Female Genital Tract of the OVARY Flashcards
(105 cards)
1
Q
The most common types of lesions encountered in the ovary include_________________.
I
A
functional or benign cysts
and tumor
2
Q
__________________ovary (oophoritis) are uncommon, and usually accompany tubal inflammation.
A
Intrinsic inflammations
3
Q
Rarely, a__________________ involving ovarian
follicles (autoimmune oophoritis) occurs and is associated with **infertility. **
A
** primary inflammatory disorder**
4
Q
The ovary has three
main histologic compartments:
Note: Each compartment gives rise to distinct non-neoplastic and
neoplastic entities, as discussed below.
A
(1) the surface müllerian epithelium,
(2) the germ cells, and
3) the sex cord–stromal cells.
5
Q
Non-Neoplastic and Functional Cysts
A
FOLLICLE AND LUTEAL CYSTS
POLYCYSTIC OVARIES AND STROMAL HYPERTHECOSIS
6
Q
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**
A
Cystic follicles
7
Q
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.
A
cystic follicle
8
Q
_________________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.
A
Granulosa luteal cysts (corpora lutea)
9
Q
____________________ 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
A
Polycystic ovarian disease (PCOD; formerly termed SteinLeventhal syndrome)
10
Q
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
A
Polycystic ovarian disease
11
Q
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.
A
GET THE PIC
12
Q
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.
A
13
Q
_______________, 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.
A
Stromal hyperthecosis, also called cortical stromal hyperplasia,
14
Q
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
A
theca lutein hyperplasia of
pregnancy
15
Q
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.
A
Ovarian Tumors
16
Q
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:
A
(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.
17
Q
There is also a group of tumors that defy
classification, and finally there are __________________
A
secondary or metastatic tumors to the ovary.
18
Q
TABLE 22-5 – WHO Classification of Ovarian Neoplasms
A
- SURFACE EPITHELIAL-STROMAL TUMORS
- SEX CORD–STROMAL TUMORS
- GERM CELL TUMORS
- MALIGNANT, NOT OTHERWISE SPECIFIED
METASTATIC CANCER FROM NONOVARIAN PRIMARY
19
Q
SURFACE EPITHELIAL-STROMAL TUMORS
A
- Serous tumors
- Mucinous tumors, endocervical-like and intestinal
type - Endometrioid tumors
- Clear cell tumors
- Transitional cell tumors
- Epithelial-stromal
20
Q
Serous tumors
A
- Benign (cystadenoma)
- Borderline tumors (serous borderline
tumor)
- Malignant (serous adenocarcinoma)
21
Q
Mucinous tumors, endocervical-like and intestinal
type
A
- Benign (cystadenoma)
- Borderline tumors (mucinous borderline
tumor)
- Malignant (mucinous adenocarcinoma)
22
Q
Endometrioid tumors
A
Benign (cystadenoma)
Borderline tumors (endometrioid borderline
tumor)
Malignant (endometrioid adenocarcinoma)
23
Q
Clear cell tumors
A
Benign
Borderline tumors
Malignant (clear cell
adenocarcinoma)
24
Q
Transitional cell tumors
A
- Brenner tumor
- Brenner tumor of borderline malignancy
- Malignant Brenner tumor
- Transitional cell carcinoma (non-Brenner
type)
25
Epithelial-stromal
Adenosarcoma
Malignant mixed müllerian
tumor
26
SEX CORD–STROMAL TUMORS
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
27
GERM CELL TUMORS
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
28
METASTATIC CANCER FROM NONOVARIAN PRIMARY
Colonic,
appendiceal
Gastric
Breast
Ovarian Tumors
29
Although some of the specific tumors have distinctive features and are hormonally active, **most
are nonfunctional**and**tend 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 c**ompression 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.
bilateral
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
TUMORS OF SURFACE (MÜLLERIAN) EPITHELIUM
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)**.
serous, mucinous, and endometrioid tumors
32
The **benign tumors** are often further classified based on the
components of the tumors, which may include\_\_\_\_\_\_\_\_\_\_\_\_\_ ,\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ and \_\_\_\_\_\_\_\_\_\_\_\_
1. cystic areas **(cystadenomas),**
2. cystic and fibrous areas **(cystadenofibromas**), and
3. predominantly fibrous areas **(adenofibromas)**
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.
cystadenocarcinomas
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),**
e**ndometrioid (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
transformation of coelomic epithelium
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:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
.
(1) those that arise in association with borderline tumors, and
(2) those that arise
as “de novo” carcinomas
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.
** borderline tumors**
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.**
Serous Tumors
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.
Serous carcinomas
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.
nulliparity, family history, and heritable mutations
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.
```
(1) low-grade (welldifferentiated)
carcinoma and (2) high-grade (moderately to poorly differentiated) carcinoma.
```
41
Molecular studies of **low- and high-grade serous carcinoma** have revealed d**istinct molecular**
genetic changes in the two types of carcinoma. [82]
The **low-grade tumors arising in serous
borderline tumors**have mutations in the\_\_\_\_\_\_\_\_\_\_\_\_\_\_, with**only rare mutations in
p53**
KRAS or BRAF oncogenes
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.**
**p53 gene**
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.
primary peritoneal serous carcinomas
44
The characteristic serous tumor may present on **gross examination** as either a
**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** ( Fig. 22-37A ), \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
* *cystic lesion in which the papillary epithelium** is contained within a** few fibrous walled cysts**
* *(intracystic)** or projecting from the** ovarian surface.**
45
**Benign tumors typically**
present with a\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
smooth glistening cyst wall with no epithelial thickening or with small papillary
projections
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 approximately**66% 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 ).
increased number of papillary projections
47
On histologic examination, the cysts
are**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ in benign tumors** ( Fig. 22-38A ).
**Microscopic papillae** may be found.
** lined by columnar epithelium, which has abundant cilia**
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 ).
** 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**
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**, includin**g pleomorphism**,**atypical mitotic figures, and multinucleation.**
1. **Larger amounts of solid or papillary tumor mass, **
2. **irregularity in the tumor mass,**
3. **and fixation or nodularity of the capsule **
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\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
1. stromal papillae with a columnar epithelium
2. increased architectural complexity and epithelial cell stratification.
3. “micropapillary” serous carcinoma
4. invasion of underlying stroma.
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
occur**on the**surface 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.
**unencapsulated
serous tumors**
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,**and**patients may survive for relatively**
**long periods before dying of disease**.
Borderline serous tumors
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 mass**is, respectively,**100% and 70%,**whereas the**5-year survival rate for the same
tumors involving the peritoneum**is about**90% and 25%,** respectively. Because of their
protracted course, **borderline tumors may recur after many years, and 5-year survival is not
synonymous with cure.**
**high-grade tumors**
**" **so mas mataas and 5 yr survival rate kapag confined lng sa ovary
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 carcinomas**are relatively u**ncommon and account for fewer than 5% of all
ovarian cancers.**
Mucinous tumors
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**.
including smoking, which is not
a risk factor for serous ovarian tumors
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 alteratio**n that has been identified is **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**
**mutation of the KRAS proto-oncogene.**
**Note : ****Mutations in KRAS**are common in**benign 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.
57
1. In gross appearance, the **mucinous tumor**s differ from the serous variety in
**several ways**. They are characterized by \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_l. Only **5%** of primary mucinous cystadenomas and mucinous cystadenocarcinomas
are **bilatera**l.
2. Mucinous tumors tend to\_\_\_\_\_\_\_\_\_\_\_\_\_\_ They appear grossly as **multiloculated tumors filled**
with s**ticky, gelatinous fluid rich in glycoproteins** ( Fig. 22-39A ).
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.
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.
lining of tall, columnar epithelial cells with
apical mucin and the absence of cilia, **akin to benign cervical or intestinal epithelia**
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\_\_\_\_\_\_\_\_\_\_\_\_\_**
** **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.
60
A clinical condition referred to as \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_is defined by **extensive mucinous
ascites, cystic epithelial implants**on the**peritoneal surfaces,****adhesions,** and frequently
**mucinous tumor involving the ovaries** ( Fig. 22-40 ).
pseudomyxoma peritonei
61
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are uncommon. However, endometrioid carcinomas account for approximately **20% of
all ovarian cancers.**
Benign endometrioid tumors, called **endometrioid adenofibromas**, and **borderline endometrioid**
**tumors**
62
Endometrioid tumors are distinguished from serous and mucinous tumors
by the ______________ bearing a c**lose resemblance to benign or malignant
endometrium**.
presence of tubular glands
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 the**relatively good prognosis** in such cases suggests
that the two may arise independently rather than by metastatic spread from one another.
endometriosis
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
endometriosis**are usually about a**decade younger than women with endometrioid carcinoma**
that is not associated with endometriosis. Molecular studies have found relatively **frequent
mutations in the PTEN tumor suppressor gene**and in the**KRAS and β-catenin oncogenes**, as
well as microsatellite instability. [90] Similar to endometrioid carcinomas of the endometrium,
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%.
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 of**müllerian 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.
Clear Cell Adenocarcinoma
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.
Cystadenofibromas
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 contain**microcysts or glandular spaces**lined by**columnar, mucin-secreting
cells.**
Brenner tumors
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 trac**t, 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, b**ut borderline (proliferative
Brenner tumor) and malignant counterparts have been reported.**
Brenner tumors
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 r**emarkable similarity to germ cell tumors in the male testis (** Chapter 21 )
* *and arise in a similar manner (** Fig. 22-42 ).
Germ cell tumors
71
Teratomas
Teratomas are divided into three categories
: (1) mature (benign),
(2) immature (malignant), and
(3) monodermal or highly specialized.
72
Most benign teratomas are **cystic and are better known** in **clinical parlance as dermoid cysts.
Cystic teratomas**are usually found in young women during the**active 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.
Mature (Benign) Teratomas.
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.**
**Benign teratomas**
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).**
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
46,XX
76
The\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are a remarkable, rare group of tumors, the **most common of which
are struma ovarii and carcinoid**. They are**always unilateral**,**although a contralateral teratoma**
**may be present.**
Monodermal or Specialized Teratomas.
77
The specialized teratomas are a remarkable, rare group of tumors, the most common of which
are\_\_\_\_\_\_\_\_\_\_\_ and \_\_\_\_\_\_\_\_\_.
struma ovarii and carcinoid.
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-hydroxytryptamine**and the carcinoid syndrome.
Struma ovarii
79
**Primary
ovarian carcinoid**can be distinguished from**metastatic 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.
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
Immature Malignant Teratomas.
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
**I through III**
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**.
Dysgerminoma
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.
Oct3, Oct4, and Nanog
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,**the**fibrous 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.
85
**All \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_are malignant,** but the degree of histologic atypia is variable, and only about
one third are aggressive. Thus, a u**nilateral 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%.
**dysgerminomas **
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 is**a 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.
Endodermal Sinus (Yolk Sac) Tumor
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.
choriocarcinoma
88
Granulosa cell tumors have clinical importance for two reasons:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
(1) their potential to elaborate
large amounts of estrogen and
(2) the small but distinct hazard of malignancy in the granulosa
cell forms.
89
Other Germ Cell Tumors
These include:
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
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).
SEX CORD–STROMAL TUMORS
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.
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
2027
**yellow coloration**
93
The tumor cells are arranged in sheets
punctuated by **small follicle-like structures**
Call-Exner bodies
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.
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.
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.
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
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.
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.
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
2030
Hilus cell tumors
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.
Gonadoblastoma
102
The **most common metastatic tumors** of the ovary are derived from **tumors of \_\_\_\_\_\_\_\_\_\_\_\_\_**
the **uterus, fallopian tube, contralateral ovary, or pelvic peritoneum**.
**müllerian origin:**
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.**
carcinomas of the breast and gastrointestinal tract,
including colon, stomach, biliary tract, and pancreas
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.
Krukenberg tumor,
105
