lect 3- overy cancer

Ovarian Cysts and Tumors

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Ovaries

• The most important medical problems in ovaries are the neoplasms

• Death from ovarian cancers is more than that of cervix and uterus together

• Silent growth of ovarian tumors is the rule ,which make them so dangerous

Types of Ovarian Tumors• Functional

• Follicle cyst• Corpus luteum cyst• Theca lutein cyst

• Inflammatory• Tubo-ovarian abscess

• Benign tumors/cysts*• Endometriotic cyst• Brenner tumor• Benign teratoma (dermoid

cyst)• Fibroma*Rare or very rare potential

for malignancy

• Malignant (or malignant potential)• Malignant teratoma• Endometrioid carcinoma• Dygerminoma• Secondary ovarian tumor• Cystadenoma,

cystadenocarcinoma (>50% for serous, ~5% for mucinous)

• Granulosa cell tumor (15-20%)

• Arrhenoblastoma (<20%)• Theca cell tumor (<1%)

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Primarily Cystic Primarily Solid Mixed

•Mucinous cystadenoma (benign, sometimes grow quite large)•Serous cystadenoma (benign)•Adenocarcinoma (malignant)

•Fibroma (benign)•Brenner tumor (usually benign)•Granulosa Cell tumor (malignant, produces estrogen)•Thecoma (benign, produces estrogen, occasionally androgens)•Sertoli-Leydig Cell tumors (Generally benign, may produce androgens and/or estrogen)•Dysgerminoma (malignant, but usually good prognosis)

•Dermoid (teratoma, usually benign, may produce thyroid hormone)•Clear cell carcinoma (usually malignant)•Adneocarcinoma (malignant)•Endometrioid Carcinoma (malignant)

Ovarian neoplasms may be primarily cystic, solid, or mixed. Some are benign, some are malignant. Some produce enough hormone to cause symptoms for the patient. Some examples of these shown below.

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Ovarian Cysts and Tumors

• Non neoplastic cysts are common but they are not serious problems

• Primary inflammation of ovaries is rare• Salpingitis of fallopian tubes frequently causes

periovarian reaction (salpingo-Oophoritis).

• Frequently ,the ovaries affected by endometriosis is a form of an ovarian cyst that results from ectopic endometrial tissue being present in the ovary.

• During the normal cyclic hormonal changes, As the blood is trapped within the ovarian capsule or stroma, it gradually accumulates, forming a chronic hematoma, known as an endometrioma.

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Non-Neoplastic and Functional Cysts of ovary

• Follicular and Luteal cysts are most probably physiologic

• Cystic Follicles: Innocent lesions originate from unruptured follicles or in follicles that have ruptured and sealed.

• Usually they are small 1 – 1.5 cm ,and filled by clear fluid

Ovarian Cysts

• Signs & Symptoms– Pressure, backache, menstrual irregularities,

pain, breast atrophy, sterility, & hirsutism

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Follicular Cyst

• Is due to distention of unruptured graafian follicle

• It is sometimes associated with hyperestrinism and endometrial hyperplasia.

• Corpus luteum cyst

• It results from hemorrhage into a persistent mature corpus luteum.

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Theca lutein cyst

• Results from gonadotropin stimulation.

• Often multiple and bilateral.

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Ovarian Cancer 16

• Definition• Ovarian tumors may arise at any age, but are

commonest between 30 and 60. • 1.Ovarian tumors are particularly liable to be

or to become malignant.• 2.In their early stages they are asymptomatic

and painless.• 3.They may grow to a large size and tend to

undergo mechanical complications such as torsion and perforation.

OVARIAN TUMOURS

Ovarian Cancer: Burden of suffering

• Fifth leading cause of cancer death in women (after lung, breast and colon)

• Overall 5-year survival rate is 35%• The “silent killer”: asymptomatic in early stages• 75% diagnosed with advanced stage disease;

5-year survival only 10-28%• Woman’s lifetime risk of dying from ovarian

cancer is 1.1%

Risk Factors

• Most women with ovarian cancer do not have any known risk factors

• However, there are several factors that may increase risk of ovarian cancer

• Having one or more of these risk factors doesn’t mean that ovarian cancer will develop, but the risk may be higher compared to the average woman

Risk Factors

• Inherited genetic mutations – Often exhibited by a family or personal history of

breast, colorectal or ovarian cancer

• Family history of ovarian cancer• Age• Reproductive history and infertility• Hormone replacement therapy• Obesity

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Ovarian Tumors classification

• Diversity of pathologic entities because of the three cell types make up the normal ovary

• Three cell types :

• 1- the surface epithelium tumors

• 2- Germ cells tumors

• 3- Stromal /sex cord cells tumors

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Ovarian Tumors

Epithelial tumors: These tumors arise from a layer of cells that surrounds the outside of the ovary called the germinal epithelium.

• About 70-80% of all ovarian cancers are epithelial. • These are most common in women who have been

through menopause (aged 45-70 years).

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Ovarian Tumors

Stromal tumors: Stromal tumors develop from connective-tissue cells that help form the structure of the ovary and produce hormones.

• These account for 5-10% of ovarian cancers and also these tumors typically occur in women aged 40-60 years.

Germ cell tumors: Tumors that arise from germ cells (cells that produce the egg) account for about 15% of all ovarian cancers.

• These tumors develop most often in young women (including teenaged girls). Although 90% of women with this type of cancer are successfully treated, many become permanently infertile.

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Pathophysiology

Ovarian carcinoma can spread by local extension, lymphatic invasion, intraperitoneal implantation, hematogenous dissemination, and transdiaphragmatic passage.

Intraperitoneal dissemination is the most common and recognized characteristic of ovarian cancer.

Malignant cells can implant anywhere in the peritoneal cavity but are more likely to implant in sites of stasis along the peritoneal fluid circulation.

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Designation DefinitionStage I Cancer limited to the ovaries

IA Growth limited to one ovary, capsule intact, no malignant ascites, no tumor on external surface

IB Growth limited to both ovaries, capsule intact, no malignant ascites, no tumor on external surface

IC As for IA or IB but with surface growth, ruptured capsule (before or during surgery), positive washings, or malignant ascites

Stage II Growth involving one or both ovaries with pelvic extension

IIA Extension and/or metastases to the uterus and/or tubes

IIB Extension to other pelvic organsIIC As for IIA or IIB but with surface growth, ruptured capsule (before or during

surgery), positive washings, or malignant ascites

Stage III Tumor involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes; liver capsule involvement

IIIA Tumor grossly limited to the true pelvis with negative nodes but microscopic seeding of abdominal peritoneal surfaces

IIIB Abdominal peritoneal implants, but none exceeding 2 cm; nodes negative

IIIC Abdominal peritoneal implants larger than 2 cm and/or positive retroperitoneal or inguinal nodes

Stage IV Tumor involving one or both ovaries with distant metastases; pleural effusions must be demonstrated to harbor malignant cells; liver parenchymal involvement

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Classification of Ovarian Tumors, Surface Epithelial Tumors

-Serous Tumors : Benign ,Borderline and malignant

-Mucinous T. : Benign ,Borderline , and malignant

-Endometrioid T. : Benign, Borderline, and malignant

Clear cell papillary serous

-Transitional cell T. :Brenner tumors, Benign ,Borderline ,and malignant

-Undifferentiated Carcinoma

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l-Epithelial Ovarian Cancer

• 65 – 70 % of overall tumors

• 90 % of malignant tumors

• Age 20+

• Traditionally divided into Benign ,Malignant ,and Borderline in malignancy

• Can be strictly epithelial (serous ,Mucinous)

• Only 25% diagnosed in Stage I

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A. Serous Tumors

• The most frequent ovarian tumor

• Age is 30 -40

• May be solid ,usually cystic

• Cystadenoma or Cystadenofibroma

• 65% benign ,15% low malignant potential , and 25% malignant

• 65 % of all ovarian cancers

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Serous Tumors

• Most are large ,spherical to ovoid ,cystic structures

• 5 – 10 cm and might be 30-40 cm

• 25% of benign tumors are bilateral

• The surface of the benign is smooth and glistening .

• In contrast to the malignant forms ,the surface is nodular and irregular

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Serous Tumors

• Cystic spaces are filled by serous fluide• Papillary formation is very important and need to

be sampled well• Histologically the benign tumors are lined by a

single layer of tall columnar epithelium• Papillary formation can be seen in both the

benign and the malignant ones

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Serous Tumors

Psammoma bodies could be seenBetween the clearly benign and the solid

malignant tumors we can see the tumors of low malignant potential

The tumors may seed the peritoneum, the implants of tumors are non invasive.

Sometimes may behave as invasive peritoneal implants

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Psammoma bodies

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Figure 22-39 A, Borderline serous cystadenoma opened to display a cyst cavity lined by delicate papillary tumor growths. B, Cystadenocarcinoma. The cyst is

opened to reveal a large, bulky tumor mass.

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Figure 22-40 Papillary serous cystadenoma revealing stromal papillae with a columnar epithelium.

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Figure 22-42 Papillary serous cystadenocarcinoma of the ovary with invasion of underlying stroma.

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Mucinous Tumors

• Epithelium is consists of mucin-producing cells

• Less likely to be malignant

• 10% of ovarian cancers

• 80% of them benign

• 10% LMP

• 10% malignant

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Figure 22-44 A, A mucinous cystadenoma with its multicystic appearance and delicate septa. Note the presence of glistening mucin within the cysts.

B, Columnar cell lining of mucinous cystadenoma.Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 April 2008 01:14 PM)

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Brenner Tumor• Transitional cell epithelium

• Most are benign

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Figure 22-46 A, Brenner tumor (right) associated with a benign cystic teratoma (left). B, Histologic detail of characteristic epithelial

nests within the ovarian stroma. (Courtesy of Dr. M. Nucci, Brigham and Women's Hospital, Boston, MA.)

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Papillary adenocarcinoma, ovary

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Sex Cord Tumors• 1. Granulosa cell tumor (granulose-theca cell tumor)• 2. Thecoma (theca cell tumor)• 3. Interstitial cell tumor (luteoma, lipid cell tumor,

steroid cell tumor)• 1- Granulosa cell tumor • Most postmenopausal ,could be any age• Unilateral• Solid and cystic • Tiny to large in size• Produce estrogen• Malignant behaviour in 5-25%

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Sex Cord Tumors,Thecoma-Fibroma

• Any age

• Unilateral

• Solid gray to yellow

• Rarely malignant

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Granulosa – theca cell tumor.

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Sex Cord TumorsSertoli - Leydig

• All ages

• Unilateral Gray to yellow

• Produce androgens

• Uncommonly malignant

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 Sex cord tumor with annular tubules.

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Germ Cell Tumors

A germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads (ovary and testis).

- -Dysgerminoma

- -Yolk Sac Tumor- -Embryonal Carcinoma- -Choriocarcinoma- -Teratoma : Mature, Immature- -Polyembryoma- primary choriocarcinoma

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Germ Cell TumorsDysgerminoma

• 2nd and 3rd decades

• Unilateral

• Counterpart to Seminoma in male

• Solid ,gray to yellow

• All malignant

• PLAP positive

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Embryonal carcinoma

• 2nd and 3rd decade

• Solid

• Aggressive

• CD 30 positive.

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Germ Cell TumorsTeratoma

• 15-20 % of Ovarian tumors• Majority in the first 2 decades• The younger the patient ,the greater the

likelihood of malignancy• Over 90% are benign cystic ,mature

teratomas• Immature teratomas are malignant and

are rare.

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Figure 22-48 Opened mature cystic teratoma (dermoid cyst) of the ovary. Hair (bottom) and a mixture of tissues

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Endodermal Sinus (Yolk Sac) Tumor

• 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)

• Most patients are children or young women presenting with abdominal pain and a rapidly developing pelvic mass.

• The tumors usually appear to involve a single ovary but grow rapidly and aggressively.

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Figure 22-52 A Schiller-Duval body in yolk sac carcinoma.

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Choriocarcinoma

• More commonly of placental origin, the choriocarcinoma, similar to the

• Most ovarian choriocarcinomas exist in combination with other germ cell tumors, and pure choriocarcinomas are extremely rare.

• are aggressive tumors that generally have metastasized widely through the bloodstream to the lungs, liver, bone, and other viscera by the time of diagnosis.

• high levels of chorionic gonadotropins that are sometimes helpful in establishing the diagnosis or detecting recurrences.

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Ovarian TumorsMetastatic Carcinoma

• Older ages

• Mostly Bilateral

• Primaries are Breast ,lung, and G.I.T. (Krukenberg Tumors)

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Symptoms• Digestive symptoms, such as gas, indigestion,

constipation, or a feeling of fullness after a light meal• Bloating, distention or cramping• Abdominal or low-back discomfort• Pelvic pressure or frequent urination• Unexplained changes in bowel habits• Nausea or vomiting• Pain or swelling in the abdomen• Loss of appetite• Fatigue• Unexplained weight gain or loss• Pain during intercourse• Vaginal bleeding in post-menopausal women

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Diagnostic tools

• History• Pelvic Exam (including rectal)• Transvaginal Ultrasound – detection of

masses and mass characteristics• Tumor markers – CA-125, LPA (plasma

lysophosphatidic acid)• CT – assess spread to LN, pelvic and

abdominal structures• MRI – best for distinguishing malignant from

benign tumors

Treatment

• Depends on staging, tumor type, age, desire for future fertility

• Can include surgery, chemotherapy and/or radiation therapy

• Clinical trials are ongoing

Surgical treatment

• Primary debulking and cytoreduction; may include:– Bilateral salpingo-oopherectomy– Hysterectomy– Lymphadenectomy (para-aortic, inguinal)– Omentectomy– “brushing” of diaphragm, examination of liver

Chemotherapy and Radiation

• Usually 6 cycles of chemotherapy

• Cisplatin (or Carboplatin) plus Paclitaxel most commonly used combination therapy

• XRT