Female Genital Tract of the OVARY

Question 1

The most common types of lesions encountered in the ovary include_________________.

I

Answer 1

functional or benign cysts
and tumor

Question 2

__________________ovary (oophoritis) are uncommon, and usually accompany tubal inflammation.

Answer 2

Intrinsic inflammations

Question 3

Rarely, a__________________ involving ovarian
follicles (autoimmune oophoritis) occurs and is associated with **infertility. **

Answer 3

** primary inflammatory disorder**

Question 4

The ovary has three
main histologic compartments:

Note: Each compartment gives rise to distinct non-neoplastic and
neoplastic entities, as discussed below.

Answer 4

(1) the surface müllerian epithelium,
(2) the germ cells, and
3) the sex cord–stromal cells.

Question 5

Non-Neoplastic and Functional Cysts

Answer 5

FOLLICLE AND LUTEAL CYSTS

POLYCYSTIC OVARIES AND STROMAL HYPERTHECOSIS

Question 6

FOLLICLE AND LUTEAL CYSTS
______________in the ovary are so common that they are considered virtually normal.

They

• *originate in unruptured graafian follicles** or in follicles that have ruptured and immediately
• *sealed**

Answer 6

Cystic follicles

Question 7

These cysts are usually multiple. They range in size up to 2 cm in diameter, are filled with a clear serous fluid, and are lined by a gray, glistening membrane.

On occasion, larger cysts exceeding 2 cm (follicle cysts) may be diagnosed by palpation or ultrasonography; these may cause pelvic pain. Granulosa lining cells can be identified
histologically if the intraluminal pressure has not been too great. The outer theca cells may be conspicuous due to increased amounts of pale cytoplasm (luteinized). As discussed subsequently, when this alteration is pronounced (hyperthecosis), it may be associated with
increased estrogen production and endometrial abnormalities.

Answer 7

cystic follicle

Question 8

_________________are normally present in the ovary.

These cysts are
lined by a rim of bright yellow tissue containing luteinized granulosa cells.

They occasionally
ruptureandcause a peritoneal reaction.

Sometimes the combination of old hemorrhage and
fibrosismaymake their distinction from endometriotic cysts difficult.

Answer 8

Granulosa luteal cysts (corpora lutea)

Question 9

____________________ affects 3% to 6%
of reproductive-age women.

The central pathologic abnormality is numerous cystic follicles or
follicle cysts, oftenassociated with oligomenorrhea.

Women with PCOD have persistent
anovulation,obesity (40%),hirsutism (50%), and, rarely, virilism

Answer 9

Polycystic ovarian disease (PCOD; formerly termed SteinLeventhal syndrome)

Question 10

The ovaries are usually twice normal size and have a smooth, gray-white outer
cortex studded with subcortical cysts 0.5 to 1.5 cm in diameter.

On histologic examination,
there is a thickened, fibrotic superficial cortex beneath which are innumerable follicle cysts
associated with hyperplasia of the theca interna (follicular hyperthecosis) ( Fig. 22-34 ).
Corpora lutea are frequently but not invariably absent.
Non-Neoplastic & Functional Cysts
2006

Answer 10

Polycystic ovarian disease

Question 11

Polycystic ovarian disease and cortical stromal hyperplasia.

A, The
ovarian cortex reveals numerous clear cysts.

B, Sectioning of the cortex reveals several
subcortical cystic follicles.

C, Cystic follicles seen in a low-power microphotograph.

D,Cortical stromal hyperplasia manifests as diffuse stromal proliferation with symmetric
enlargement of the ovary.

Answer 11

GET THE PIC

Question 12

The initiating event in PCOD is not clear.

Increased secretion of luteinizing hormone may
stimulate the theca-lutein cells of the follicles, to produce excessive androgen
(androstenedione), which is converted to estrone.

For years, these endocrine abnormalities
were attributed to primary ovarian dysfunction because large wedge resections of the ovaries
sometimes restored fertility. It is now believed that a variety of enzymes involved in androgen
biosynthesis are poorly regulated in PCOD.

Recent studies link PCOD, like type 2 diabetes, to
insulin resistance. Treatment of the insulin resistance sometimes results in resumption of
ovulation.

Question 13

_______________, is a disorder of ovarian stroma
most commonly seen in postmenopausal women, but it may blend with PCOD in younger
women.

The disorder is characterized by uniform enlargement of the ovary (up to 7 cm), which
has a white to tan appearance on sectioning.

The involvement is usually bilateral and
microscopically shows hypercellular stroma and luteinization of the stromal cells, which are
visible as discrete nests of cells with vacuolated cytoplasm. The clinical presentation and effects
on the endometrium are similar to those of PCOD, although virilization may be striking.

Answer 13

Stromal hyperthecosis, also called cortical stromal hyperplasia,

Question 14

A physiologic condition mimicking the above syndromes is________________. In response to pregnancy hormones (gonadotropins), proliferation of theca cells
and expansion of the perifollicular zone occurs. As the follicles regress, the concentric thecalutein
hyperplasia may appear nodular. This change is not to be confused with true luteomas of
pregnancy

Answer 14

theca lutein hyperplasia of
pregnancy

Question 15

There are numerous types of_____________ and overall they fall into benign, borderline, and
malignant categories.

About 80% are benign, and these occur mostly in young women between
the ages of 20 and 45 years.

Borderline tumors occur at slightly older ages.

Malignant tumors
are more common in older women, between the ages of 45 and 65 years.

Ovarian cancer
accounts for 3% of all cancers in females and is the fifth most common cause of death due to
cancer in women in the United States.

Among cancers of the female genital tract, the incidence
of ovarian cancer ranks below only carcinoma of the cervix and the endometrium.

In addition,
because most ovarian cancers are detected when they have spread beyond the ovary, they
account for a disproportionate number of deaths from cancer of the female genital tract.

Answer 15

Ovarian Tumors

Question 16

Classification.
The classification of ovarian tumors given in Table 22-5 and Figure 22-35 is a simplified version
of the World Health Organization Histological Classification, which separates ovarian neoplasms
according to the most probable tissue of origin.

It is now believed that tumors of the ovary arise
ultimately from one of three ovarian components:

Answer 16

(1) surface epithelium derived from the
* *coelomic epithelium**;

(2) the germ cells, which migrate to the ovary from the yolk sac and are
pluripotent; and

(3) the stroma of the ovary, including the sex cords, which are forerunners of
the endocrine apparatus of the postnatal ovary.

Question 17

There is also a group of tumors that defy
classification, and finally there are __________________

Answer 17

secondary or metastatic tumors to the ovary.

Question 18

TABLE 22-5 – WHO Classification of Ovarian Neoplasms

Answer 18

1. SURFACE EPITHELIAL-STROMAL TUMORS
2. SEX CORD–STROMAL TUMORS
3. GERM CELL TUMORS
4. MALIGNANT, NOT OTHERWISE SPECIFIED
   METASTATIC CANCER FROM NONOVARIAN PRIMARY

Question 19

SURFACE EPITHELIAL-STROMAL TUMORS

Answer 19

1. Serous tumors
2. Mucinous tumors, endocervical-like and intestinal
   type
3. Endometrioid tumors
4. Clear cell tumors
5. Transitional cell tumors
6. Epithelial-stromal

Question 20

Serous tumors

Answer 20

1. Benign (cystadenoma)
2. Borderline tumors (serous borderline

tumor)

1. Malignant (serous adenocarcinoma)

Question 21

Mucinous tumors, endocervical-like and intestinal
type

Answer 21

1. Benign (cystadenoma)
2. Borderline tumors (mucinous borderline

tumor)

1. Malignant (mucinous adenocarcinoma)

Question 22

Endometrioid tumors

Answer 22

Benign (cystadenoma)
Borderline tumors (endometrioid borderline
tumor)
Malignant (endometrioid adenocarcinoma)

Question 23

Clear cell tumors

Answer 23

Benign
Borderline tumors
Malignant (clear cell
adenocarcinoma)

Question 24

Transitional cell tumors

Answer 24

1. Brenner tumor
2. Brenner tumor of borderline malignancy
3. Malignant Brenner tumor
4. Transitional cell carcinoma (non-Brenner

type)

Question 25

Epithelial-stromal

Answer 25

Adenosarcoma
Malignant mixed müllerian
tumor

Question 26

SEX CORD–STROMAL TUMORS

Answer 26

1. Granulosa tumors
2. Fibromas
3. Fibrothecomas
4. Thecomas
5. Sertoli cell tumors
6. Leydig cell tumors
7. Sex cord tumor with annular

tubules

8. Gynandroblastoma
9. Steroid (lipid) cell tumors

Question 27

GERM CELL TUMORS

Answer 27

1. Teratoma

• Immature
• Mature
  
  • Solid
  • Cystic (dermoid
    cyst)
• Monodermal (e.g., struma ovarii,
  carcinoid)

2. Dysgerminoma
3. Yolk sac tumor (endodermal sinus tumor)
4. Mixed germ cell tumors

Question 28

METASTATIC CANCER FROM NONOVARIAN PRIMARY

Answer 28

Colonic,
appendiceal
Gastric
Breast
Ovarian Tumors

Question 29

Although some of the specific tumors have distinctive features and are hormonally active, most
are nonfunctionalandtend to produce relatively mild symptoms until they reach a large size.
Malignant tumors have usually spread outside the ovary by the time a definitive diagnosis is
made.

Some of these tumors, principally epithelial tumors, tend to be___________.

Table 22-6 lists
the tumors and their subtypes. Abdominal pain and distention, urinary and gastrointestinal tract
symptoms due to compression by the tumor or cancer invasion, and vaginal bleeding are the
most common symptoms.

The benign forms may be entirely asymptomatic and occasionally are
found unexpectedly on abdominal or pelvic examination or during surgery.

Answer 29

bilateral

Question 30

Most primary neoplasms in the ovary fall within this category . The classification of epithelial
tumors of the ovary is based on both differentiation and extent of proliferation of the epithelium.
T

Answer 30

TUMORS OF SURFACE (MÜLLERIAN) EPITHELIUM

Question 31

There are three major histologic types based on the differentiation of the neoplastic epithelium:
____________________. [75]

The extent of epithelial proliferation is
associated with the biologic behavior of the tumor and is classified as benign (minimal epithelial
proliferation), borderline (moderate epithelial proliferation), and malignant (marked epithelial
proliferation with stromal invasion).

Answer 31

serous, mucinous, and endometrioid tumors

Question 32

The benign tumors are often further classified based on the
components of the tumors, which may include_____________ ,_______________ and ____________

Answer 32

1. cystic areas (cystadenomas),
2. cystic and fibrous areas (cystadenofibromas), and
3. predominantly fibrous areas (adenofibromas)

Question 33

. The borderline
tumors and the malignant tumors can also have a cystic component, and when malignant they
are sometimes referred to as ________________.

The tumors can be relatively small, or they
can grow to fill the entire pelvis before they are detected.

Answer 33

cystadenocarcinomas

Question 34

The origin of ovarian epithelial tumors is, at present, unresolved.

This is in large part because
most tumors are detected relatively late, interfering with the identification of a precursor lesion.

The most widely accepted theory for the derivation of müllerian epithelial tumors is the
________________.

This view is based on the embryologic pathway by which
the müllerian ducts are formed from the coelomic epithelium and evolve into serous (tubal),
endometrioid (endometrial), and mucinous (cervical) epithelia present in the normal female
genital tract.

Such tumors are thought to occur predominantly in the ovary, because coelomic
epithelium is incorporated into the ovarian cortex to form epithelial inclusion cysts (also known
as mesothelial, cortical, or germinal inclusion cysts) ( Fig. 22-36 ). The exact mechanism by
which the cysts develop is not known, but they are thought to result from invaginations of the
surface epithelium that subsequently loses its connection to the surface. [76] The cysts are
most often lined by either mesothelial or tubal-type epithelium. The close association of ovarian
carcinomas with either the ovarian surface epithelium or inclusion cysts may explain the
development of extra-ovarian carcinomas of similar histology from coelomic epithelial rests (socalled
endosalpingiosis) in the mesentery. [75] However, this is clearly an oversimplification of
the pathogenesis of ovarian cancer

Answer 34

transformation of coelomic epithelium

Question 35

Regardless of their specific origin(s), ovarian epithelial tumors composed of serous, mucinous,
and endometrioid cell types are emblematic of the plasticity of müllerian epithelium and range
from clearly benign to malignant tumors.

[75] Several recent studies have suggested that
ovarian carcinomas may be broadly categorized into two different types based on
pathogenesis:________________

.

Answer 35

(1) those that arise in association with borderline tumors, and

(2) those that arise
as “de novo” carcinomas

Question 36

Clinicopathologic studies have shown that well-differentiated serous,
endometrioid, and mucinous carcinomas often contain areas of________________of the same
epithelial cell type, whereas this association is rarely seen for moderately to poorly
differentiated serous carcinoma or MMMTs. Recent molecular studies have provided support for
this classification scheme, as will be discussed below in the relevant sections.

Answer 36

** borderline tumors**

Question 37

These common cystic neoplasms are lined by tall, columnar, ciliated and nonciliated epithelial
cells and are filled with clear serous fluid.

Although the term serous appropriately describes the
cyst fluid, it has become synonymous with the tubal-like epithelium in these tumors.

Together
the benign, borderline, and malignant types account for about 30% of all ovarian tumors and
just over 50% of ovarian epithelial tumors. About 70% are benign or borderline, and 30% are
malignant.

Answer 37

Serous Tumors

Question 38

________________- account for approximately 40% of all cancers of the ovary and
are the** most common malignant ovarian tumors.**

Benign and borderline tumors are most
common between the ages of 20 and 45 years. Serous carcinomas occur later in life on
average, though somewhat earlier in familial cases.

Answer 38

Serous carcinomas

Question 39

Molecular Pathogenesis.
Little is known about the risk factors for the development of the benign and borderline tumors.
Risk factors for malignant serous tumors (serous carcinomas) are also much less clear than for
other genital tumors, but
_______________ play a role in tumor
development. [71,] [77]

There is a higher frequency of carcinoma in women with low parity.
Gonadal dysgenesis in children is associated with a higher risk of ovarian cancer. Women 40 to
59 years of age who have taken oral contraceptives or undergone tubal ligation have a
reduced risk of developing ovarian cancer. [78,] [79]

The most intriguing risk factors are
genetic. As discussed in Chapters 7 and 23 , mutations in both BRCA1 and BRCA2 increase
susceptibility to ovarian cancer. [71,] [77] BRCA1 mutations occur in about 5% of patients
younger than 70 years of age with ovarian cancer. The estimated risk of ovarian cancer in
women bearing BRCA1 or BRCA2 mutations is 20% to 60% by the age of 70 years.

Answer 39

nulliparity, family history, and heritable mutations

Question 40

Based on both clinicopathologic and molecular studies it has recently been proposed that
serous ovarian carcinoma be divided into two major groups:___________________ This distinction
can be made on the basis of nuclear atypia and correlates with patient survival. [80] Some lowgrade
carcinomas arise in association with serous borderline tumors, while most high-grade
carcinomas appear to arise “de novo” without a recognizable precursor lesion.

Answer 40

(1) low-grade (welldifferentiated)
carcinoma and (2) high-grade (moderately to poorly differentiated) carcinoma.

Question 41

Molecular studies of low- and high-grade serous carcinoma have revealed distinct molecular
genetic changes in the two types of carcinoma. [82]

The low-grade tumors arising in serous
borderline tumorshave mutations in the______________, withonly rare mutations in
p53

Answer 41

KRAS or BRAF oncogenes

Question 42

. In contrast, the high-grade tumors have a high frequency of mutations in the _________________ but
lack mutations in either KRAS or BRAF.

Almost all reported cases of ovarian carcinomas arising
in women with BRCA1 or BRCA2 mutations are high-grade serous carcinoma and commonly
have p53 mutations.

Answer 42

p53 gene

Question 43

Close examination of these tumors has suggested that a significant
percentage of BRCA1- and BRCA2-related tumors arise from the epithelium lining the
fimbriated end of the fallopian tube.

This finding has led investigators to speculate that at least
some sporadic high-grade ovarian and so-called ________________may
also originate from the distal fallopian tube, an area of current investigation.

Answer 43

primary peritoneal serous carcinomas

Question 44

The characteristic serous tumor may present on gross examination as either a
________________ ( Fig. 22-37A ), _______________________

Answer 44

• *cystic lesion in which the papillary epithelium** is contained within a** few fibrous walled cysts**
• *(intracystic)** or projecting from the** ovarian surface.**

Question 45

Benign tumors typically
present with a___________________

Answer 45

smooth glistening cyst wall with no epithelial thickening or with small papillary
projections

Question 46

** Borderline tumors** contain an _______________( Fig. 22-
37A and C ).

Bilaterality is common, occurring in 20% of benign serous cystadenomas, 30%
of serous borderline tumors,and approximately66% of serous carcinomas. A significant
proportion of both serous borderline tumors and malignant serous tumors involve (or
originate from) the surface of the ovary ( Fig. 22-37C ).

Answer 46

increased number of papillary projections

Question 47

On histologic examination, the cysts
are___________________ in benign tumors ( Fig. 22-38A ).
Microscopic papillae may be found.

Answer 47

** lined by columnar epithelium, which has abundant cilia**

Question 48

** Serous borderline tumors** exhibit_________________________________ ( Fig. 22-38B ). [75] This epithelial proliferation
often grows in a delicate, papillary pattern referred to as “micropapillary carcinoma” and is
thought to be the precursor to low-grade serous carcinoma ( Fig. 22-38C ).

Answer 48

** Serous borderline tumors** exhibit** increased complexity of
the stromal papillae, stratification of the epithelium and mild nuclear atypia**, but destructive
infiltrative growth into the stroma is not seen

Question 49

_____________________are important indicators of probable malignancy (see Fig. 22-37B ). These features
are characteristic of high-grade serous carcinoma, which microscopically exhibits even more
complex growth patterns and infiltration or frank effacement of the underlying stroma ( Fig.
22-38D ). The individual tumor cells in the high-grade carcinomas display marked nuclear
atypia, including pleomorphism,atypical mitotic figures, and multinucleation.

Answer 49

1. **Larger amounts of solid or papillary tumor mass, **
2. irregularity in the tumor mass,
3. **and fixation or nodularity of the capsule **

Question 50

Serous cystadenomas.

A, Papillary serous cystadenoma revealing______________

. B, Borderline serous tumor showing__________

C, Complex micropapillary growth
defines _______________

. D, Papillary serous
cystadenocarcinoma of the ovary with_________________

Answer 50

1. stromal papillae with a columnar epithelium
2. increased architectural complexity and epithelial cell stratification.
3. “micropapillary” serous carcinoma
4. invasion of underlying stroma.

Question 51

The biologic behavior of serous tumors depends on degree of differentiation, distribution, and
characteristics of the disease in the peritoneum, if present. Importantly, serous tumors may
occuron thesurface of the ovaries and, rarely, as primary tumors of the peritoneal surface,
which are referred to as primary peritoneal serous carcinoma.

Predictably,___________** **of the ovarian surface are more likely to extend to the peritoneal surfaces, and
prognosis is closely related to the histologic appearance of the tumor and its growth pattern on
the peritoneum.

Answer 51

unencapsulated
serous tumors

Question 52

________________ may arise from or extend to the peritoneal surfaces
as noninvasive implants, remaining localized and causing no symptoms, or slowly spread,
producing intestinal obstruction or other complications after many years. As discussed above,
low-grade serous carcinomas can arise in borderline serous tumors and may be associated with
what are often referred to as “invasive implants” because they demonstrate destructive,
infiltrative growth, similar to metastatic carcinoma. However, the low-grade carcinomas even
when spread outside the ovary often progress slowly,andpatients may survive for relatively
long periods before dying of disease.

Answer 52

Borderline serous tumors

Question 53

In contrast, _____________ are often widely metastatic
throughout the abdomen at the time of presentation.

These findings are associated with rapid
clinical deterioration. [75] Consequently, careful pathologic classification of the tumor, even if it
has extended to the peritoneum, is relevant to both prognosis and selection of
therapy. [75,] [83] The 5-year survival rate for borderline and malignant tumors confined within
the ovarian massis, respectively,100% and 70%,whereas the5-year survival rate for the same
tumors involving the peritoneumis about90% and 25%, respectively. Because of their
protracted course, borderline tumors may recur after many years, and 5-year survival is not
synonymous with cure.

Answer 53

high-grade tumors

**” **so mas mataas and 5 yr survival rate kapag confined lng sa ovary

Question 54

are less common than serous tumors, accounting for about 30% of all ovarian

neoplasms. They occur principally in middle adult life and are rare before puberty and after
* *menopause.**

Eighty percent are benign or borderline, and about 15% are malignant

. Primary
ovarian mucinous carcinomasare relatively uncommon and account for fewer than 5% of all
ovarian cancers.

Answer 54

Mucinous tumors

Question 55

Like serous tumors, little is known about the pathogenesis of mucinous ovarian tumors.

Most of
the studies analyzing risk factors have not segregated the different histologic types of ovarian
cancer, so it is not clear how they relate to the individual types.

However, recent studies have
suggested that mucinous tumors may have different risk factors, _______________________ which is not a risk factor of serous ovarian tumors.

Answer 55

including smoking, which is not
a risk factor for serous ovarian tumors

Question 56

Although several molecular studies have been done
over the years, very few molecular genetic alterations have been identified in mucinous tumors.
The one consistent alteration that has been identified is ________________

Answer 56

mutation of the KRAS proto-oncogene.

Note : **Mutations in KRASare common inbenign mucinous cystadenomas (58%),mucinous borderline**
tumors (75% to 86%), and in primary ovarian mucinous carcinomas (85%). [84,] [85]
Interestingly, one study showed that several tumors with distinct areas of epithelium showing
benign, borderline, and carcinoma had identical KRAS mutations from each area. [85] Thus,
KRAS mutations may occur early in the development of these neoplasms.

Question 57

1. In gross appearance, the mucinous tumors differ from the serous variety in

several ways. They are characterized by _______________l. Only 5% of primary mucinous cystadenomas and mucinous cystadenocarcinomas
are bilateral.

2. Mucinous tumors tend to______________ They appear grossly as multiloculated tumors filled

with sticky, gelatinous fluid rich in glycoproteins ( Fig. 22-39A ).

Answer 57

1. rarity of surface involvement and are less frequently

bilateral

2. produce larger cystic masses; some have been

recorded with weights of more than 25 kg.

Question 58

On histologic examination,
benign mucinous tumors are characterized by a____________________ ( Fig. 22-
39B ). One group of typically benign or borderline mucinous tumors arises in endometriosis
and is termed müllerian mucinous cystadenoma, resembling endometrial or cervical
epithelium.

Answer 58

lining of tall, columnar epithelial cells with
apical mucin and the absence of cilia, akin to benign cervical or intestinal epithelia

Question 59

The second, more common group includes tumors showing abundant glandlike or papillary growth with nuclear atypia and stratification, an appearance strikingly
similar to tubular adenomas or villous adenomas of the intestine. These tumors are presumed
precursors to most_____________

Answer 59

** **cystadenocarcinomas.

Note :​ Cystadenocarcinomas contain areas of solid
growth and conspicuous epithelial cell atypia and stratification, loss of gland architecture, and
necrosis; these tumors are similar to colonic cancer in appearance. Because both borderline
and malignant mucinous cystadenomas form complex glands in the stroma, the
documentation of clear-cut stromal invasion, which is easily ascertained in serous tumors, is
more difficult. Some authors describe a category of “noninvasive” mucinous carcinomas
(intraepithelial carcinomas) for those tumors with marked epithelial atypia without obvious
stromal alterations. [86] Approximate 10-year survival rates for stage I, noninvasive
“intraepithelial carcinomas,” and frankly invasive malignant tumors are greater than 95% and
90%, respectively. [87] Mucinous carcinomas that have spread beyond the ovary are usually
fatal, but as previously stated, these tumors are uncommon.

Question 60

A clinical condition referred to as _________________is defined by extensive mucinous
ascites, cystic epithelial implantson theperitoneal surfaces,adhesions, and frequently
mucinous tumor involving the ovaries ( Fig. 22-40 ).

Answer 60

pseudomyxoma peritonei

Question 61

______________________ are uncommon. However, endometrioid carcinomas account for approximately 20% of
all ovarian cancers.

Answer 61

Benign endometrioid tumors, called endometrioid adenofibromas, and borderline endometrioid
tumors

Question 62

Endometrioid tumors are distinguished from serous and mucinous tumors
by the ______________ bearing a close resemblance to benign or malignant
endometrium.

Answer 62

presence of tubular glands

Question 63

Endometrioid carcinomas may arise in the setting of _______________ and are
occasionally associated with areas of borderline tumor. Although these tumors are less common
than either serous or mucinous tumors, more is known about the molecular genetic alterations
associated with their development. This is due to the recent development of mouse models that
closely mimic the human disease and molecular genetic overlap with endometrioid carcinomas
of the endometrium.

n fact, 15% to 30% of ovarian endometrioid carcinomas are accompanied
by carcinoma of the endometrium,and therelatively good prognosis in such cases suggests
that the two may arise independently rather than by metastatic spread from one another.

Answer 63

endometriosis

Question 64

About 15% to 20% of cases with endometrioid carcinoma coexist with endometriosis , although
an origin directly from ovarian surface epithelium is also possible. The women with associated
endometriosisare usually about adecade younger than women with endometrioid carcinoma
that is not associated with endometriosis. Molecular studies have found relatively frequent
mutations in the PTEN tumor suppressor geneand in theKRAS and β-catenin oncogenes, as
well as microsatellite instability. [90] Similar to endometrioid carcinomas of the endometrium,

Question 65

In gross appearance, endometrioid carcinomas present as a combination of
solid and cystic areas,similar to other cystadenocarcinomas. Forty percent involve both
ovaries, and such bilaterality usually, though not always, implies extension of the neoplasm
beyond the genital tract. These are low-grade tumors that reveal glandular patterns bearing
a strong resemblance to those of endometrial origin. The 5-year survival rate for patients
with stage I tumors is approximately 75%.

Question 66

Benign and borderline clear cell tumors are exceedingly rare, and clear cell carcinomas are
uncommon. They are characterized by large epithelial cells with abundant clear cytoplasm
similar to hypersecretory gestational endometrium.

Because these tumors sometimes occur in
association with endometriosis or endometrioid carcinoma of the ovary and resemble clear cell
carcinoma of the endometrium, they are now thought to be ofmüllerian origin and variants of
endometrioid adenocarcinoma. [75] Little is currently known about the molecular alterations that
underlie the pathogenesis of these tumors. The clear cell tumors of the ovary can be
predominantly solid or cystic. In the solid neoplasm, the clear cells are arranged in sheets or
tubules. In the cystic variety, the neoplastic cells line the spaces. The 5-year survival rate is
approximately 65% when the tumors are confined to the ovaries; however, these tumors tend to
be aggressive, and with spread beyond the ovary, a survival of 5 years is exceptional.

Answer 66

Clear Cell Adenocarcinoma

Question 67

____________ are variants in which there is more pronounced proliferation of the fibrous
stroma that underlies the columnar lining epithelium. These benign tumors are usually small
and multilocular and have simple papillary processes that do not become as complicated and
branching as those found in the ordinary cystadenoma. They may be composed of mucinous,
al serous, endometrioid, and transition(Brenner tumors) epithelium.

Borderline lesions with

cellular atypia and, rarely, tumors with focal carcinoma occur, but metastatic spread of either is
extremely uncommon.

Answer 67

Cystadenofibromas

Question 68

________________are classified as adenofibromas in which the epithelial component consists of
nests of transitional-type epithelial cells resembling those lining the urinary bladder.

Less
frequently,the nests containmicrocysts or glandular spaceslined bycolumnar, mucin-secreting
cells.

Answer 68

Brenner tumors

Question 69

These neoplasms may be solid or cystic, are usually unilateral (approximately
90%), and vary in size from small lesions less than 1 cm in diameter to massive tumors up to
20 and 30 cm ( Fig. 22-41A ). The fibrous stroma, resembling that of the normal ovary, is
marked by sharply demarcated nests of epithelial cells resembling the epithelium of the
urinary tract, often with mucinous glands in their center ( Fig. 22-41B ).

Infrequently, the
stroma is composed of somewhat plump fibroblasts resembling theca cells; such neoplasms
may have hormonal activity.Most are benign, but borderline (proliferative
Brenner tumor) and malignant counterparts have been reported.

Answer 69

Brenner tumors

Question 70

___________constitute 15% to 20% of all ovarian tumors. [75] Most are benign cystic

• *teratomas**, but the remainder, which are found principally in children and young adults, have a
• *higher incidence of malignant behavior** and pose problems in histologic diagnosis and in
  therapy. They bear a remarkable similarity to germ cell tumors in the male testis ( Chapter 21 )
• *and arise in a similar manner (** Fig. 22-42 ).

Answer 70

Germ cell tumors

Question 71

Teratomas
Teratomas are divided into three categories

Answer 71

: (1) mature (benign),

(2) immature (malignant), and
(3) monodermal or highly specialized.

Question 72

Most benign teratomas are cystic and are better known in clinical parlance as dermoid cysts.
Cystic teratomasare usually found in young women during theactive reproductive years. [75]
They may be discovered incidentally, but are occasionally associated with clinically important
paraneoplastic syndromes, such as inflammatory limbic encephalitits, which may remit upon
removal of the tumor.

Answer 72

Mature (Benign) Teratomas.

Question 73

_______________are bilateral in 10% to 15% of cases. Characteristically they
are unilocular cysts containing hair and cheesy sebaceous material ( Fig. 22-43 ).

On section,
they reveal a thin wall lined by an opaque, gray-white, wrinkled epidermis. From this
epidermis, hair shafts frequently protrude. Within the wall, it is common to find tooth structures
and areas of calcification.

Answer 73

Benign teratomas

Question 74

On histologic examination the cyst wall is composed of stratified squamous epithelium with
underlying sebaceous glands, hair shafts, and other skin adnexal structures ( Fig. 22-44 ). In
most cases structures from other germ layers can be identified, such as cartilage, bone,
thyroid tissue, and neural tissues. Dermoid cysts are sometimes incorporated within the wall
of a mucinous cystadenoma. About 1% of the dermoids undergo malignant
transformation (e.g., thyroid carcinoma, melanoma, but most commonly, squamous
cell carcinoma).

Question 75

The karyotype of almost all benign
ovarian teratomas is ______________. From the results of chromosome banding techniques and the
distribution of electrophoretic variants of enzymes in normal and teratoma cells, it has been
suggested that the tumors arise from an ovum after the first meiotic division. [96] Other
derivations have also been proposed

Answer 75

46,XX

Question 76

The_______________ are a remarkable, rare group of tumors, the most common of which
are struma ovarii and carcinoid. They arealways unilateral,although a contralateral teratoma
may be present.

Answer 76

Monodermal or Specialized Teratomas.

Question 77

The specialized teratomas are a remarkable, rare group of tumors, the most common of which
are___________ and _________.

Answer 77

struma ovarii and carcinoid.

Question 78

______________ is composed entirely of mature thyroid tissue.

Interestingly, these
thyroidal neoplasms may hyperfunction, causing hyperthyroidism.

The ovarian carcinoid, which
presumably arises from intestinal epithelium in a teratoma, may also be functional, particularly
large (>7 cm) tumors, producing 5-hydroxytryptamineand the carcinoid syndrome.

Answer 78

Struma ovarii

Question 79

Primary
ovarian carcinoidcan be distinguished frommetastatic intestinal carcinoid, which is virtually
always bilateral. Even rarer is the strumal carcinoid, a combination of struma ovarii and
carcinoid in the same ovary. Only about 2% of carcinoids metastasize.

Question 80

These are rare tumors that differ from benign teratomas in that the component tissues
resemble embryonal and immature fetal tissue. The tumor is found chiefly in prepubertal adolescents and young women, the mean age being 18 years

Answer 80

Immature Malignant Teratomas.

Question 81

The tumors are bulky and have a smooth external surface. On section they
have a solid (or predominantly solid) structure. There are areas of necrosis and hemorrhage.
Hair, sebaceous material, cartilage, bone, and calcification may be present.

On microscopic
examination there are varying amounts of immature neuroepithelium, cartilage, bone, muscle,
and others.

An important risk for subsequent extra-ovarian spread is the histologic grade of
tumor (____________), which is based on the proportion of tissue containing immature
neuroepithelium

Answer 81

I through III

Question 82

The _______________ is best considered as the ovarian counterpart of the seminoma of the testis.
Similar to the seminoma, it is composed of large vesicular cells having a clear cytoplasm, welldefined
cell boundaries, and centrally placed regular nuclei.

Dysgerminomas account for about
2% of all ovarian cancers yet form about half of malignant germ cell tumors. They may occur in
childhood, but 75% occur in the second and third decades. Some occur in patients with gonadal
dysgenesis, including pseudohermaphroditism. Most of these tumors have no endocrine
function.

A few produce elevated levels of chorionic gonadotropin and may have syncytiotrophoblastic giant cells on histologic examination.

Answer 82

Dysgerminoma

Question 83

Like seminomas, dysgerminomas
express __________, _____________ and. [99] These transcription factors are implicated in maintenance
of pluripotency. They also express the receptor tyrosine kinase c-KIT. These proteins are
useful diagnostic markers and, in the case of c-KIT, may also serve as a therapeutic
target.

Answer 83

Oct3, Oct4, and Nanog

Question 84

Usually unilateral (80% to 90%), most are solid tumors ranging in size from
barely visible nodules to masses that virtually fill the entire abdomen. On cut surface they
have a yellow-white to gray-pink appearance and are often soft and fleshy.

On histologic
examination the dysgerminoma cells are dispersed in sheets or cords separated by scant
fibrous stroma (Fig. 22-46 ).As in the seminoma,thefibrous stroma is infiltrated with mature
lymphocytes and occasional granulomas. On occasion, small nodules of dysgerminoma are
encountered in the wall of an otherwise benign cystic teratoma; conversely, a predominantly
dysgerminomatous tumor may contain a small cystic teratoma.

Question 85

All _______________are malignant, but the degree of histologic atypia is variable, and only about
one third are aggressive. Thus, a unilateral tumor that has not broken through the capsule and
has not spread has an excellent prognosis (up to 96% cure rate) after simple salpingooophorectomy.
These neoplasms are responsive to chemotherapy, and even those that have
extended beyond the ovary can often be cured. [101] Overall survival exceeds 80%.

Answer 85

**dysgerminomas **

Question 86

This tumor is rare but is the second most common malignant tumor of germ cell origin. It is
thought to be derived from differentiation of malignant germ cells along the extra-embryonic
yolk sac lineage (see Fig. 22-42 ).

Similar to the normal yolk sac, the tumor is rich in α-
fetoprotein and α1-antitrypsin. Its characteristic histologic feature isa glomerulus-like structure
composed of a central blood vessel enveloped by germ cells within a space lined by germ cells
(Schiller-Duval body) ( Fig. 22-47 ).Conspicuous intracellular and extracellular hyaline droplets
are present in all tumors, and some of these stain for α-fetoprotein by immunoperoxidase
techniques.

Answer 86

Endodermal Sinus (Yolk Sac) Tumor

Question 87

More commonly of placental origin, the_______________, like the endodermal sinus tumor, is an
example of extra-embryonic differentiation of malignant germ cells.

It is generally held that a
germ cell origin can be confirmed only in the prepubertal girl, because after this age an origin
from an ovarian ectopic pregnancy cannot be excluded.

Answer 87

choriocarcinoma

Question 88

Granulosa cell tumors have clinical importance for two reasons:________________

Answer 88

(1) their potential to elaborate
large amounts of estrogen and

(2) the small but distinct hazard of malignancy in the granulosa
cell forms.

Question 89

Other Germ Cell Tumors
These include:

Answer 89

e (1) embryonal carcinoma, another highly malignant tumor of primitive embryonal
elements, histologically similar to tumors arising in the testes ( Chapter 21 ) [75] ;

(2)
polyembryoma, a malignant tumor containing so-called embryoid bodies; and

(3) mixed germ
cell tumors containing various combinations of dysgerminoma, teratoma, endodermal sinus
tumor, and choriocarcinoma

Question 90

These ovarian neoplasms are derived from the ovarian stroma, which in turn is derived from the
sex cords of the embryonic gonad.

Because the undifferentiated gonadal mesenchyme
eventually produces structures of specific cell type in both male (Sertoli and Leydig) and female
(granulosa and theca) gonads, tumors resembling all of these cell types can be identified in the
ovary. [102] Moreover, because some of these cells normally secrete estrogens (granulosa and
theca cells) or androgens (Leydig cells), their corresponding tumors may be either feminizing
(granulosa–theca cell tumors) or masculinizing (Leydig cell tumors).

Answer 90

SEX CORD–STROMAL TUMORS

Question 91

Granulosa–Theca Cell Tumors
This designation embraces ovarian neoplasms composed of varying proportions of granulosa
and theca cell differentiation. They may be composed almost entirely of granulosa cells or a
mixture of granulosa and theca cells. Collectively, these neoplasms account for about 5% of all
ovarian tumors. Although they may be discovered at any age, approximately two thirds occur in
postmenopausal women.

Question 92

Granulosa cell tumors are usually unilateral and vary from microscopic foci to
large, solid, and cystic encapsulated masses.

• *Tumors that are hormonally active** have a
• *_______________** to their cut surfaces, due to intracellular lipids.

The pure thecomas are solid,
firm tumors.
The granulosa cell component of these tumors takes one of many histologic patterns. The
small, cuboidal to polygonal cells may grow in anastomosing cords, sheets, or strands ( Fig.
22-48A ). In occasional cases small, distinctive, gland-like structures filled with an acidophilic
material recall immature follicles (Call-Exner bodies). When these structures are evident the
diagnosis is straightforward. The thecoma component consists of clusters or sheets of
cuboidal to polygonal cells. In some tumors, the granulosa or theca cells may appear plumper
and have ample cytoplasm characteristic of luteinization (i.e., luteinized granulosa–theca cell
tumors).
Ovarian Tumors
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Answer 92

yellow coloration

Question 93

The tumor cells are arranged in sheets
punctuated by small follicle-like structures

Answer 93

Call-Exner bodies

Question 94

_Functionally active tumors in young girls (juvenile granulosa cell tumors) may
produce precocious sexual development in prepubertal girls. In adult women they may be
associated with endometrial hyperplasia, cystic disease of the breast, and endometrial
carcinoma. About 10% to 15% of women with steroid-producing tumors eventually develop an
endometrial carcinoma. Occasionally, granulosa cell tumors produce androgens, masculinizing
the patient.

Question 95

All granulosa cell tumors are potentially malignant. It is difficult to predict their biologic behavior
from histology. [102] The estimates of malignancy (recurrence, extension) range from 5% to
25%. In general, malignant tumors pursue an indolent course in which local recurrences may be
amenable to surgical therapy. Recurrences within the pelvis and abdomen may appear 10 to 20
years after removal of the original tumor. The 10-year survival rate is approximately 85%.
Tumors composed predominantly of theca cells are almost never malignant.

Question 96

Fibromas of the ovary are unilateral in about 90% of cases and are usually solid, spherical or
slightly lobulated, encapsulated, hard, gray-white masses covered by glistening, intact ovarian
serosa ( Fig. 22-49B ). On histologic examination, they are composed of well-differentiated
fibroblasts and a scant interspersed collagenous connective tissue. Focal areas of thecal
differentiation may be identified.

Question 97

Most of these tumors are pure fibromas and are hormonally inactive.

These tumors usually
come to attention as a pelvic mass, sometimes accompanied by pain and through two other
curious associations.

The first is ascites, which is found in about 40% of cases in which the
tumors measure more than 6 cm in diameter. Uncommonly there is also a hydrothorax, usually
only of the right side. This combination of findings (i.e., ovarian tumor, hydrothorax, and
ascites) is designated Meigs syndrome. Its genesis is unknown. The second association is with

Question 98

Sertoli–Leydig Cell Tumors (Androblastomas)
These tumors recapitulate, to a certain extent, the cells of the testis at various stages of
development. [105] They commonly produce masculinization or at least defeminization, but a
few have estrogenic effects. They occur in women of all ages, although the peak incidence is in
the second and third decades. The embryogenesis of such male-directed stromal cells remains
a puzzle. These tumors are unilateral and may resemble granulosa–theca cell neoplasms.

Question 99

The cut surface is usually solid and varies from gray to golden brown in
appearance ( Fig. 22-50A ). On histologic examination the well-differentiated tumors show
tubules composed of Sertoli cells or Leydig cells interspersed with stroma ( Fig. 22-50B ). The
intermediate forms show only outlines of immature tubules and large eosinophilic Leydig cells.
The poorly differentiated tumors have a sarcomatous pattern with a disorderly disposition of
epithelial cell cords. Leydig cells may be absent. Heterologous elements, such as mucinous
glands, bone, and cartilage, may be present in some tumors.

Question 100

The ovarian hilum normally contains clusters of polygonal cells arranged around vessels (hilar
cells). ____________ (pure Leydig cell tumors) are derived from these cells and are rare,
unilateral, and characterized histologically by large lipid-laden cells with distinct borders. A
typical cytoplasmic structure characteristic of Leydig cells (Reinke crystalloids) is usually
present. Women with hilus cell tumors usually present with evidence of masculinization,
hirsutism, voice changes, and clitoral enlargement. The tumors are unilateral. The most
Ovarian Tumors
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Answer 100

Hilus cell tumors

Question 101

_______________is an uncommon tumor thought to be composed of germ cells and sex cord
–stroma derivatives. It occurs in individuals with abnormal sexual development and in gonads of
indeterminate nature.

Eighty percent of patients are phenotypic females, and 20% are
phenotypic males with undescended testicles and female internal secondary organs. On
microscopic examination the tumor consists of a mixture of germ cells and sex cord derivatives
resembling immature Sertoli and granulosa cells arranged in nests. A coexistent dysgerminoma
occurs in 50% of the cases. The prognosis is excellent if the tumor is completely excised.

Answer 101

Gonadoblastoma

Question 102

The most common metastatic tumors of the ovary are derived from tumors of _____________
the uterus, fallopian tube, contralateral ovary, or pelvic peritoneum.

Answer 102

müllerian origin:

Question 103

The most common extramüllerian
tumors metastatic to the ovary are________________________________________

. Also included in this group are the rare
cases of pseudomyxoma peritonei, derived from appendiceal tumors.

Answer 103

carcinomas of the breast and gastrointestinal tract,
including colon, stomach, biliary tract, and pancreas

Question 104

A classic example of
metastatic gastrointestinal neoplasia to the ovaries is termed _______________ characterized
by bilateral metastases composed of mucin-producing, signet-ring cancer cells, most often of
gastric origin.

Answer 104

Krukenberg tumor,