third week, at which time the fetal blood and blood vessels are formed within the chorionic villi. By the end of

the third week, the fetal blood begins to ﬂ ow, and gas and nutrient exchange takes place between the fetal and maternal blood by diffusion

through the placental barrier. The placental barrier is composed of the syncytiotrophoblast, cytotrophoblast, connective tissue of the villus,

endothelium of the fetal capillary, and the basement membranes of the trophoblast and endothelium. The syncytiotrophoblast produces

hCG hormone, which plays an important role in maintaining pregnancy via stimulation of the corpus luteum to secrete progesterone.

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