Ovarian Sarcoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2]

Overview

Ovarian carcinosarcoma, which is also known as a malignant mixed mullerian tumor (MMMT) of the ovary, is a rare, aggressive cancer of the ovary with two distinct characteristic cancer types i.e carcinoma and sarcoma.

Historical Perspective

[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].

The association between [important risk factor/cause] and [disease name] was made in/during [year/event].

In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].

In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].

There have been several outbreaks of [disease name], including -----.

In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].

Classification

• There is no established system for the classification of ovarian Sarcoma.

• Primary ovarian sarcomas occur as pure sarcomas or mixed müllerian tumors (MMTs).
• Pure sarcomas are comprised of a single malignant mesenchymal element and are further categorized as:
  • Stromal cell sarcomas
  • Fibrosarcomas
  • Leiomyosarcomas
  • Neurofibrosarcomas
  • Rhabdomyosarcomas
  • Chondrosarcomas
  • Angiosarcomas
  • Liposarcomas
• On the other hand mixed mullerian tumors(MMTs) are defined by the presence of both carcinomatous and sarcomatous elements and are more common than pure sarcomas.
• Ovarian MMTs can be further classified as homologous or heterologous on the basis of the tissue components present.
• Homologous tumors contain elements that are native to the ovary whereas heterologous tumors contain elements that normally are not present in the ovary.

The staging of [malignancy name] is based on the [staging system].

OR

There is no established system for the staging of [malignancy name].

Pathophysiology

• The exact pathogenesis of ovarian sarcoma is not fully understood
• Clonal loss of the wild-type BRCA2 allele as well as the same somatic mutation of the TP53 gene was evident in histologic components

Causes

Disease name] may be caused by [cause1], [cause2], or [cause3].

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

Differentiating ovarian sarcoma from Other Diseases

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

Diseases		Clinical manifestations						Para-clinical findings				Gold standard	Additional findings
		Age of onset	Symptoms			Physical examination
								Lab Findings	Imaging		Immunohistopathology
			pelvic/abdominal pain or pressure	vaginal bleeding/discharge	GI dysturbance	Fever	Tenderness		CT scan/US	MRI
Serous cystadenoma/carcinoma	>55 y/o	+/–	–	–	–	+/–	Elevated levels of serum cancer antigen-125	In US we may see simple or multiloculated cyst In serous cystadenocarcinoma we may see papillary projection inside the cyst In serous cystadenocarcinoma we may see ascites	In Serous cystadenoma we may see a simple cyst with beak sign, hypointense on T1 and hyperintense on T2 In serous cystadenocarcinoma we may see some Solid malignant components inside the cyst with intermediate signal on T1 and T2	Cyst wall consist of benign/malignant Fallopian epithelial layer Psammoma body In serous cystadenocarcinoma we may see papillary projection inside the cyst	Biopsy	Most common ovarian neoplasm
Mucinous cystadenoma/carcinoma	>55 y/o	+/–	–	–	–	+/–	Elevated levels of serum cancer antigen-125	In US we may see large simple cyst with septation In mucinous cystadenocarcinoma we may see thickened internal septation with solid components inside the cyst	Stained glass appearance due to variable signal intensity on T1 and T2 The more mucin we have, there is more intensity on T1 and less intensity on T2	Cyst wall consist of columnar endocervical epithelium We may see gelatinous mucin inside the cyst	Biopsy	It may cause pseudomyxoma peritonei
Endometrioma	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	+	Iron deficiency anemia Elevated levels of serum cancer antigen-125 Increased levels of interleukin 1, chemoattractant protein-1, and interferon gamma	Complex mass on US Increased Doppler flow because of increased vascularture It may present with catamenial pneumothorax, hemothorax, and lung nodules in CT scan.	hyperintensity on T1-weighted images and a hypointensity on T2-weighted images Powder burn hemorrhages	Chocolate cyst	Laparoscopy	It may cause infertility
Teratoma	10-30 y/o	+/–	–	–	–	+/–	High level of HCG and LDH	In US we may see cystic adnexal mass with mural components and echogenic lesion due to calcification The iceberg sign Dot-dash pattern	We may see evidence of fat components	All three germ layers cell	Biopsy	It may cause ovarian torsion May content thyroid tissue and cause hyperthyroidism In plane radiography we may see calcification due to the presence of tooth in the tumor
Dysgerminoma	in the second to third decade of life	+	+/–	–	–	+/–	High level of HCG and LDH Hypercalcemia	Multilobulated solid masses	We may see ovarian mass with septation which are hyperintense on T1 and hypo or isointense on T2 imaging	Sheets fried egg appearance cells	Biopsy	Same as male seminoma
Yolk sac tumor	Young children Male infants	+	–	–	–	+	High levels of AFP	In US we may see a combination of echogenic and hypoechoic components	Ovarian mass with hemorrhagic areas	Yellow appearance Hemorrhagic Schiller-Duval bodies (glomeruli like structures)	Biopsy	The other name is ovarian endodermal sinus tumor
Fibroma	>50 y/o	Pulling sensation in the groin	–	–	–	+/–	High levels of CA-125	In CT scan we may see a unilateral mass with poor contrast enhancement	Low signal intensity on T1 and T2 We may see scattered hyperintense areas due to edema or cystic degeneration	Spindle-shaped fibroblast	Biopsy	It may cause Meigs syndrome (ovarian fibroma, ascites, and hydrothorax) It may cause ovarian torsion It may cause pleural effusion
Thecoma	>50 y/o	+/–	Postmenopausal bleeding	–	–	–	High level of estrogen	In US we may see non-specific ovarian mass We may see evidence of endometrial hyperplasia due to increased level of estrogen	Hyperintense on T2 T1 intensity depends on the amount of fibrous tissue (fibrous tissue lead to hypointensity)	Lipid-laden stromal cells with pale, vaculolated cytoplasm	Biopsy	We may see endometrial cancer as e result of hyper-estrogenism We may see ovarian fibrothecoma (mixture of fibroma and thecoma)
Granulosa cell tumor	50-60 y/o	+	Postmenopausal bleeding	+/–	–	–	High level of estrogen and progesteron We may see inhibin, calretinin, and Ki-67 on the surface of granulosa tumor cells	In US we may see solid, cystic, or multiloculated solid and cystic mass	We may see solid, cystic, or multiloculated solid and cystic mass	Call-Exner bodies	Biopsy	In postmenopausal women may cause breast tenderness
Sertoli-leydig cell tumor	15 to 35 y/o	+/–	–	–	–	–	Elevated serum testosterone level Elevated alpha-fetoprotein	In US we may see unilateral Well-defined hypoechoic lesion	Low T2 signal intensity areas of high signal intensity	Lydig cells (Polygonal pink cells with eosinophilic cytoplasm Sertoli cells (clear vacuolated cytoplasm)	Biopsy	It may cause virilization symptoms and amenorrhea
Brenner tumor	>55 y/o	+/–	–	–	–	–	–	In US we may see hypoechoic solid mass and calcification	Hypointense on T2 because of fibrous content	Yellow/pale appearance Transitional cell tumor (resembles bladder) Coffee bean nuclei on H&E	Biopsy	Most of the times it's an accidental finding
Krukenberg tumor	>55 y/o	+/–	–	+/– Based on underlying malignancy	–	–	In case of metastatic GI cancers we may see iron deficiency anemia	Mostly bilateral, complex ovarian lesion In CT scan we may see evidence of concurrent malignancy in other organs	Mostly bilateral, complex ovarian lesion with solid components Internal hyperintensity on T1 and T2 weighted MR images because of mucin Evidence of concurrent malignancy in other organs	Mucin-secreting signet cell	Imaging/ biopsy	The most common primary tumor is in colon, stomach, breast, lung, and contralateral ovary Based on underlying malignancy it may cause pleural effusion
Tubal	tubo-ovarian abscess	Young women (15-30 y/o	+	+	–	+	+	High levels of inflammatory markers Leukocytosis	In US we may see multilocular complex lesion mostly bilateral with debry inside	We may see a pelvic mass filled with fluid with thick walls hypointense in T1 and heterogeneous in T2	In abscess aspiration we may see anaerobic organisms	History/ imaging	The most common risk factors are previous PID, diabetes mellitus, intrauterine device and history of uterine surgery
	Ectopic pregnancy	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	+	High level of BhCG Progesterone level ≤5 ng/ml	In US we may see empty uterine cavity, tubal ring sign, ring of fire sign (Doppler), extra-uterine fetal heart rate	NA	NA	History/ imaging	Any women in reproductive age presenting with abdominal pain or amenorrhea should be screened for ectopic pregnancy
	Hydrosalpinx	NA	+	–	–	–	+/–	–	In US we may see tubal longitudinal folds thickening (cogwheel appearance) In CT scan we may see tubular adnexal lesion with fluid attenuation	Dilated Fallopian tube with fluid signal intensity	NA	Imaging	It is associated with endometriosis (haematosalpinx), ovulation induction, pelvic inflammatory disease, post-hysterectomy, tubal ligation, and tubal malignancy It may cause infertility
	Salpingitis	Women of reproductive age	+	+	–	+	+	Leukocytosis	In US we may see , edematous and thickened endosalpingeal folds	NA	NA	History/ physical exam	It may cause infertility
	Fallopian tube carcinoma	>60 y/o	+	+	+	–	+/–	High levels of CA125	US findings are non specific (complex mass on Fallopian tube We may see papillary projections	Low signal on T1 In case of hemorrhage inside the tumor we may see high signal intensity on T1 Low or of intermediate signal on T2 In case of serous fluid inside the tumor we may see high signal intensity on T2	Based on the tumor type we may have different biopsy finding	Biopsy	We may see Latzko triad (abdominal pain, vaginal discgarge, pelvic mass) It may cause pleural effusion
Uterine	Leiomyoma	Women of reproductive age	+	+	–	–	+/–	In chronic cases, we may see mild anemia	In US we may see hypoechoic mass with calcification and cystic areas of necrosis or degeneration may	Low to intermediate signal intensity on T1 and T2 In case of necrosis inside the mass, there might be some high signal lesions on T2	Smooth muscle	Imaging	It may cause infertility
	Choriocarcinoma	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	+	High level of B-hCG	In US we may see heterogeneous mass infiltrating myometrium Enlarged uterus Necrosis + Hemorrhage + In CT scan we may see evidence of metastasis to brain, lung and other organs	We may see an infiltrative uterine mass and thickening of uterine wall	Trophoblastic tissue origin columns and sheets of trophoblastic tissue invading uterine muscle and blood vessels	Biopsy		It is associated with bilateral theca lutein cysts Cannonball metastases to the lungs May cause hemoptysis We may see passing of grapes like tissue from the vagina
	Leiomyosarcoma	>55 y/o	+	+	–	–	+/–	In some cases we may see elevated levels of CA-125 lactate dehydrogenase	Heterogeneous mass with central low attenuation (necrosis) and calcification.	Increased uterine size Irregular central zones of low signal intensity (tumor necrosis)	We may see atypical cells, high mitotic rate, geographic areas of coagulative necrosis separated from viable neoplasm	Biopsy	In case of rapid uterine growth in post menopausal women we may suspect uterine sarcoma
	Pregnancy	Women in reproductive age (15 -45 y/o)	+/−	+/−	+/−	–	–	High level of BhCG	In US we may see ​gestational sac, yolk sac, double bleb sign and fetal pore In CT scan we may see cystic structure filled with fluid, curvilinear enhancing structure (placenta) and fetal pore	Cystic structure filled with fluid Curvilinear enhancing structure (placenta) Fetal pore	NA	History/ laboratory findings	We do not perform CT scan and MRI in pregnancy but We may unintentionally image the pregnancy with CT scan and MRI.
Non-gynecologic

OR

[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].

Epidemiology and Demographics

• Ovarian sarcoma is one of the least common gynecologic malignancy, constituting approximately 1% of all ovarian malignancies.

The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.

OR

In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

OR

In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.

• Patients of all age groups may develop sarcoma of the ovary both postmenopausal and premenopausal women.

OR

The incidence of ovarian Sarcoma increases with age; the median age at diagnosis is 50-60 years.

OR

[Disease name] commonly affects individuals younger than/older than [number of years] years of age.

OR

[Chronic disease name] is usually first diagnosed among [age group].

OR

[Acute disease name] commonly affects [age group].

There is no racial predilection to [disease name].

OR

[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

[Disease name] affects men and women equally.

OR

[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.

The majority of [disease name] cases are reported in [geographical region].

OR

[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

Risk Factors

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Natural History, Complications, and Prognosis

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

Diagnostic Study of Choice

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

There are no established criteria for the diagnosis of [disease name].

History and Symptoms

Most of the women are asymptomatic, when present, symptoms may include:

• Pain in the abdomen or pelvic area
• Bloating or swelling of the abdomen
• Quickly feeling full when eating
• Other digestive problems

Physical Examination

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Laboratory Findings

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Electrocardiogram

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

X-ray

There are no x-ray findings associated with [disease name].

OR

An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

CT scan

There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

MRI

There are no MRI findings associated with [disease name].

OR

[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Other Imaging Findings

There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

There are no other diagnostic studies associated with [disease name].

OR

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

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The mainstay of treatment for [disease name] is [therapy].

OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

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Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

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Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

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Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

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Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

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[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].