Ovarian Cancer

Overview

Definition

Ovarian cancer is a malignant tumor Tumor Inflammation arising from the ovarian tissues.

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency:
  • 11.4 per 100,000 women annually
  • The lifetime risk of ovarian cancer among women in the US is approximately 1.3%.
  • 3rd-most common gynecologic cancer (after cervical and uterine)
• Mortality Mortality All deaths reported in a given population. Measures of Health Status impact:
  • Leading cause of gynecologic cancer death in women
  • 5th-most common cause of cancer-related deaths in women

Risk factors

• Postmenopausal women
• Family history Family History Adult Health Maintenance of breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer and/or ovarian cancer
• Increasing age
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
• Early menarche Menarche The first menstrual cycle marked by the initiation of menstruation. Menstrual Cycle and/or late menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause (↑ number of menstrual cycles)
• Nulliparity
• Endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis

Protective factors

Several common factors significantly reduce the risk of ovarian cancer, including:

• Prolonged use of oral contraceptives
• Tubal ligation Tubal Ligation Nonhormonal Contraception
• Hysterectomy
• Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
• Parity Parity The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. Pregnancy: Diagnosis, Physiology, and Care
• Bilateral salpingo-oophorectomy (BSO) is the removal of fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy and ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy:
  • Performed prophylactically in women with known mutations, such as BRCA mutations, which put them at high risk for ovarian cancer
  • Cancer risk is not entirely eliminated despite surgical excision.

Classification

Overview of ovarian tumor Tumor Inflammation classification

• Ovarian tumors are classified according to the type of cell from which they originate:
  • Epithelial tumors
  • Germ cell tumors
  • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria cord-stromal tumors
  • Metastatic tumors (originating in other tissues and metastasizing to the ovary)
• There are multiple histologic subtypes within each major tumor Tumor Inflammation class.
• Tumors may be classified as either:
  • Benign Benign Fibroadenoma (adenomas): neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors exhibiting abnormal growth but not invading into the surrounding tissue
  • Borderline/low malignant potential ( LMP LMP The 1st day of a woman’s LMP Pregnancy: Diagnosis, Physiology, and Care) tumors: malignant neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors that are not very aggressive and have excellent prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
  • Malignant (carcinomas or adenocarcinomas): tumors that invade into the surrounding tissue

Epithelial ovarian tumors

Epithelial ovarian carcinomas (EOCs) originate from surface epithelial cells and account for 90%‒95% of ovarian malignancies. Major types of EOCs include:

• Serous adenocarcinoma:
  • Most common type accounting for 50% of malignant EOCs
  • Papillary structures within the cystic Cystic Fibrocystic Change area
  • Psammoma bodies Psammoma Bodies Cellular Accumulations:
    • Intracellular calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes deposits
    • Key feature of serous EOCs
  • Usually high grade at diagnosis
  • Generally associated with a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
• Endometrioid adenocarcinoma Endometrioid Adenocarcinoma Endometrial Hyperplasia and Endometrial Cancer:
  • Approximately 15%‒20% of malignant EOCs
  • Complex glandular architecture with back-to-back glandular growth
  • Better prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas compared with serous types:
    • Typically low grade at diagnosis
    • More chemosensitive
  • Associated with:
    • Coexisting endometrial adenocarcinoma (15%‒20% of cases) 
    • Endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis (40%‒50% of cases)
• Clear cell adenocarcinoma:
  • Approximately 5%‒10% of malignant EOCs
  • Present as a large cystic Cystic Fibrocystic Change mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (average size: 15 cm)
  • Sheets of cells with clear cytoplasm
  • Typically presents at an early stage
  • Poor chemosensitivity Chemosensitivity Tumor Lysis Syndrome
  • Associated with endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis
• Mucinous adenocarcinoma:
  • Large cystic Cystic Fibrocystic Change masses that are typically 8‒20 cm, but can be much larger
  • Pseudomyxoma peritonei:
    • Clinical syndrome of abundant mucoid material in the abdominopelvic cavity
    • While possible in mucinous EOCs, pseudomyxoma peritonei is typically associated with mucinous tumors of the appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy
• Less common types of EOC:
  • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC)
  • Small cell carcinoma Small cell carcinoma An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. Lung Cancer
  • Transitional cell tumors: Brenner tumors
  • Mixed carcinoma
  • Undifferentiated carcinoma

Germ cell tumors

Ovarian germ cell tumors (OGCTs) originate from primordial germ cells Primordial germ cells Gametogenesis (i.e., primordial oocytes Oocytes Female germ cells derived from oogonia and termed oocytes when they enter meiosis. The primary oocytes begin meiosis but are arrested at the diplotene state until ovulation at puberty to give rise to haploid secondary oocytes or ova (ovum). Ovaries: Anatomy).

• May be benign Benign Fibroadenoma or malignant
• Malignant OGCTs account for 5% of malignant ovarian cancers.
• Typically arise in young women aged 10‒30 years
• Excellent prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas because:
  • Typically present at stage I
  • Excellent chemosensitivity Chemosensitivity Tumor Lysis Syndrome

Histologic types of malignant OGCTs:

• Dysgerminomas:
  • Most common malignant OGCT accounting for approximately 30% of cases
  • Less aggressive than many other ovarian cancers
  • Composed of undifferentiated germ cells Germ Cells The reproductive cells in multicellular organisms at various stages during gametogenesis. Gametogenesis
  • Associated with gonadal dysgenesis Gonadal dysgenesis A number of syndromes with defective gonadal developments such as streak gonads and dysgenetic testes or ovaries. The spectrum of gonadal and sexual abnormalities is reflected in their varied sex chromosome (sex chromosomes) constitution as shown by the karyotypes of 45, X monosomy (Turner syndrome); 46, XX (gonadal dysgenesis, 46xx); 46, XY (gonadal dysgenesis, 46, xy); and sex chromosome mosaicism. Their phenotypes range from female, through ambiguous, to male. This concept includes gonadal agenesis. Wilms Tumor (which occurs in phenotypic females with a Y chromosome Y chromosome The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained. Basic Terms of Genetics):
    • 46XY pure gonadal dysgenesis Pure gonadal dysgenesis 46,XX gonadal dysgenesis is a disorder present in individuals who are phenotypic females with normal karyotypes of 46,XX and who have streak gonads with no functional ovarian tissue. It is also called “pure gonadal dysgenesis” to differentiate these patients from those who present with the phenotype of Turner’s syndrome. 46,XX Gonadal Dysgenesis
    • 45X/46XY Turner-mosaic mixed gonadal dysgenesis Gonadal dysgenesis A number of syndromes with defective gonadal developments such as streak gonads and dysgenetic testes or ovaries. The spectrum of gonadal and sexual abnormalities is reflected in their varied sex chromosome (sex chromosomes) constitution as shown by the karyotypes of 45, X monosomy (Turner syndrome); 46, XX (gonadal dysgenesis, 46xx); 46, XY (gonadal dysgenesis, 46, xy); and sex chromosome mosaicism. Their phenotypes range from female, through ambiguous, to male. This concept includes gonadal agenesis. Wilms Tumor
    • 46XY complete androgen insensitivity syndrome Androgen insensitivity syndrome Androgen insensitivity syndrome (AIS) is an X-linked recessive condition in which a genetic mutation affects the function of androgen receptors, resulting in complete (CAIS), partial (PAIS), or mild (MAIS) resistance to testosterone. All individuals with AIS have a 46,XY karyotype; however, phenotypes vary and include phenotypic female, virilized female, undervirilized male, and phenotypic male individuals. Androgen Insensitivity Syndrome
  • Develop from malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology of gonadoblastomas ( benign Benign Fibroadenoma OGCTs)
• Immature teratomas:
  • Approximately 20% of malignant OGCTs
  • Typically solid masses with some cystic Cystic Fibrocystic Change areas
  • Contain a disordered mix of all 3 primary germ layer tissue types ( ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation, mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation, and endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation)
  • Neuroectoderm Neuroectoderm Development of the Nervous System and Face typically predominates.
  • ↑ Risk of torsion due to the “lopsided” nature of masses
  • Develop from malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology of mature teratomas ( benign Benign Fibroadenoma OGCTs that are also known as dermoid cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change)
• Yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development tumors:
  • Previously known as endodermal sinus tumors
  • Approximately 15% of malignant OGCTs
  • Derived from cells of the primitive yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development
  • Schiller-Duval bodies: glomerulus-like structure composed of central blood vessels surrounded by germ cells Germ Cells The reproductive cells in multicellular organisms at various stages during gametogenesis. Gametogenesis
  • Most dangerous OGCT
• Choriocarcinoma Choriocarcinoma A malignant metastatic form of trophoblastic tumors. Unlike the hydatidiform mole, choriocarcinoma contains no chorionic villi but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (trophoblasts). It is characterized by the large amounts of chorionic gonadotropin produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin. Gestational Trophoblastic Disease:
  • Derived from germ cells Germ Cells The reproductive cells in multicellular organisms at various stages during gametogenesis. Gametogenesis, but have an appearance similar to gestational choriocarcinoma Choriocarcinoma A malignant metastatic form of trophoblastic tumors. Unlike the hydatidiform mole, choriocarcinoma contains no chorionic villi but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (trophoblasts). It is characterized by the large amounts of chorionic gonadotropin produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin. Gestational Trophoblastic Disease (derived from trophoblastic tissue found in pregnancies)
  • Worse prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas compared with that of gestational choriocarcinoma Choriocarcinoma A malignant metastatic form of trophoblastic tumors. Unlike the hydatidiform mole, choriocarcinoma contains no chorionic villi but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (trophoblasts). It is characterized by the large amounts of chorionic gonadotropin produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin. Gestational Trophoblastic Disease
• Other less common types:
  • Embryonal carcinoma
  • Mixed germ cell tumors

Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria cord-stromal tumors (SCSTs)

Ovarian SCSTs originate from sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria cord cells, stromal cells, or both.

• May be benign Benign Fibroadenoma or malignant
• Malignant SCSTs account for approximately 5% of malignant ovarian cancers.
• Most common in perimenopausal women (average age at diagnosis: 50 years)

Histologic types of SCSTs:

• Granulosa cell Granulosa cell Supporting cells for the developing female gamete in the ovary. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the oocyte in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the ovum in the graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors. Puberty tumors (often malignant):
  • 90% (most common type) of malignant SCSTs
  • Made up of granulosa cells (cells that normally line the developing follicles)
  • Usually secrete estrogens; occasionally secrete androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens → present with hormonally driven symptoms (e.g., abnormal bleeding, virilization)
  • Call-Exner bodies: small follicles with eosinophilic material
• Theca cell tumors (usually benign Benign Fibroadenoma):
  • Much rarer than granulosa cell Granulosa cell Supporting cells for the developing female gamete in the ovary. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the oocyte in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the ovum in the graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors. Puberty tumors
  • Composed of theca cells Theca cells The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature ovarian follicle. Thecal interstitial or stromal cells are steroidogenic, and produce primarily androgens which serve as precursors of estrogens in the granulosa cells. Puberty (supportive cells that produce hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types)
  • Often secrete estrogens and/or androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
• Fibroma ( benign Benign Fibroadenoma):
  • Benign Benign Fibroadenoma tumor Tumor Inflammation arising from fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis in connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
  • The most common SCST overall
• Fibrosarcoma (malignant):
  • Malignant soft-tissue tumor Tumor Inflammation (i.e., sarcoma) arising from fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis in the connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
  • Extremely rare
• Sertoli-Leydig cell tumors:
  • Abnormal cells that are typically only found in men (but found in women with this condition)
  • Secrete androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens → present with virilization
  • Rare

Pathophysiology

Pathogenesis

• Ovarian cancer develops as a result of cellular mutations → leads to dysregulated cellular growth → ↑ proliferation → tumor Tumor Inflammation
• Mutations may:
  • Arise de novo (a majority of mutations)
  • Be genetically inherited
• Some tumors undergo progression from benign Benign Fibroadenoma cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change → borderline/ LMP LMP The 1st day of a woman’s LMP Pregnancy: Diagnosis, Physiology, and Care tumors → invasive carcinoma
• Many EOCs are actually believed to originate from the epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology of adjacent fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy fimbriae Fimbriae Thin, hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria, particularly enterobacteriaceae and Neisseria. Unlike flagella, they do not possess motility, but being protein (pilin) in nature, they possess antigenic and hemagglutinating properties. They are of medical importance because some fimbriae mediate the attachment of bacteria to cells via adhesins. Bacterial fimbriae refer to common pili, to be distinguished from the preferred use of ‘pili’. Escherichia coli (thus, tubal ligation Tubal Ligation Nonhormonal Contraception and salpingectomies ↓ risk of EOC).
• Theory: regular Regular Insulin ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle over a prolonged period leads to an increased need to repair the surface of the ovary → constant repair, inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, and proliferation can lead to the accumulation of genetic mutations Genetic Mutations Carcinogenesis responsible for cancer development

Associated genetic mutations Genetic Mutations Carcinogenesis

Some mutations are commonly associated with ovarian cancers, including:

• BRCA1 and 2:
  • Tumor-suppressor genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure involved in DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure repair
  • Most commonly inherited mutations associated with ovarian cancer
  • Inherited in an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance pattern
  • BRCA1: approximately 40% lifetime risk of ovarian cancer
  • BRCA2: approximately 20% lifetime risk of ovarian cancer
• P53 (de novo or as part of Li-Fraumeni syndrome)
• Some of the mismatch repair Mismatch repair A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Exonucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure that cause Lynch syndrome Lynch syndrome Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome:
  • MLH1
  • MSH2
  • MSH6
• Other genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure involved in the double-strand break repair system:
  • CHEK2
  • RAD61
  • BRIP1
• KRAS mutations are common in mucinous carcinomas.

Mechanisms of spread

Ovarian cancers spread via:

• Direct local extension Extension Examination of the Upper Limbs
• Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis within the peritoneal cavity Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of winslow, or epiploic foramen. Peritoneum: Anatomy:
  • Omentum Omentum Peritoneum: Anatomy
  • On the mesentery Mesentery A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. Peritoneum: Anatomy and serosa of the bowel
  • Undersurface of the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy or surface of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
• Lymphatic invasion:
  • Para-aortic lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes (Recall: Primary blood supply to the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy is via the ovarian arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology, directly off the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy.)
  • Pelvic lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes
• Hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases dissemination to distant sites (most commonly the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy)

Clinical Presentation

Women with early disease (especially EOCs) tend to be asymptomatic or present with vague, nonspecific complaints. Most women with EOCs especially tend to present later with signs/symptoms associated with metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis.

• Systemic signs of disease:
  • Loss of appetite
  • Unexpected weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
• Gynecologic symptoms:
  • Pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Irregular uterine bleeding Irregular uterine bleeding Variation between shortest and longest cycles is ≥ 8‒10 days Abnormal Uterine Bleeding (with hormone-secreting SCSTs)
  • Dyspareunia Dyspareunia Recurrent genital pain occurring during, before, or after sexual intercourse in either the male or the female. Primary Ovarian Insufficiency ( pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways with intercourse)
  • Palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast on pelvic exam
• GI/abdominal:
  • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Bloating Bloating Constipation/abdominal distension
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea or constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Large palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast on abdominal exam (especially with mucinous and clear cell EOCs)
  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
  • Bowel obstruction Bowel obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis
• Genitourinary:
  • Increased urinary frequency
  • Urinary urgency Urinary Urgency Normal Pressure Hydrocephalus
• Musculoskeletal:
  • Back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Weakness
• Endocrine (common with hormone-secreting SCSTs):
  • Breast development in young girls/breast growth in adults
  • Abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding
  • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility due to anovulation Anovulation Suspension or cessation of ovulation in animals or humans with follicle-containing ovaries (ovarian follicle). Depending on the etiology, ovulation may be induced with appropriate therapy. Polycystic Ovarian Syndrome, as estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy and testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens suppress ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
  • Androgenic symptoms:
    • Acne
    • Hirsutism Hirsutism A condition observed in women and children when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated androgens from the ovaries, the adrenal glands, or exogenous sources. The concept does not include hypertrichosis, which is an androgen-independent excessive hair growth. Polycystic Ovarian Syndrome
    • Virilization in young girls
• Other signs of advanced disease:
  • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
  • Palpable lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy in the groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination
  • Sister Mary Joseph nodule Nodule Chalazion ( metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis to the umbilicus)

Diagnosis and Staging

The diagnosis of ovarian cancer relies upon tissue biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. The initial detection of cancer is based on physical examination and imaging techniques, including ultrasound.

Physical exam

• Mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast characteristics that are particularly suspicious for ovarian cancer:
  • Nonmobile (i.e., “fixed”)
  • Nodular
  • Grossly enlarged
• Exam should include:
  • Pelvic examination
  • Rectovaginal examination
• Detection of a mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast is not indicative of malignant cancer, but should prompt imaging.

Imaging

Imaging is typically ordered 1st if signs/symptoms suggestive of a pelvic mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast are present. Discovery of concerning masses is often 1st identified on imaging and can help narrow differential diagnoses, assess the extent of disease, and assist in treatment planning. Modalities include:

• Transvaginal ultrasound Transvaginal Ultrasound Obstetric Imaging: initial imaging modality of choice
• Pelvic MRI: ↑ specificity when ultrasound findings are indeterminate
• CT of the abdomen and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy:
  • May be helpful in treatment planning
  • Generally not sensitive enough to pick up small intraperitoneal Intraperitoneal Peritoneum: Anatomy disease
• Imaging findings that are a cause of concern for malignancy Malignancy Hemothorax include:
  • Thick septa, especially if vascularized
  • Solid components
  • Wall nodularity/papillary excrescences
  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
• Additional imaging:
  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests: to detect an effusion and evaluate for metastases in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
  • Mammogram Mammogram Fibrocystic Change: should be up to date, especially in women with estrogen-producing tumors

Laboratory

Tumor Tumor Inflammation markers are generally nonspecific but can aid in diagnosis and assessing treatment response if imaging is suggestive of ovarian cancer. Commonly obtained serum tumor markers Serum Tumor Markers Serum tumor markers are proteins or carbohydrates produced by cancer cells that are associated with a malignancy of a specific origin (e.g., thyroglobulin in thyroid cancer). Genetic changes in a malignancy, such as gene mutations or patterns of gene expression, are also being used as tumor markers, and are often referred to as “cellular tumor markers.” Serum Tumor Markers include:

• CA-125 CA-125 A carbohydrate antigen that occurs in tumors of the ovary as well as in breast, kidney, and gastrointestinal tract tumors and normal tissue. While it is tumor-associated, it is not tumor-specific and may have a protective function against particles and infectious agents at mucosal surfaces. Serum Tumor Markers:
  • Associated with several ovarian tumors, especially epithelial tumors
  • Only ↑ in 50% of early-stage EOCs
  • Also ↑ in benign Benign Fibroadenoma conditions, including endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis, pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, and cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
• CA19-9 CA19-9 Sialylated lewis(a) blood group carbohydrate antigen found in many adenocarcinomas of the digestive tract, especially pancreatic tumors. Serum Tumor Markers
• Carcinoembryonic antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination ( CEA CEA A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Serum Tumor Markers)
• α-Fetoprotein ( AFP AFP The first alpha-globulins to appear in mammalian sera during fetal development and the dominant serum proteins in early embryonic life. Hepatocellular Carcinoma (HCC) and Liver Metastases): associated with germ cell tumors
• LDH LDH Osteosarcoma
• Inhibins A and B: associated with granulosa tumors
• β-hCG: ↑ in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and choriocarcinomas
• Human epididymis Epididymis The convoluted cordlike structure attached to the posterior of the testis. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of spermatozoa. Testicles: Anatomy protein 4 (HE4): a new marker associated with epithelial tumors

Histopathology and cytology

Histopathologic evaluation is ultimately required for diagnosis (gold standard).

• Histopathology determines the subtype of ovarian cancer.
• Recommended:
  • Specimen is generally obtained during the surgical excision of a concerning mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast.
  • Laparotomy Laparotomy Incision into the side of the abdomen between the ribs and pelvis. Laparotomy and Laparoscopy or laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy are both acceptable surgical techniques.
• Not recommended:
  • Fine-needle aspiration (FNA)
  • Percutaneous biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
• Pelvic washings:
  • Fill the pelvic cavity with fluid, then suction fluid → send for cytology
  • Helps identify dissemination within the cavity

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

Ovarian cancer is staged surgically. There are 4 primary stages (each also contains several substages, which are beyond the scope required for medical school).

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis procedures:

Since staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis depends on the extent of disease and presence of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis, staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis procedures involve evaluation of:

• Peritoneal cytology
• Multiple peritoneal biopsies
• Omental biopsies
• Pelvic and para-aortic lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node sampling

Ovarian cancer stages:

Individuals are staged based on their “highest” findings. For example, an individual with a tumor Tumor Inflammation confined to the ovary but with positive para-aortic lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes is classified as stage III.

Management

The primary treatment for ovarian cancer is surgery; however, specific treatment depends upon the stage of cancer. Other treatment modalities include chemotherapy Chemotherapy Osteosarcoma and immunotherapy.

Surgical management

• Surgical excision is typically the treatment of choice.
• Procedures may be conducted to remove:
  • 1 or both ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy
  • Ipsilateral or bilateral fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Para-aortic and pelvic lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes
  • Appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy (for mucinous tumors)
  • Cytoreductive (i.e., “debulking” procedures):
    • Removal of other tissues (e.g., bowel, bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, omentum Omentum Peritoneum: Anatomy) affected by the tumor Tumor Inflammation
    • The goal is to reduce the tumor Tumor Inflammation burden when complete excision is not possible.
• Pelvic washings are usually obtained 1st to help with staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis.
• Procedures typical for malignant tumors:
  • Standard procedure is total hysterectomy with BSO and lymphadenectomy.
  • Fertility-sparing procedures may be considered in young individuals depending on the situation.
• Issues for young women:
  • BSO → surgically-induced menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause → ↑ risk for early osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
  • Fertility: Egg retrieval can be considered prior to BSO.

Chemotherapy Chemotherapy Osteosarcoma

• Indicated in almost all women except in those with early stage-I disease
• Typical regimen:
  • For EOCs: Taxane-platinum combination
    • Taxanes Taxanes A group of diterpenoid cyclodecanes named for the taxanes that were discovered in the taxus tree. The action on microtubules has made some of them useful as antineoplastic agents. Microtubule and Topoisomerase Inhibitors: paclitaxel Paclitaxel A cyclodecane isolated from the bark of the pacific yew tree, taxus brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. Microtubule and Topoisomerase Inhibitors (preferred) or docetaxel Docetaxel A semisynthetic analog of paclitaxel used in the treatment of locally advanced or metastatic breast neoplasms and non-small cell lung cancer. Microtubule and Topoisomerase Inhibitors
    • Platinums: carboplatin Carboplatin An organoplatinum compound that possesses antineoplastic activity. Alkylating Agents and Platinum (preferred) or cisplatin Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These cross links appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the g2 phase of the cell cycle. Alkylating Agents and Platinum
  • For OGCTs and SCSTs: platinum-based therapy, usually bleomycin Bleomycin A complex of related glycopeptide antibiotics from streptomyces verticillus consisting of bleomycin a2 and b2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. Antitumor Antibiotics + cisplatin Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These cross links appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the g2 phase of the cell cycle. Alkylating Agents and Platinum + etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors
• Timing of administration:
  • May be given after surgery (termed adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination therapy)
  • May be given before surgery to reduce the size of a tumor Tumor Inflammation (termed neoadjuvant therapy)
  • May be used as primary treatment in individuals who are poor surgical candidates
• The exact number and timing of cycles are individualized.

Additional treatments

• Immunotherapy with monoclonal antibodies Monoclonal antibodies Antibodies produced by a single clone of cells. Ebolavirus and Marburgvirus:
  • Often used in combination with chemotherapy Chemotherapy Osteosarcoma for advanced disease
  • Example: bevacizumab Bevacizumab An anti-vegf humanized murine monoclonal antibody. It inhibits vegf receptors and helps to prevent pathologic angiogenesis. Targeted and Other Nontraditional Antineoplastic Therapy (Avastin), which binds to and inhibits vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing (VEGF)
• Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy may be considered but is rarely used in ovarian cancer.
• Psychosocial support is an important aspect of treatment. Affected individuals should be offered services to improve their quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life via counseling and social support.

Surveillance Surveillance Developmental Milestones and Normal Growth

• Regular Regular Insulin pelvic exams
• Monitor relevant tumor Tumor Inflammation markers (e.g., CA-125 CA-125 A carbohydrate antigen that occurs in tumors of the ovary as well as in breast, kidney, and gastrointestinal tract tumors and normal tissue. While it is tumor-associated, it is not tumor-specific and may have a protective function against particles and infectious agents at mucosal surfaces. Serum Tumor Markers for EOC).
• Obtain imaging for any concerns about recurrence (e.g., symptoms, ↑ tumor Tumor Inflammation markers, exam findings).
• Recurrent disease is often managed with a repeat surgical procedure and chemotherapy Chemotherapy Osteosarcoma.

Prognosis

The prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas depends primarily on the stage at diagnosis and the specific histology. General 5-year survival rates are noted in the table.

Differential Diagnosis

The differential diagnosis of a pelvic mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast includes:

• Follicular cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change (physiologic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change): As an oocyte develops in the 1st half of the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle, the follicle grows into a small cyst, approximately 2‒3 cm in size, prior to ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle. Occasionally, an oocyte may not ovulate and the follicle can enlarge (typically < 10 cm) and persist. On ultrasound, these follicles appear as simple cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change with smooth walls. The cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change typically resolve spontaneously, although large, persistent cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may be treated surgically.
• Corpus luteal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change: After ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle, the follicles transform into corpus luteal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change, secreting both estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones. On ultrasound, corpus luteal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may show slightly thicker walls and contain some internal debris. The cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may also enlarge (< 10 cm) but still usually resolve spontaneously. A corpus luteum Corpus Luteum The yellow body derived from the ruptured ovarian follicle after ovulation. The process of corpus luteum formation, luteinization, is regulated by luteinizing hormone. Ovaries: Anatomy is critical to sustaining an early pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and should not be confused with an ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy.
• Hemorrhagic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change: Follicular or corpus luteal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change bleed occasionally and are known as hemorrhagic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change. These cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change typically present with sudden-onset pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in ovulating women. On ultrasound, they appear as simple cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change with internal echoes (representing blood and clot). Hemorrhagic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change resolve spontaneously over 1‒2 menstrual cycles. Emergency surgery may be warranted to stop the bleeding if it is significant at presentation.
• Endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis: a condition in which endometrial cells implant outside the uterine cavity. Implants on the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy can grow into endometriomas or chocolate cysts Chocolate Cysts Endometriosis, which are cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change filled with endometrial fluid. Endometriomas and chocolate cysts Chocolate Cysts Endometriosis appear almost identical to hemorrhagic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change on ultrasound, but will not resolve spontaneously and must be surgically excised. Affected individuals typically present with dysmenorrhea, dyspareunia Dyspareunia Recurrent genital pain occurring during, before, or after sexual intercourse in either the male or the female. Primary Ovarian Insufficiency, and/or infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility.
• Leiomyomas ( uterine fibroids Uterine Fibroids Gynecological Imaging): common benign Benign Fibroadenoma tumors arising from smooth muscle cells in the uterine myometrium. Leiomyomas typically present with abnormal bleeding, pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and/or bulk symptoms. Fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility are identified as hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography), well-circumscribed, round masses on pelvic ultrasound and may be confused with solid adnexal masses Adnexal Masses Female Genitourinary Examination if they are pedunculated. Management is surgical if the affected individuals are symptomatic.
• Ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy: implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week of the fertilized egg ( embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week) outside the uterine cavity. Affected individuals may present with abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and/or bleeding as the developing embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week increases in size. An ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy is diagnosed by pelvic ultrasound and by monitoring β-hCG levels. Ectopic pregnancies are dangerous because a life-threatening hemorrhage may result if the fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy ruptures with the expanding pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.