PATH: Ovary & Fallopian Tube

Usually from the GI tract

A KRUKENBURG tumor in the ovary is depicted above. Where do krukenburg tumors typically mestastasize from?

CHLAMYDIA AND GONORRHEA

Acute supparative salpingitis (PID) often affects the fallopian tubes. What diseases are known to cause PID?

Metastasis from colon carcinoma

All metastases from GI tract are not going to be of signet ring type What type of mets is shown above? Cells stratified, dark nuclei, high N/C ratio

5. 46xxx, should be just 46xx

All of the following are potential causes of teratomas except? 1. Witches 2. Nightmares 3. Adultery with the devil 4. Tend to rise from ovum after first meiotic division 5. 46xxx

ENDOMETRIOID has genetic associations to PTEN, KRAS, and p53, while in CLEAR CELL, histologically you will see large tumor CLEAR CELLS with hobnail cytoplasm with the nucleus pushed over to one side.

Both ENDOMETRIOID and CLEAR CELL surface epithelial tumors have an association with endometriosis and endometrioid carcinoma, how would you differentiate the two?

IMMATURE MALIGNANT TERATOMA

Brain and neuronal tissue (as seen here) is often classically associated with what germ cell tumor of the ovary?

1) STRUMA OVARII- composed of THYROID tissue and associated with hypERthyroidism 2) CARCINOID - arises from intestinal epithelium and may produce carcinoid syndrome 3) STRUMAL CARCINOID - mixture of struma and carcinoid

Describe the 3 subcategories of monodermal teratomas.

These are usually *unilateral, solid, lobulated, hard, gray white and covered by intact serosa* FIBROMAS: composed of fibroblasts (makes the tumor hard); NONHORMONAL THECOMAS: plump spindle cells with lipid droplets; thecomas may secrete estrogen - (thecoma component may be hormonally active)

Describe the general make up of a fibroma-thecoma tumor.

BENIGN: smooth glistening cyst wall with NO epithelial thickening or papillary projections. Lined by columnar cells with cilia. BORDERLINE: increased # of papillary projections with complex stroma. Mild nuclear atypia, but NO infiltrative growth into the stroma MALIGNANT: large amounts of solid or papillary masses, irregularity, nodularity, MARKED NUCLEAR ATYPIA, pleomorphism, mitotic figures and multinucleation

Describe the morphologic changes you would see as a serous tumor progresses from benign -> borderline -> malignant.

DYSGERMINOMA germ cell tumor

Elevated levels of CHORIONIC GONADOTROPIN is a key finding in what germ cell tumor of the ovary? Hint: grossly appears as a solid, soft, fleshy yellow white mass with lymphocytic infiltrate.

FOXL2 which encodes a transcription factor.

Granulosa-Theca cell tumors are associated with what gene mutation?

GRANULOSA CELL TUMOR

Grooved "coffee bean" nuclei with sheets of cells with multiple Call-Exner bodies with positive inhibin antibody is classic histological finding of what ovarian tumor?

ENDODERMAL SINUS TUMOR

High levels of ALPHA Feta Protein (AFP) and Alpha1Antitrypsin are classic findings in what germ cell tumor?

A borderline tumor will have more papillary growth and nuclear atypia, while a cystadenocarcinoma will have more SOLID GROWTH pattern with obvious nuclear atypia and stratification, may also have STROMA INVASION.

How can you differentiate a mucinous cystadenoma from a mucinous cystadenocarcinoma?

Infections in the fallopian tube can lead to obstruction and disruption of transport of the egg and/or sperm-> infertility *inflammation inhibits movement of egg through fallopian tube and predispose to abnormal implantation*

How does PID result in infertility?

Expression of *OCT-3, OCT-4, NANOG transcription factors and expression of the receptor tyrosine kinase KIT

In Dysgerminoma, elevated levels of chorioninc gonadotropin can help make the diagnosis. Most of these tumors occur in the 2nd and 3rd decade of life. What are the genetic factors associated with dysgerminoma?

BURKIT'S LYMPHOMA

In this picture, you can see a proliferation of lymphocytes → 'starry-sky appearance a. Black = lymphocytes b. Clear stars = macrophages What is the pathology classically associated with starry sky appearance?

DYSGERMINOMA

LYMPHOCYTIC infiltrate and well defined borders with large vesicular cells and clear cytoplasm are characteristic features of which germ cell tumor of the ovary?

FIBROMA-THECOMA SEx cord stromal tumor

MEIG's syndrome consists of ovarian tumors, hydrothorax/pleural effusion and ascites. What ovarian tumor is MEIG's syndrome classically associated with?

GLYCOPROTEINS

Mucinous tumors are typically LARGE cystic masses, multiloculated and filled with gelatinous fluid rich in ______________.

ENDOMETRIOID SURFACE EPITHELIAL TUMOR May resemble endometrial adenocarcinoma

PTEN, KRAS, and p53 mutations, well differentiated tumors and an associated to endometriosis are characteristics of what type of ovarian neoplasm? What cancer may this resemble?

Between ages 20-45

SEROUS surface epithelial tumors can be benign, borderline or malignant. At what ages would you expect to see benign or borderline malignant lesion?

PEUTZ-JEGHERS SYNDROME

Sex Cord Tumor with annular tubules and eosinophilic hyaline bodies are classically associated with what GI pathology?

CLEAR CELL Surface Epithelial Tumor

Solid tumors with cells arranged in sheets or tubules. Large tumor cells of this neoplasm wil have hobnail cytoplasm and may be associated with endometriosis or endometrioid carcinoma.

FALSE - malignancy risk increases with age

T/F As a woman ages, she is less at risk for malignant ovarian cancer because she has stopped ovulating.

FALSE- there is NO significant serum screening tool available, CA-125 is sensitive but NOT specific because can be elevated in ANY peritoneal irritation

T/F CA-125 is a sensitive and specific marker for ovarian surface epithelial tumors.

FALSE - this IS AN AGGRESSIVE LESION

T/F Endodermal sinus tumors classically presents in children and young women as abdominal pain and a rapidly growing mass. Overall, these are not aggressive lesions though.

FALSE - usually FATAL

T/F Mucinous cancers that have spread beyond the ovary are usually not fatal.

FALSE- only thecomas have lipid droplets that you can stain for

T/F thecomas and fibromas both contain lipid droplets.

STRUMAL CARCINOID MONODERMAL TERATOMA germ cell tumor

The above picture is a pathology that arises from intestinal epithelium and thyroid tissue. You can see nests of cells with minimal cytoplasm. What is the pathology?

STRUMA OVARII Germ cell teratoma

The above picture is composed of thyroid tissue, often associated with hyperthyroidism.

1) Tests - Chorionic gonadotropin assay and Ultrasound (can't always see it) 2) Treatment - Surgery (often need to do exploratory surgery); Biopsy of site to identify fetal elements or villi

The clinical course of an ectopic pregnancy is: 1. Severe abdominal pain occurring approx. six weeks after a menstrual period (take history) 2. Signs of an acute abdomen (rigidity, rebound tenderness, guarding) What tests should you order? What's the best tx option?

OVARIAN TORSION

The ovaries are moveable structures that can turn and twist on itself. When this happens, the ovary enlarges and can mimic cystic disease and or tumors. What is this pathology called?

MATURE TERATOMA

This germ cell tumor is often referred to as a dermoid cyst, is derived from totipotent cells and is commonly seen in women of reproductive age. The tissue resembles that seen in an adult, will see hair, squamous cells bone, cartilage, and potentially thyroid tissue.

SEROUS CYSTADENOMA

This is a benign neoplasm of the ovary with stromal papillae and non atypic columnar epithelia. What is the name of this lesion?

PSEUDOMYXOMA PERITONEI Associated with MUCINOUS surface epithelial tumors of the ovary.

This is a clinical condition marked by extensive mucinous ascites, cystic epithelial implants on the peritoneal surfaces, adhesions, and frequent involvement of the ovaries. What is the name of this massive overgrowth and what malignant ovarian neoplasm is it associated with?

HIGH GRADE SEROUS CARCINOMA

This is a high grade malignant lesion with very complex architecture, increased stratification of epithelial cells and invasion of underlying stroma. Often associated with p53 mutation, BRCA1 or BRCA2 mutation. What is this pathology?

ENDODERMAL SINUS TUMOR

This is a rare tumor, but is the 2nd most common malignant tumor of germ cell origin.

SMALL CELL CARCINOMA

This metastasis came from the lung and you can see very minimal cytoplasm, small dense nuclei, not easily distinguishable cell borders. What type of cancer is this?

POLYCYSTIC OVARIAN SYNDROM (PCOS)

This pathology is also known as STEIN LEVENTHAL SYNDROME, affects 3-6% women in reproductive age. While the etiology is poorly understood, this syndrome presents as numerous follicular cysts often associated with oligomenorrhea. What is the pathology?

TURNER'S SYNDROME

This pathology is associated with 45 X abnormality and presents as short stature. Individuals with this pathology are predisposed to coarctation of the aorta and classically associated with ovarian abnormalities: STREAK OVARIES that can lead to infertility and amenorrhea. What is the pathology?

TERATOMA

This picture represents a conglomeration of tissues, but whats key in this picture are the sebaceous glands. What is the name of this pathology?

BORDERLINE SEROUS TUMOR

This picture represents a neoplastic lesion of the ovary with increased architectural complexity and epitelial cell stratification and scattered nuclei. Often associated with KRAS or BRAF mutation. What is the name of this lesion?

DYSGERMINOMA germ cell tumor

This solid, yet soft yellow white mass usually presents only unilaterally with an overall good survival. Gene mutations: OCT-3, OCT-4, NANOG and KIT.

CHORIOCARCINOMA

This tumor is distinguished from its germ cell counterparts given its placental origin but usually exists in combination with other germ cell tumors. It is VERY aggressive and metastasizes early to the lungs, liver and bone. Will see necrotic mass.

IMMATURE MALIGNANT TERATOMA germ cell tumor

This tumor resembles tissue in an embryo and is characterized by its solid areas of necrosis and hemorrhage.

FOLLICULAR CYSTS

This type of nonneoplastic lesion is more of a physiologic occurance than a pathologic occurence and originates from the unruptured graffian follicles or in follicles that have ruptured and then immediately sealed up.. It is often filled with serous fluid. What is the name of this lesion?

BRENNER SURFACE EPITHELIAL TUMOR

This type of tumor is distinguished from others because its epithelial component consists of nests of transitional type epithelial cells with unilateral firm, white solid masses with cystic nests of cells with grooved nuclei.

BRENNER SURFACE EPITHELIAL TUMOR

This type of tumor tends to be solid in nature and may pop up in conjunction with a cystic teratoma. Epithelial nests within the stroma are common. Distinguished by its transitional like epithelia.

SERTOLI-LEYDIG CELL TUMOR of the ovary

This type of tumor will produce masculinzation or defeminization with some estrogenic effects. Peak incidence is in the 2nd and 3rd decades of life but can occur in women of all ages. Presents unilaterally as a solid, grad to golden brown tumor.

SERTOLI-LEYDIG tubule cells in the ovary sertoli-leydig cell tumor

This type of tumor will produce masculinzation or defeminization with some estrogenic effects. What type of cells are present here? What's the pathology?

JUVENILE GRANULOSA CELL TUMOR

This variant of a hormonally active tumor occurs in younger individuals. Can see some primitive gland-like structures. Known to pump out large amounts of estrogen.

1) Tubal 2) ovarian 3) cornual 4) abdominal *GET A PREGNANCY TEST*

What are 4 potential locations for ectopic pregnancies? What should you do if a woman of child-bearing age comes comes in complaining of abdominal pain?

Call-Exner bodies are small glandlike structures found in granulosa-theca cell tumors of the ovary.

What are CALL-EXNER bodies?

These are cells with extensive mucin that will displace the nucleus all the way to the edge of the cell. Seen in gastric carcinoma

What are SIGNET RING cells? In what GI pathology do we see them?

SEROUS & MUCINOUS While both are cystic, they can be differentiated by the type of material inside the cyst. Serous has more watery fluid material while mucinous has more mucinoid, gelatinous type of material inside. Serous tumors tend to be BILATERAL, while Mucinous tumors tend to be more UNILATERAL. Serous tumors are lined by columnar cells + CILIA Mucinous tumors are lined by tall columnar cells + apical mucin -CILIA

What are the 2 types of CYSTIC surface epithelial tumors? How would you differentiate the two?

1) Sertoli-Leydig 2) Fibroma/thecoma/fibrothecoma 3) Granulosa cell tumor

What are the 3 types of SEX CORD STROMAL tumors?

1) Teratomas 2) Dysgerminomas 3) Endodermal Sinus (yolk sac) tumors 4) Ovarian Choriocarcinoma

What are the 4 types of GERM CELL tumors?

1) Follicular cysts 2) Luteal Cysts 3) Polycystic Ovaries 4) Stromal hyperthecosis

What are the 4 types of NONneoplastic and functional cysts in the ovary?

Placenta poorly attached to wall of the tube -> Cause a tubal hematoma; expands as child grows and may rupture *Rupture can be fatal* -Sometimes tubal pregnancy can regress and remain asymptomatic -Sometimes tubal pregnancy may be extruded from fimbriated end into abdominal cavity, mesentery, peritoneal wall ---Usually child will be spontaneously aborted; Not as much of a danger because it has room to grow

What are the clinical consequences of ectopic pregnancy?

High grade -> BRCA1 and BRCA2, as well as p53 Low grade from borderline -> KRAS and BRAF oncogene mutations

What are the genetic risk factors for high grade serous surface epithelial tumors? For low grade tumors arising from borderline tumors?

1) Adenomatoid tumors: solid, white, benign 2) Carcinoma: rare, usually papillary adenocarcinoma, prognosis determined by stage

What are two tumors of the fallopian tube?

See increased LEUTININZING HORMONE (LH) LH acts on Theca interna cells to produce androgens, these androgens go to granulosa cells where under the influence of FSH will produce estrogen -> will see excess estrogen too

What hormone is greatly increased in PCOS? Describe the pathogenesis by which there will be excess androgen production.

ASCITES

What is a clinical finding classic of serous tumor spread to the peritoneum?

INHIBIN - high levels in tissue and serum are diagnostic of granulosa-theca cell tumors

What is an important serum marker for granulosa-theca cell tumor?

YOLK SAC TUMOR

What is another name for the endodermal sinus tumor?

OVARIAN CANCER

What is the 5th most common cancer in women?

1. Severe abdominal pain occurring approx. six weeks after a menstrual period (take history) 2. Signs of an acute abdomen (rigidity, rebound tenderness, guarding)

What is the clinical course of an ectopic pregnancy?

NULLIPARITY Others: Family hx, heritable mutations, gonadal dysgenesis, BRCA1, BRCA2

What is the greatest risk factor for Ovarian Cancer? What are some of the other risk factors?

Immature resembles tissue in an EMBRYO, while mature resembles ADULT tissue.

What is the key distinguishing feature between immature and mature teratomas?

FALLOPIAN TUBES

What is the most common location for ectopic pregnancy?

SEROUS CYSTADENOCARCINOMAS with 30% expressing HER2/NEU oncogene with a poor prognosis

What is the most common type of ovarian cancer?

SCHILLER DUVAL BODIES

What is the name for the glomerulus like structure found in endodermal sinus tumors that are constructed of a central blood vessel enveloped by germ cells within a space lined by germ cells?

DYSGERMINOMA

What is the name for the ovarian counterpart to the seminoma of the testes?

PSEUDOMYXOMA PERITONEI This is a clinical condition marked by extensive mucinous ascites, cystic epithelial implants on the peritoneal surfaces, adhesions, and frequent involvement of the ovaries. *Pseudomyxoma peritonei, if extensive, may result in intestinal obstruction and death.*

What is the name of the clinical condition that arises from the implantation of a mucinous cysts on the peritoneal structures? Why is this condition important to recognize? *This is often a PRIMARY tumor of the appendix that spread to the ovary*

LUTEAL CYSTS

What is the name of the type of nonneoplastic lesion that is lined by a rim of bright yellow luteal tissue that contains luteinized granulosa cells and carries the risk of rupturing into peritoneal space?

Clusters or sheets of cuboidal or polygonal cells.

What is the thecomal component of granulosa theca cell tumors?

POLYCYSTIC OVARIAN SYNDROM (PCOS)

What nonneoplastic lesion has the following clinical presentation: anovulation, obesity, hirsuitism and virulism with ovaries becoming twice its normal size with multiple subcortical cysts and increased production of androgens?

STROMAL HYPERTHECOSIS

What nonneoplastic lesion is classically seen in postmenopausal women, results in more striking virulization features and will have the following morphological features: uniform enlargment of the ovary with a tan/white appearance with hypercellular stroma and luteinized stroma cells. This lesion is usually bilateral.

Only 1%

What percentage of mature teratomas undergo malignant transformation in the following elements: squamous cell carcinoma, thyroid carcinoma, melanoma?

GRANULOSA-THECA CELL TUMOR

What sex cord stromal tumor is hormonally active producing large amounts of estrogen and is associated with endometrial hyperplasia, endometrial carcinoma and fibrocystic changes in the breast?

CARCINOID teratoma arises from intestinal epithelium and may produce CARCINOID SYNDROME

What subcategory of germ cell tumors arises from intestinal epithelium? What clinical syndrome does it produce?

The STRUMA OVARII- this is composed of THYROID tissue and associated with hypERthyroidism

What subcategory of germ cell tumors have a clinical presentation of hyperthyroidism? Why?

BRENNER surface epithelial cell tumor and GRANULOSA-THECA cell sex cord stromal tumor

What two pathologies of the ovary will you see "grooved coffee been" nuclei?

PID and CHRONIC SALPINGITIS

What two things are associated with ectopic pregnancy?

SURFACE EPITHELIAL TUMORS

What type of ovarian neoplasm makes up 2/3 of all ovarian tumors and 90% of all malignant ovarian tumors?

ORAL CONTRACEPTIVE USE (OCP) This decreases a woman's risk because it is believed that each time a woman ovulates, there is trauma to the surface epithelium due to explulsion of the oocyte. The MOA of OCPs is to prevent ovulation and therefore helps to decrease the amount of trauma induced to surface epithelium

While nulliparity, family hx, and heritable mutations all increase a woman's risk for ovarian cancer, what is one thing that actually DECREASES a woman's risk for ovarian cancer? Why?

TALL COLUMNAR CELLS WITH APICAL MUCIN and NO CILIA

While the SEROUS cystadenoma is lined by columnar cells with CILIA, the MUCINOUS cystadenoma is lined by _________.

KRAS

While the SEROUS type of surface epithelial neoplasm carries genetic risk factors of BRCA1 and BRCA2, the MUCINOUS type carries genetic risk factor of _________.

SMOKING

While the SEROUS type of surface epithelial neoplasm carries risk factors of lower parity, the MUCINOUS type carries risk factor of _________.

MUCINOUS CYSTADENOMA

Woman in her 30s comes into your office with complaining of pelvic pain. You take her history and note her 30pack yr history of smoking. Upon doing a biopsy, you note the findings above and see columnar cells lining a cyst with cloudy appearance inside. You do not see cilia. What is her diagnosis?

CYSTADENOFIBROMA

________________ is a benign tumor with pronounced proliferation of fibrous stroma under the columnar lining epithelium. These tumors tend to be small and multilocular with simple papillary processes; borderline tumors are uncommon.

MUCINOUS SURFACE EPITHELIAL TUMOR

_____________type of tumor tends to be less bilateral, contains gelatinous material, occurs in middle adult life, grow large with 80% making up the borderline or benign type.

KRUKENBURG tumor

signet ring cells can be seen here infiltrating extensively the walls of the ovaries. What metastatic tumor presents with signet ring cells?