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{{CMG}}; {{AE}}{{HMHJ}}{{Hudakarman}}
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==Overview==
==Overview==
[[Ovarian cancer]] was first linked to [[Gene mutation|gene mutations]] by Dr. King who found and named [[BRCA1]] [[gene]] on [[chromosome 17]] in 1990 and [[BRCA2]] [[gene]] on [[chromosome 13]] in 1994. Ovarian epithelial tumors can be [[Classification|classified]] on several bases depending on the [[morphology]], [[Histopathology|histopathological]] behavior and clinical characteristics. The general [[classification]] of [[benign]], borderline and [[malignant]] tumors is supplemented by [[classification]] systems augmented by molecular and clinico-pathological behavior of the tumors. This section also contains [[World Health Organization|WHO]] [[classification]] of [[Ovary|ovarian]] [[Tumor|tumors]] to allow differentiation between [[Epithelium|epithelial]] tumors and other [[Ovary|ovarian]] tumors. Surface [[epithelium]] of [[Ovary|ovaries]] (OSE), once mistakenly referred as germinal [[epithelium]], consists of single layer of flat to cuboidal [[epithelial cells]]. It is characterized by [[keratin]] types found in simple [[epithelium]] and functions in exchange between [[peritoneal cavity]] and the [[Ovary|ovaries]] in addition to [[Ovary|ovarian]] cycle. During [[embryonic development]], surface [[epithelium]] of [[Ovary|ovaries]] is a part of celomic epithelium. The future surface [[epithelium]] of [[Ovary|ovaries]] then forms part of gonadal blastema and then undergoes a transformation cycle, multilayered papillary [[epithelium]] develops from simple flat to cuboidal [[epithelium]] but reverts back to simple flat to cuboidal [[epithelium]] by term. The most important functions of human surface [[epithelium]] of [[Ovary|ovaries]] are its role in transport and exchange between [[peritoneal cavity]] and [[Ovary|ovaries]], and its function in repair and rupture during [[ovulation]]. [[Ovary|Ovarian]] surface [[epithelium]] undergo epithelio-mesenchymal transformation to replace [[Ovary|ovarian]] [[stroma]] in [[Ovulation|ovulatory]] repair. The previous proposition regarding the origin of [[Epithelium|epithelial]] [[Ovarian cancer|ovarian cancers]] was that these [[Tumor|tumors]] originated from surface [[epithelium]] of the [[Ovary|ovaries]] and the [[Cancer|neoplastic]] and [[Metaplasia|metaplastic]] changes led to their differentiation into various [[Histology|histological]] subtypes such as [[serous]] [[Tumor|tumors]], clear cell carcinoma and endometrioid tumors. But apparent consistencies in this theory has led to development of alternate theories such as origin of [[Cancer|neoplastic cells]] from [[fallopian tubes]] and [[endometrium]]. Epithelial ovarian tumors' [[etiology]] is not completely understood but there are multiple [[risk factor]]<nowiki/>s that can play a role in its occurrence. The [[Theory|theories]] of the [[etiology]] of [[ovarian cancer]] suggest that repeated [[ovulation]] injures the ovarian epithelium and eventually leads to [[ovarian cancer]] development. The other [[Theory|theories]] discuss the [[origin]] of [[ovarian cancer]] that can be cortical inclusion cysts that become [[neoplastic]] or [[Metaplasia|metaplastic]] or [[Dysplasia|dysplastic]] changes of the [[fallopian tube]]. Direct effect of persistent [[Gonadotrophin]] release  from the [[pituitary gland]] on the [[ovary]] also believed to play a role in [[ovarian cancer]] [[etiology]]. On the basis of age of onset, [[vaginal discharge]], and constitutional symptoms, ovarian cancer must be differentiated from [[tubo-ovarian abscess]], [[ectopic pregnancy]], [[hydrosalpinx]], [[salpingitis]], [[fallopian tube]] [[carcinoma]], [[uterine leiomyoma]], [[choriocarcinoma]], [[leiomyosarcoma]], [[pregnancy]], [[Appendix|appendiceal]] [[abscess]], [[Appendiceal cancer|appendiceal neoplasm]], [[diverticular abscess]], [[colorectal cancer]], [[pelvic kidney]], advanced [[bladder cancer]], and [[retroperitoneal]] [[sarcoma]].
[[Ovarian cancer]] was first linked to [[Gene mutation|gene mutations]] by Dr. King who found and named [[BRCA1]] [[gene]] on [[chromosome 17]] in 1990 and [[BRCA2]] [[gene]] on [[chromosome 13]] in 1994. Ovarian epithelial tumors can be [[Classification|classified]] on several bases depending on the [[morphology]], [[Histopathology|histopathological]] behavior and clinical characteristics. The general [[classification]] of [[benign]], borderline and [[malignant]] tumors is supplemented by [[classification]] systems augmented by molecular and clinico-pathological behavior of the tumors. This section also contains [[World Health Organization|WHO]] [[classification]] of [[Ovary|ovarian]] [[Tumor|tumors]] to allow differentiation between [[Epithelium|epithelial]] tumors and other [[Ovary|ovarian]] tumors. Surface [[epithelium]] of [[Ovary|ovaries]] (OSE), once mistakenly referred as germinal [[epithelium]], consists of single layer of flat to cuboidal [[epithelial cells]]. It is characterized by [[keratin]] types found in simple [[epithelium]] and functions in exchange between [[peritoneal cavity]] and the [[Ovary|ovaries]] in addition to [[Ovary|ovarian]] cycle. During [[embryonic development]], surface [[epithelium]] of [[Ovary|ovaries]] is a part of celomic epithelium. The future surface [[epithelium]] of [[Ovary|ovaries]] then forms part of gonadal blastema and then undergoes a transformation cycle, multilayered papillary [[epithelium]] develops from simple flat to cuboidal [[epithelium]] but reverts back to simple flat to cuboidal [[epithelium]] by term. The most important functions of human surface [[epithelium]] of [[Ovary|ovaries]] are its role in transport and exchange between [[peritoneal cavity]] and [[Ovary|ovaries]], and its function in repair and rupture during [[ovulation]]. [[Ovary|Ovarian]] surface [[epithelium]] undergo epithelio-mesenchymal transformation to replace [[Ovary|ovarian]] [[stroma]] in [[Ovulation|ovulatory]] repair. The previous proposition regarding the origin of [[Epithelium|epithelial]] [[Ovarian cancer|ovarian cancers]] was that these [[Tumor|tumors]] originated from surface [[epithelium]] of the [[Ovary|ovaries]] and the [[Cancer|neoplastic]] and [[Metaplasia|metaplastic]] changes led to their differentiation into various [[Histology|histological]] subtypes such as [[serous]] [[Tumor|tumors]], clear cell carcinoma and endometrioid tumors. But apparent consistencies in this theory has led to development of alternate theories such as origin of [[Cancer|neoplastic cells]] from [[fallopian tubes]] and [[endometrium]]. Epithelial ovarian tumors' [[etiology]] is not completely understood but there are multiple [[risk factor]]<nowiki/>s that can play a role in its occurrence. The [[Theory|theories]] of the [[etiology]] of [[ovarian cancer]] suggest that repeated [[ovulation]] injures the ovarian epithelium and eventually leads to [[ovarian cancer]] development. The other [[Theory|theories]] discuss the [[origin]] of [[ovarian cancer]] that can be cortical inclusion cysts that become [[neoplastic]] or [[Metaplasia|metaplastic]] or [[Dysplasia|dysplastic]] changes of the [[fallopian tube]]. Direct effect of persistent [[Gonadotrophin]] release  from the [[pituitary gland]] on the [[ovary]] also believed to play a role in [[ovarian cancer]] [[etiology]]. On the basis of age of onset, [[vaginal discharge]], and constitutional symptoms, ovarian cancer must be differentiated from [[tubo-ovarian abscess]], [[ectopic pregnancy]], [[hydrosalpinx]], [[salpingitis]], [[fallopian tube]] [[carcinoma]], [[uterine leiomyoma]], [[choriocarcinoma]], [[leiomyosarcoma]], [[pregnancy]], [[Appendix|appendiceal]] [[abscess]], [[Appendiceal cancer|appendiceal neoplasm]], [[diverticular abscess]], [[colorectal cancer]], [[pelvic kidney]], advanced [[bladder cancer]], and [[retroperitoneal]] [[sarcoma]]. [[Ovarian cancer]] is the 7th most common type of [[cancer]] in women worldwide and the 8th most common type of [[cancer]] in the [[United States]]. [[Ovarian cancer]] is the second most common [[Gynecologic Malignancies|gynecologic malignancy]] and the most common cause of [[gynecologic cancer]] death in the [[United States]]. [[Ovarian cancer]] is the second most common gynecologic malignancy in developed countries, with an incidence of 9.4 per 100,000 women and a mortality rate of 5.1 per 100,000. In developing countries, it is the third most common gynecologic malignancy (cervical cancer is the most common), with an incidence of 5.0 per 100,000 and a mortality rate of 3.1 per 100,000. The age-adjusted [[prevalence]] of [[ovarian cancer]] in the [[United States]] is 71.3 per 100,000 in 2011. The estimated number of new cases of [[ovarian cancer]] is approximately 22,000. Epithelial ovarian tumors can have multiple [[Risk factor|risk factors]]. [[Genetics|Genetic]] [[Risk factor|risk factors]] constitute a major proportion of all the associated [[Risk factor|risk factors]]. There are no recommendations for [[screening]] [[ovarian cancer]] in asymptomatic women although better outcome is associated with early [[diagnosis]]. [[Biomarkers]] from [[peritoneal fluid]] can be used as a mean of early detection of [[ovarian cancer]] but this is still an emerging proof. Examples of [[screening]] and [[diagnostic]] methods for [[ovarian cancer]] include [[pelvic examination]], [[CA125|cancer antigen 125]] ([[CA125]]) [[tumor marker]], [[transvaginal ultrasound]] (TVU), multimarker panels, and bioinformatic analysis of proteomic patterns. [[Ovarian cancer]] is often diagnosed late resulting in a poor overall outcome for the patient. Ovarian cancer complications can be spread of cancer to other organs, progressive function loss of various organs, ascites (fluid in the abdomen), intestinal obstruction. Ovarian cancer has a poor [[prognosis]]. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries. The clinical presentation of epithelial ovarian tumors depends on the type of the [[tumor]] involved. The natural history can vary depending upon the type of [[tumor]] and the time at [[diagnosis]]. Ovarian cancer complications can be spread of cancer to other organs, progressive function loss of various organs, ascites (fluid in the abdomen), intestinal obstruction. Ovarian cancer has a poor [[prognosis]]. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries. [[Histology]] of the excised [[tumor]] after [[surgery]] is the [[Gold standard (test)|gold standard]] test for the [[diagnosis]] of [[ovarian]] [[Tumor|tumors]]. [[Surgery]] must be performed when the patient presents with an [[adnexal]] [[mass]] in the [[abdominal]]/[[pelvic]] [[Physical examination|exam]] and elevated serum concentration of associated [[tumor markers]]. Some may be [[Diagnosis|diagnosed]] using [[Ultrasound|ultrasonographic imaging]]. However, the [[tumor]] should be removed [[Surgery|surgically]]. The [[clinical]] manifestations of patients with epithelial ovarian tumors depend on the type of the [[tumor]] and its potential to produce [[hormonal]] materials. Usually, they present with  [[abdominal pain]] or [[Abdominal distention|distention]], [[menstrual irregularities]], symptoms of [[virilization]], rapidly growing [[abdominal]]/[[pelvic]] [[mass]], [[acute abdominal pain]] from [[complications]] such as [[necrosis]], [[Capsule|capsular]] distention, [[rupture]] or [[torsion]] and or simply they can be [[asymptomatic]]. Patients with epithelial tumors of the [[ovary]] usually appear normal. [[Physical examination]] of these patients is usually unremarkable and the [[tumors]] tend to be discovered incidentally or during [[imaging]] workups for another reason. When [[symptomatic]], the [[physical examination]] may be remarkable for [[Abdominal]]/[[pelvic]] [[mass]] and/or [[signs]] of [[virilization]], [[precocious puberty]], and [[pregnancy]] depending on the capacity of the [[tumor]] for the production of [[hormones]]. The evaluation includes [[laboratory]] work, [[imaging]] and [[surgical]] exploration for the definite [[diagnosis]]. Routine lab work includes CBC and CMP, Serum biomarkers of of [[epithelial ovarian cancer]] includes [[CA125]], HE4, OVA1. Serum biomarkers of the germ cell and sex cord-stromal ovarian cancer include [[alpha-fetoprotein]], [[human chorionic gonadotropin]], [[lactate dehydrogenase]], [[estradiol]], [[Inhibin]], [[testosterone]], [[androstenedione]], dehydroepiandrostenedione, [[anti-Müllerian hormone]]. There are no [[ECG]] findings associated with epithelial [[ovarian]] [[tumor]]. There are no specific x-ray findings associated with epithelial ovarian tumors. [[Ultrasound]] is the most frequently used [[modality]] for the [[diagnosis]]. On [[Ultrasound]] imaging, epithelial ovarian tumors may have [[Variable-order Markov model|variable]] appearances. [[CT scan]] of the [[pelvis]], [[abdomen]], and [[chest]] can be helpful as one of the evaluating tools of Epithelial ovarian tumors and the tumor extension and [[metastasis]]. [[CT scan]] can be used for [[Preoperative assessment|preoperative]] [[staging]] to look for [[lymphadenopathy]], [[peritoneal]], and distant [[metastases]]. [[MRI]] of the [[pelvis]], [[abdomen]], and [[chest]] can be helpful as one of the evaluating tools of epithelial ovarian tumors. There are no other imaging findings associated with epithelial ovarian tumors. There are no other diagnostic studies associated with epithelial ovarian tumors. Medical therapies, such as [[chemotherapy]] and [[radiation]], are often employed post-surgical therapy as a means to treat residual disease. The success of medical therapy often hinges on the [[histology]] of the [[tumor]]. [[Surgical]] [[intervention]] is the mainstay of management of epithelial ovarian tumors. [[Surgery]] must be done for the purpose of [[Cancer staging|staging]] and maybe treatment according to the stage of the tumor. [[Surgical]] management of the epithelial ovarian tumors, for the purpose of treatment, classified to two categories according to the preference of the patient to preserve the [[ovary]] or not. There are no established measures for the [[Prevention (medical)|primary prevention]] of epithelial ovarian tumors. There are no established measures for the [[Prevention (medical)|secondary prevention]] of epithelial ovarian tumors.
 


==Historical Perspective==
==Historical Perspective==
Line 20: Line 21:
On the basis of age of onset, [[vaginal discharge]], and constitutional symptoms, ovarian cancer must be differentiated from [[tubo-ovarian abscess]], [[ectopic pregnancy]], [[hydrosalpinx]], [[salpingitis]], [[fallopian tube]] [[carcinoma]], [[uterine leiomyoma]], [[choriocarcinoma]], [[leiomyosarcoma]], [[pregnancy]], [[Appendix|appendiceal]] [[abscess]], [[Appendiceal cancer|appendiceal neoplasm]], [[diverticular abscess]], [[colorectal cancer]], [[pelvic kidney]], advanced [[bladder cancer]], and [[retroperitoneal]] [[sarcoma]].
On the basis of age of onset, [[vaginal discharge]], and constitutional symptoms, ovarian cancer must be differentiated from [[tubo-ovarian abscess]], [[ectopic pregnancy]], [[hydrosalpinx]], [[salpingitis]], [[fallopian tube]] [[carcinoma]], [[uterine leiomyoma]], [[choriocarcinoma]], [[leiomyosarcoma]], [[pregnancy]], [[Appendix|appendiceal]] [[abscess]], [[Appendiceal cancer|appendiceal neoplasm]], [[diverticular abscess]], [[colorectal cancer]], [[pelvic kidney]], advanced [[bladder cancer]], and [[retroperitoneal]] [[sarcoma]].
==Epidemiology and Demographics==
==Epidemiology and Demographics==
[[Ovarian cancer]] is the 7th most common type of [[cancer]] in women worldwide and the 8th most common type of [[cancer]] in the [[United States]]. [[Ovarian cancer]] is the second most common [[Gynecologic Malignancies|gynecologic malignancy]] and the most common cause of [[gynecologic cancer]] death in the [[United States]]. [[Ovarian cancer]] is the second most common gynecologic malignancy in developed countries, with an incidence of 9.4 per 100,000 women and a mortality rate of 5.1 per 100,000. In developing countries, it is the third most common gynecologic malignancy (cervical cancer is the most common), with an incidence of 5.0 per 100,000 and a mortality rate of 3.1 per 100,000. The age-adjusted [[prevalence]] of [[ovarian cancer]] in the [[United States]] is 71.3 per 100,000 in 2011. The estimated number of new cases of [[ovarian cancer]] is approximately 22,000.


==Risk Factors==
==Risk Factors==
Epithelial ovarian tumors can have multiple [[Risk factor|risk factors]]. [[Genetics|Genetic]] [[Risk factor|risk factors]] constitute a major proportion of all the associated [[Risk factor|risk factors]].


==Screening==
==Screening==
There are no recommendations for [[screening]] epithelial ovarian tumors in asymptomatic women although better outcome is associated with early [[diagnosis]]. [[Biomarkers]] from [[peritoneal fluid]] can be used as a mean of early detection of [[ovarian cancer]] but this is still an emerging proof. Examples of [[screening]] and [[diagnostic]] methods for [[ovarian cancer]] include [[pelvic examination]], [[CA125|cancer antigen 125]] ([[CA125]]) [[tumor marker]], [[transvaginal ultrasound]] (TVU), multimarker panels, and bioinformatic analysis of proteomic patterns.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==


 
The clinical presentation of epithelial ovarian tumors depends on the type of the [[tumor]] involved. The natural history can vary depending upon the type of [[tumor]] and the time at [[diagnosis]]. Ovarian cancer complications can be spread of cancer to other organs, progressive function loss of various organs, ascites (fluid in the abdomen), intestinal obstruction. Ovarian cancer has a poor [[prognosis]]. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries.
==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===
[[Histology]] of the excised [[tumor]] after [[surgery]] is the [[Gold standard (test)|gold standard]] test for the [[diagnosis]] of [[ovarian]] [[Tumor|tumors]]. [[Surgery]] must be performed when the patient presents with an [[adnexal]] [[mass]] in the [[abdominal]]/[[pelvic]] [[Physical examination|exam]] and elevated serum concentration of associated [[tumor markers]]. Some may be [[Diagnosis|diagnosed]] using [[Ultrasound|ultrasonographic imaging]]. However, the [[tumor]] should be removed [[Surgery|surgically]].


===History and Symptoms===
===History and Symptoms===
The [[clinical]] manifestations of patients with epithelial ovarian tumors depend on the type of the [[tumor]] and its potential to produce [[hormonal]] materials. Usually, they present with  [[abdominal pain]] or [[Abdominal distention|distention]], [[menstrual irregularities]], symptoms of [[virilization]], rapidly growing [[abdominal]]/[[pelvic]] [[mass]], [[acute abdominal pain]] from [[complications]] such as [[necrosis]], [[Capsule|capsular]] distention, [[rupture]] or [[torsion]] and or simply they can be [[asymptomatic]].  


===Physical Examination===
===Physical Examination===
Patients with epithelial tumors of the [[ovary]] usually appear normal. [[Physical examination]] of these patients is usually unremarkable and the [[tumors]] tend to be discovered incidentally or during [[imaging]] workups for another reason. When [[symptomatic]], the [[physical examination]] may be remarkable for [[Abdominal]]/[[pelvic]] [[mass]] and/or [[signs]] of [[virilization]], [[precocious puberty]], and [[pregnancy]] depending on the capacity of the [[tumor]] for the production of [[hormones]].


===Laboratory Findings===
===Laboratory Findings===
The evaluation includes [[laboratory]] work, [[imaging]] and [[surgical]] exploration for the definite [[diagnosis]]. Routine lab work includes CBC and CMP, Serum biomarkers of of [[epithelial ovarian cancer]] includes [[CA125]], HE4, OVA1. Serum biomarkers of the germ cell and sex cord-stromal ovarian cancer include [[alpha-fetoprotein]], [[human chorionic gonadotropin]], [[lactate dehydrogenase]], [[estradiol]], [[Inhibin]], [[testosterone]], [[androstenedione]], dehydroepiandrostenedione, [[anti-Müllerian hormone]].


===Electrocardiogram===
===Electrocardiogram===
There are no [[ECG]] findings associated with epithelial [[ovarian]] [[tumor]].


===X-ray===
===X-ray===
There are no specific x-ray findings associated with epithelial ovarian tumors.


===Echocardiography and Ultrasound===
===Echocardiography and Ultrasound===
[[Ultrasound]] is the most frequently used [[modality]] for the [[diagnosis]]. On [[Ultrasound]] imaging, epithelial ovarian tumors may have [[Variable-order Markov model|variable]] appearances.


===CT scan===
===CT scan===
[[CT scan]] of the [[pelvis]], [[abdomen]], and [[chest]] can be helpful as one of the evaluating tools of Epithelial ovarian tumors and the tumor extension and [[metastasis]]. [[CT scan]] can be used for [[Preoperative assessment|preoperative]] [[staging]] to look for [[lymphadenopathy]], [[peritoneal]], and distant [[metastases]].


===MRI===
===MRI===
[[MRI]] of the [[pelvis]], [[abdomen]], and [[chest]] can be helpful as one of the evaluating tools of epithelial ovarian tumors.


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with epithelial ovarian tumors.


===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with epithelial ovarian tumors.


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
 
Medical therapies, such as [[chemotherapy]] and [[radiation]], are often employed post-surgical therapy as a means to treat residual disease. The success of medical therapy often hinges on the [[histology]] of the [[tumor]].
=== Interventions ===


===Surgery===
===Surgery===
[[Surgical]] [[intervention]] is the mainstay of management of epithelial ovarian tumors. [[Surgery]] must be done for the purpose of [[Cancer staging|staging]] and maybe treatment according to the stage of the tumor. [[Surgical]] management of the epithelial ovarian tumors, for the purpose of treatment, classified to two categories according to the preference of the patient to preserve the [[ovary]] or not.


===Primary Prevention===
===Primary Prevention===
There are no established measures for the [[Prevention (medical)|primary prevention]] of epithelial ovarian tumors.


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the [[Prevention (medical)|secondary prevention]] of epithelial ovarian tumors.


==References==
==References==

Latest revision as of 19:50, 14 October 2019

Epithelial ovarian tumors Microchapters

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Overview

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Differentiating Epithelial Ovarian Tumors from other Diseases

Epidemiology and Demographics

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Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]Huda A. Karman, M.D.

Overview

Ovarian cancer was first linked to gene mutations by Dr. King who found and named BRCA1 gene on chromosome 17 in 1990 and BRCA2 gene on chromosome 13 in 1994. Ovarian epithelial tumors can be classified on several bases depending on the morphology, histopathological behavior and clinical characteristics. The general classification of benign, borderline and malignant tumors is supplemented by classification systems augmented by molecular and clinico-pathological behavior of the tumors. This section also contains WHO classification of ovarian tumors to allow differentiation between epithelial tumors and other ovarian tumors. Surface epithelium of ovaries (OSE), once mistakenly referred as germinal epithelium, consists of single layer of flat to cuboidal epithelial cells. It is characterized by keratin types found in simple epithelium and functions in exchange between peritoneal cavity and the ovaries in addition to ovarian cycle. During embryonic development, surface epithelium of ovaries is a part of celomic epithelium. The future surface epithelium of ovaries then forms part of gonadal blastema and then undergoes a transformation cycle, multilayered papillary epithelium develops from simple flat to cuboidal epithelium but reverts back to simple flat to cuboidal epithelium by term. The most important functions of human surface epithelium of ovaries are its role in transport and exchange between peritoneal cavity and ovaries, and its function in repair and rupture during ovulation. Ovarian surface epithelium undergo epithelio-mesenchymal transformation to replace ovarian stroma in ovulatory repair. The previous proposition regarding the origin of epithelial ovarian cancers was that these tumors originated from surface epithelium of the ovaries and the neoplastic and metaplastic changes led to their differentiation into various histological subtypes such as serous tumors, clear cell carcinoma and endometrioid tumors. But apparent consistencies in this theory has led to development of alternate theories such as origin of neoplastic cells from fallopian tubes and endometrium. Epithelial ovarian tumors' etiology is not completely understood but there are multiple risk factors that can play a role in its occurrence. The theories of the etiology of ovarian cancer suggest that repeated ovulation injures the ovarian epithelium and eventually leads to ovarian cancer development. The other theories discuss the origin of ovarian cancer that can be cortical inclusion cysts that become neoplastic or metaplastic or dysplastic changes of the fallopian tube. Direct effect of persistent Gonadotrophin release from the pituitary gland on the ovary also believed to play a role in ovarian cancer etiology. On the basis of age of onset, vaginal discharge, and constitutional symptoms, ovarian cancer must be differentiated from tubo-ovarian abscess, ectopic pregnancy, hydrosalpinx, salpingitis, fallopian tube carcinoma, uterine leiomyoma, choriocarcinoma, leiomyosarcoma, pregnancy, appendiceal abscess, appendiceal neoplasm, diverticular abscess, colorectal cancer, pelvic kidney, advanced bladder cancer, and retroperitoneal sarcoma. Ovarian cancer is the 7th most common type of cancer in women worldwide and the 8th most common type of cancer in the United States. Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer death in the United States. Ovarian cancer is the second most common gynecologic malignancy in developed countries, with an incidence of 9.4 per 100,000 women and a mortality rate of 5.1 per 100,000. In developing countries, it is the third most common gynecologic malignancy (cervical cancer is the most common), with an incidence of 5.0 per 100,000 and a mortality rate of 3.1 per 100,000. The age-adjusted prevalence of ovarian cancer in the United States is 71.3 per 100,000 in 2011. The estimated number of new cases of ovarian cancer is approximately 22,000. Epithelial ovarian tumors can have multiple risk factors. Genetic risk factors constitute a major proportion of all the associated risk factors. There are no recommendations for screening ovarian cancer in asymptomatic women although better outcome is associated with early diagnosis. Biomarkers from peritoneal fluid can be used as a mean of early detection of ovarian cancer but this is still an emerging proof. Examples of screening and diagnostic methods for ovarian cancer include pelvic examination, cancer antigen 125 (CA125) tumor marker, transvaginal ultrasound (TVU), multimarker panels, and bioinformatic analysis of proteomic patterns. Ovarian cancer is often diagnosed late resulting in a poor overall outcome for the patient. Ovarian cancer complications can be spread of cancer to other organs, progressive function loss of various organs, ascites (fluid in the abdomen), intestinal obstruction. Ovarian cancer has a poor prognosis. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries. The clinical presentation of epithelial ovarian tumors depends on the type of the tumor involved. The natural history can vary depending upon the type of tumor and the time at diagnosis. Ovarian cancer complications can be spread of cancer to other organs, progressive function loss of various organs, ascites (fluid in the abdomen), intestinal obstruction. Ovarian cancer has a poor prognosis. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries. Histology of the excised tumor after surgery is the gold standard test for the diagnosis of ovarian tumors. Surgery must be performed when the patient presents with an adnexal mass in the abdominal/pelvic exam and elevated serum concentration of associated tumor markers. Some may be diagnosed using ultrasonographic imaging. However, the tumor should be removed surgically. The clinical manifestations of patients with epithelial ovarian tumors depend on the type of the tumor and its potential to produce hormonal materials. Usually, they present with abdominal pain or distention, menstrual irregularities, symptoms of virilization, rapidly growing abdominal/pelvic mass, acute abdominal pain from complications such as necrosis, capsular distention, rupture or torsion and or simply they can be asymptomatic. Patients with epithelial tumors of the ovary usually appear normal. Physical examination of these patients is usually unremarkable and the tumors tend to be discovered incidentally or during imaging workups for another reason. When symptomatic, the physical examination may be remarkable for Abdominal/pelvic mass and/or signs of virilization, precocious puberty, and pregnancy depending on the capacity of the tumor for the production of hormones. The evaluation includes laboratory work, imaging and surgical exploration for the definite diagnosis. Routine lab work includes CBC and CMP, Serum biomarkers of of epithelial ovarian cancer includes CA125, HE4, OVA1. Serum biomarkers of the germ cell and sex cord-stromal ovarian cancer include alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, estradiol, Inhibin, testosterone, androstenedione, dehydroepiandrostenedione, anti-Müllerian hormone. There are no ECG findings associated with epithelial ovarian tumor. There are no specific x-ray findings associated with epithelial ovarian tumors. Ultrasound is the most frequently used modality for the diagnosis. On Ultrasound imaging, epithelial ovarian tumors may have variable appearances. CT scan of the pelvis, abdomen, and chest can be helpful as one of the evaluating tools of Epithelial ovarian tumors and the tumor extension and metastasis. CT scan can be used for preoperative staging to look for lymphadenopathy, peritoneal, and distant metastases. MRI of the pelvis, abdomen, and chest can be helpful as one of the evaluating tools of epithelial ovarian tumors. There are no other imaging findings associated with epithelial ovarian tumors. There are no other diagnostic studies associated with epithelial ovarian tumors. Medical therapies, such as chemotherapy and radiation, are often employed post-surgical therapy as a means to treat residual disease. The success of medical therapy often hinges on the histology of the tumor. Surgical intervention is the mainstay of management of epithelial ovarian tumors. Surgery must be done for the purpose of staging and maybe treatment according to the stage of the tumor. Surgical management of the epithelial ovarian tumors, for the purpose of treatment, classified to two categories according to the preference of the patient to preserve the ovary or not. There are no established measures for the primary prevention of epithelial ovarian tumors. There are no established measures for the secondary prevention of epithelial ovarian tumors.


Historical Perspective

Ovarian cancer was first linked to gene mutations by Dr. King who found and named BRCA1 gene on chromosome 17 in 1990 and BRCA2 gene on chromosome 13 in 1994.

Classification

Ovarian epithelial tumors can be classified on several bases depending on the morphology, histopathological behavior and clinical characteristics. The general classification of benign, borderline and malignant tumors is supplemented by classification systems augmented by molecular and clinico-pathological behavior of the tumors. This section also contains WHO classification of ovarian tumors to allow differentiation between epithelial tumors and other ovarian tumors.

Pathophysiology

Surface epithelium of ovaries (OSE), once mistakenly referred as germinal epithelium, consists of single layer of flat to cuboidal epithelial cells. It is characterized by keratin types found in simple epithelium and functions in exchange between peritoneal cavity and the ovaries in addition to ovarian cycle. During embryonic development, surface epithelium of ovaries is a part of celomic epithelium. The future surface epithelium of ovaries then forms part of gonadal blastema and then undergoes a transformation cycle, multilayered papillary epithelium develops from simple flat to cuboidal epithelium but reverts back to simple flat to cuboidal epithelium by term. The most important functions of human surface epithelium of ovaries are its role in transport and exchange between peritoneal cavity and ovaries, and its function in repair and rupture during ovulation. Ovarian surface epithelium undergo epithelio-mesenchymal transformation to replace ovarian stroma in ovulatory repair. The previous proposition regarding the origin of epithelial ovarian cancers was that these tumors originated from surface epithelium of the ovaries and the neoplastic and metaplastic changes led to their differentiation into various histological subtypes such as serous tumors, clear cell carcinoma and endometrioid tumors. But apparent consistencies in this theory has led to development of alternate theories such as origin of neoplastic cells from fallopian tubes and endometrium.

Causes

Epithelial ovarian tumors' etiology is not completely understood but there are multiple risk factors that can play a role in its occurrence. The theories of the etiology of ovarian cancer suggest that repeated ovulation injures the ovarian epithelium and eventually leads to ovarian cancer development. The other theories discuss the origin of ovarian cancer that can be cortical inclusion cysts that become neoplastic or metaplastic or dysplastic changes of the fallopian tube. Direct effect of persistent Gonadotrophin release from the pituitary gland on the ovary also believed to play a role in ovarian cancer etiology.

Differentiating Epithelial Ovarian Tumors from Other Diseases

On the basis of age of onset, vaginal discharge, and constitutional symptoms, ovarian cancer must be differentiated from tubo-ovarian abscess, ectopic pregnancy, hydrosalpinx, salpingitis, fallopian tube carcinoma, uterine leiomyoma, choriocarcinoma, leiomyosarcoma, pregnancy, appendiceal abscess, appendiceal neoplasm, diverticular abscess, colorectal cancer, pelvic kidney, advanced bladder cancer, and retroperitoneal sarcoma.

Epidemiology and Demographics

Ovarian cancer is the 7th most common type of cancer in women worldwide and the 8th most common type of cancer in the United States. Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer death in the United States. Ovarian cancer is the second most common gynecologic malignancy in developed countries, with an incidence of 9.4 per 100,000 women and a mortality rate of 5.1 per 100,000. In developing countries, it is the third most common gynecologic malignancy (cervical cancer is the most common), with an incidence of 5.0 per 100,000 and a mortality rate of 3.1 per 100,000. The age-adjusted prevalence of ovarian cancer in the United States is 71.3 per 100,000 in 2011. The estimated number of new cases of ovarian cancer is approximately 22,000.

Risk Factors

Epithelial ovarian tumors can have multiple risk factors. Genetic risk factors constitute a major proportion of all the associated risk factors.

Screening

There are no recommendations for screening epithelial ovarian tumors in asymptomatic women although better outcome is associated with early diagnosis. Biomarkers from peritoneal fluid can be used as a mean of early detection of ovarian cancer but this is still an emerging proof. Examples of screening and diagnostic methods for ovarian cancer include pelvic examination, cancer antigen 125 (CA125) tumor marker, transvaginal ultrasound (TVU), multimarker panels, and bioinformatic analysis of proteomic patterns.

Natural History, Complications, and Prognosis

The clinical presentation of epithelial ovarian tumors depends on the type of the tumor involved. The natural history can vary depending upon the type of tumor and the time at diagnosis. Ovarian cancer complications can be spread of cancer to other organs, progressive function loss of various organs, ascites (fluid in the abdomen), intestinal obstruction. Ovarian cancer has a poor prognosis. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries.

Diagnosis

Diagnostic Study of Choice

Histology of the excised tumor after surgery is the gold standard test for the diagnosis of ovarian tumors. Surgery must be performed when the patient presents with an adnexal mass in the abdominal/pelvic exam and elevated serum concentration of associated tumor markers. Some may be diagnosed using ultrasonographic imaging. However, the tumor should be removed surgically.

History and Symptoms

The clinical manifestations of patients with epithelial ovarian tumors depend on the type of the tumor and its potential to produce hormonal materials. Usually, they present with abdominal pain or distention, menstrual irregularities, symptoms of virilization, rapidly growing abdominal/pelvic mass, acute abdominal pain from complications such as necrosis, capsular distention, rupture or torsion and or simply they can be asymptomatic.  

Physical Examination

Patients with epithelial tumors of the ovary usually appear normal. Physical examination of these patients is usually unremarkable and the tumors tend to be discovered incidentally or during imaging workups for another reason. When symptomatic, the physical examination may be remarkable for Abdominal/pelvic mass and/or signs of virilization, precocious puberty, and pregnancy depending on the capacity of the tumor for the production of hormones.

Laboratory Findings

The evaluation includes laboratory work, imaging and surgical exploration for the definite diagnosis. Routine lab work includes CBC and CMP, Serum biomarkers of of epithelial ovarian cancer includes CA125, HE4, OVA1. Serum biomarkers of the germ cell and sex cord-stromal ovarian cancer include alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, estradiol, Inhibin, testosterone, androstenedione, dehydroepiandrostenedione, anti-Müllerian hormone.

Electrocardiogram

There are no ECG findings associated with epithelial ovarian tumor.

X-ray

There are no specific x-ray findings associated with epithelial ovarian tumors.

Echocardiography and Ultrasound

Ultrasound is the most frequently used modality for the diagnosis. On Ultrasound imaging, epithelial ovarian tumors may have variable appearances.

CT scan

CT scan of the pelvis, abdomen, and chest can be helpful as one of the evaluating tools of Epithelial ovarian tumors and the tumor extension and metastasis. CT scan can be used for preoperative staging to look for lymphadenopathy, peritoneal, and distant metastases.

MRI

MRI of the pelvis, abdomen, and chest can be helpful as one of the evaluating tools of epithelial ovarian tumors.

Other Imaging Findings

There are no other imaging findings associated with epithelial ovarian tumors.

Other Diagnostic Studies

There are no other diagnostic studies associated with epithelial ovarian tumors.

Treatment

Medical Therapy

Medical therapies, such as chemotherapy and radiation, are often employed post-surgical therapy as a means to treat residual disease. The success of medical therapy often hinges on the histology of the tumor.

Surgery

Surgical intervention is the mainstay of management of epithelial ovarian tumors. Surgery must be done for the purpose of staging and maybe treatment according to the stage of the tumor. Surgical management of the epithelial ovarian tumors, for the purpose of treatment, classified to two categories according to the preference of the patient to preserve the ovary or not.

Primary Prevention

There are no established measures for the primary prevention of epithelial ovarian tumors.

Secondary Prevention

There are no established measures for the secondary prevention of epithelial ovarian tumors.

References