Neoplastic Diseases of the Ovary PDF

NEOPLASTIC DISEASES OF THE OVARY, FALLOPIAN TUBE & PERITONEAL CARCINOMA Carol H. Pacioles-Flavier, MD, FPOGS, FSGOP Obstetrician-Gynecologist Gynecologic Oncologist  OBJECTIVES Ø Define neoplastic ovarian tumors Ø Clas...

NEOPLASTIC DISEASES OF THE OVARY, FALLOPIAN TUBE & PERITONEAL CARCINOMA Carol H. Pacioles-Flavier, MD, FPOGS, FSGOP Obstetrician-Gynecologist Gynecologic Oncologist  OBJECTIVES Ø Define neoplastic ovarian tumors Ø Classify the different types of ovarian tumors Ø Describe each type of ovarian tumors epidemiology gross and histologic appearance behavior and prognosis management  OBJECTIVES Ø Enumerate the staging classification for ovarian tumors Ø Discuss the different screening modalities for ovarian tumors Ø Discuss fallopian tube cancer and peritoneal carcinoma  INCIDENCE u 2nd most common malignancy of the female genital tract u Most frequent cause of death from gynecologic neoplasms u Increases with age u US Cancer Statistics (2015): v 21,290 new cases yearly v 14,180 deaths  CANCER IN THE PHILIPPINES Leading Cancer Sites in Females* Rank Site Number Percentage 1 Breast 20267 33 2 Cervix Uteri 7289 12 3 Colon/Rectum 4375 7 4 Lung 3684 6 5 Ovary 2657 4 6 Liver 2579 4 7 Thyroid 2464 4 8 Corpus Uteri 2451 4 9 Leukemia 2104 3 10 Oral Cavity 1247 2 *Based on the 2015 Philippine Cancer Facts and Estimates  EPIDEMIOLOGY CLEAR-CUT CAUSE NOT DEFINED  PUTATIVE ASSOCIATIONS OF INCREASING AND DECREASING RISKS OF EPITHELIAL OVARIAN CARCINOMA* INCREASES DECREASES Age Breastfeeding Diet Oral Contraception Family History Pregnancy Industrialized Country Tubal Ligation and Hysterectomy with Ovarian Conservation Infertility Nulliparity Ovulation / Ovulatory Drugs Talc (?) *Herbst AL. The epidemiology of ovarian cancer and the current status of tumor markers to detect disease. Am J. Obstet Gynecol; 1994:170(4): 1099-1105.  RISK FACTORS FOR EPITHELIAL OVARIAN CARCINOMA REPRODUCTIVE GENETIC Ø Low parity Ø Breast-Ovarian Use of fertility Ø cancer syndrome drugs Ø Lynch type II “Incessant Ø Ø Site-specific ovulation” ovarian cancer syndrome CLASSIFICATION OF OVARIAN NEOPLASMS (WORLD HEALTH ORGANIZATION) EPITHELIAL OVARIAN NEOPLASMS 65% 2/3 of all ovarian neoplasms Arising from inclusion cysts lined with surface (coelomic) epithelium Recapitulate the Mullerian- duct-derived epithelium of the female reproductive system  Epithelial Tumors INTERMEDIATE BENIGN MALIGNANT (Low Malignant (Adenoma) (Adenocarcinoma) Potential) DEFINITION OF TERMS Papillary The tumor has papillae Used as a prefix (PAPILLARY adenocarcinoma) Cyst The tumor has cystic structures Used as a prefix (CYSTadenoma) Fibroma The tumor is predominantly ovarian stroma Used as a suffix (adenoFIBROMA)  Epithelial Ovarian Tumor Cell Types Endometrioid Mucinous Clear Cell Epithelial Serous Ovarian Brenner Tumors  25-50% of all ovarian neoplasms Differentiated from 35-40% of all ovarian the endosalpinx malignancies SEROUS TUMORS Aggressive tumor Typically occur in with extensive women > 40 years metastasis on the old ovarian surface and abdomen  BENIGN SEROUS TUMORS Unilateral, 1-10 cm Inner surface smooth, External surface smooth some with small papillary Glistening, thin-walled projections Contain clear fluid Ciliated cuboidal or columnar epithelium Single layer of epithelium MALIGNANT SEROUS TUMORS Bilateral in 2/3 of cases Generally cystic, papillary to entirely solid masses Large, hemorrhagic papillary excrescences Glands and tubules in cribriform pattern Stromal invasion  15-25% of all ovarian neoplasms Differentiated from 6-10% of all ovarian the endocervix malignancies MUCINOUS TUMORS Typically occur in Tend to be the largest women 30-60 of all ovarian tumors years old  BENIGN MUCINOUS TUMORS Mostly unilateral Mucin-filled Mucin-filled columnar cells Smooth inner with basal nuclei lining  MALIGNANT MUCINOUS TUMORS Large ovarian tumors Crowded glands, nuclear atypia, with stromal invasion Cystic with solid areas, with necrosis and hemorrhage  5% of all ovarian neoplasms Differentiated from 15-25% of all ovarian the endometrium malignancies ENDOMETRIOID TUMORS May be seen in Typically occur in conjunction with women 50-60 years endometriosis and old ovarian endometriomas  ENDOMETRIOMA Ø NOT classified as a neoplasm Ø Unilocular Ø Contain chocolate-like fluid Ø Associated with dysmenorrhea and infertility ENDOMETRIOID ADENOCARCINOMA Mostly Contain Mimics With epithelium uni- bloody stromal of the lateral fluid endo- invasion and metrium solid Glands are in a cribriform pattern  10 mm in greatest dimension IIIA2 – microscopic extrapelvic peritoneal involvement +/- retroperitoneal lymph nodes FIGO STAGING FOR OVARIAN CARCINOMA STAGE III B – macroscopic peritoneal metastasis up to 2cm C – macroscopic peritoneal metastasis > 2cm FIGO STAGING FOR OVARIAN CARCINOMA STAGE IV A – pleural effusion with positive cytology B – parenchymal metastasis and metastasis to extra abdominal organs CARCINOMA OF THE OVARY SURVIVAL BASED ON FIGO STAGE* STAGE 5-YEAR SURVIVAL (%) IA 94 IB 92 IC 85 IIA 78 IIB 73 IIIA 59 IIIB 52 IIIC 39 IV 17 *Data from American Cancer Society (2004-2010). TREATMENT FOR OVARIAN CARCINOMA SURGERY TREATMENT FOR OVARIAN CARCINOMA CHEMOTHERAPY TREATMENT FOR OVARIAN CARCINOMA RADIOTHERAPY  HISTOGENESIS OF GERM CELL TUMORS GERM CELL DYSGERMINOMA TOTIPOTENTIAL CELLS EMBRYONAL CARCINOMA EMBRYONAL CARCINOMA ECTODERM, EXTRAEMBRYONIC MESODERM, STRUCTURES ENDODERM ENDODERMAL SINUS TUMOR CHORIOCARCINOMA TERATOMA  GERM CELL TUMORS Derived from 2nd most frequent 20-25% of all germ cells of the type of ovarian ovarian tumors ovary neoplasm WHO CLASSIFICATION OF GERM CELL TUMORS DYSGERMINOMA *Endodermal Sinus Tumor *Embryonal Carcinoma *Polyembryoma *Choriocarcinoma *Teratomas (Mature, Immature) *Dermoid Cyst (Mature Cystic Teratoma) *Monodermal and Highly Specialized (Struma ovarii, Carcinoid, Others) *Mixed Forms  Tissues that Arise from a single recapitulate the 3 germ with an XX layers of the karyotype developing embryo TERATOMAS Benign cystic Malignant teratomas (IMMATURE) – mostly (DERMOIDS) – most neuroepithelium common  DERMOIDS Ø Primarily occur in reproductive years Ø May have ectoderm, mesoderm and endoderm components Ø Usually unilateral, 10-15% bilateral Ø Treatment may be cystectomy or unilateral oophorectomy Ø May undergo malignant transformation  DYSGERMINOMAS Ø Most common type of malignant germ cell tumors Ø Primitive germ cells with stroma infiltrated by lymphocytes Ø Analogous to seminoma Ø Mostly bilateral in 10% of cases Ø May produce HCG  YOLK SAC TUMORS Ø Also known as Endodermal Sinus Tumors Ø Resembles the yolk sac of the rodent placenta Ø Secretes alpha feto protein which serves as a useful tumor marker Ø Rapidly growing Ø Pathognomonic feature is the presence of Schiller- Duvall bodies Schiller-Duvall body  CHORIOCARCINOMAS Ø Non-gestational type Ø Highly malignant and rare Ø Consists of malignant cytotrophoblasts and syncitiotrophoblasts Ø HCG is a useful tumor mrker Ø Mostly develops in women < 20 years old  GERM CELL TUMORS Immature Embryonal Poly- Mixed Teratoma Carcinoma embryoma Germ Cell Very rare; mostly Mostly consisting Tumors contain contain of immature primitive embryonal neuroepi- embryonal bodies thelium cells resembling early embryos Derived from the sex cords of the ovary & Accounts for 6% of the specialized ovarian neoplasms stroma of the developing gonad SEX-CORD STROMAL TUMORS Most hormonally May have female and functioning ovarian male derivatives tumors  GRANULOSA-THECA CELL TUMORS Ø Consist primarily of granulosa cells and a varying proportion of theca cells, fibroblasts, or both Ø May produce estrogen causing vaginal bleeding Ø Low grade malignant character Call-Exner body Ø FOXL2 mutation Ø Call-Exner bodies (eosinophilic bodies surrounded by granulosa cells)  THECOMAS & FIBROMAS Ø Benign tumor Ø Consists entirely of stroma (theca) cell – THECOMA Ø Consists of spindle cells - FIBROMA THECOMA Ø Peri- and menopausal women Ø Excision of tumor is usually curative Ø Fibromas are associated with Meigs syndrome FIBROMA  SERTOLI-LEYDIG CELL TUMORS Ø Very rare Ø Sex cord (Sertoli) and Stromal (Leydig) cells are present in varying amounts Ø Young women / reproductive age Ø Cause masculinization & hirsutism (virilization) Ø Low grade malignancy Ø DICER1 mutation  SEX CORD – STROMAL TUMORS Gynandro Sex Cord Leydig Cell Metastatic blastoma Tumors and Hilus Ovarian with Cells Tumors Annular Tumors Rare & Tubules consists of Hyaline granulosa Kruken- bodies berg’s & Sertoli Prominent known as Tumor cells tubular crystalloids pattern of Reinke FALLOPIAN TUBE AND PERITONEAL CANCER  FALLOPIAN TUBE CANCER u Rare u 0.2% of cancers among women u Arise from the epithelial lining of the fallopian tube fimbria u BRCA mutation u Risk factors v Infertility v Low parity v Early menarche v Late menopause  PERITONEAL CARCINOMA u 1st described by Swerdlow in 1959 u Diffusely involves the peritoneal surfaces while sparing or minimally involving the ovaries and fallopian tubes u Incidence is 0.46 per 100,000 in the US u Risk factors similar to ovarian and fallopian tube cancer  PERITONEAL CARCINOMA u THEORIES v Malignant transformation of the germinal epithelium v Field effect of the coelomic and germinal epithelium u Diagnosis of exclusion  FALLOPIAN TUBE PERITONEAL CANCER CANCER CLINICAL FINDINGS Mean age is 58 years Age range from 63-66 old years old Mostly asymptomatic Pain, abdominal Latzko’s triad distention, pressure, GI (serosanguineous symptoms vaginal discharge, colicky pain & a mass) DIAGNOSIS Ultrasound Ultrasound CA-125 Levels CA-125 Levels Other imaging (CT Other imaging (CT Scan, MRI, PET scans Scan, MRI, PET scans  FALLOPIAN TUBE CARCINOMA Ø Arise in either tube with similar frequency Ø Fimbriated end is grossly occluded in 50% of cases Ø 80-90% are serous adenocarcinomas FALLOPIAN TUBE CANCER u Pathologic diagnostic criteria (Hu, 1959 & Sedlis, 1978) u The main tumor lies in the tube and arises from the endosalpinx u The histologic pattern reproduces the papillary epithelium of the tubal mucosa u A transition can be demonstrated between the malignant and non-malignant tubal epithelium u The ovaries and uterus are normal or contains less tumor than the fallopian tube  PERITONEAL CARCINOMA u Pathologic diagnostic criteria (GOG) u Both ovaries must be physiologically normal in size or enlarged by a benign process u Involvement in the extraovarian sites must be greater than the involvement on the surface of either ovary u Microscopically, the ovarian component must be one of the following: u Nonexistent u Confined to the ovarian surface epithelium with no evidence of cortical invasion u Involving ovarian surface epithelium and underlying cortical stroma smaller than 5x5 mm u Tumor smaller than 5x5 mm within the ovarian substance, with or without surface disease u The histologic and cytologic characteristics of the tumor must be predominantly of the serous type similar or identical to ovarian serous papillary adenocarcinoma TREATMENTFOR FALLOPIAN TUBE & PERITONEAL CARCINOMA SURGERY TREATMENTFOR FALLOPIAN TUBE & PERITONEAL CARCINOMA CHEMOTHERAPY  SUMMARY Ø Defined neoplastic ovarian tumors Ø Classified the different types of ovarian tumors Ø Described each type of ovarian tumors epidemiology gross and histologic appearance behavior and prognosis management  SUMMARY Ø Enumerated the staging classification for ovarian tumors Ø Discussed the different screening modalities for ovarian tumors Ø Discussed fallopian tube cancer and peritoneal carcinoma NEOPLASTIC DISEASES OF THE OVARY, FALLOPIAN TUBE & PERITONEAL CARCINOMA Carol H. Pacioles-Flavier, MD, FPOGS, FSGOP Obstetrician-Gynecologist Gynecologic Oncologist