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.^[1]

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].

			Symptoms			Physical examination		Lab Findings	Imaging		Immunohistopathology
Diseases		Clinical manifestations						Para-clinical findings				Gold standard	Additional findings
		Age of onset	Symptoms			Physical examination		Para-clinical findings
			pelvic/abdominal pain or pressure	vaginal bleeding/discharge	GI dysturbance	Fever	Tenderness	Lab Findings	CT scan/US	MRI	Immunohistopathology
Serous cystadenoma/carcinoma ^[2]^[3]^[4]^[5]	>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 ^[6]^[7]^[8]	>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 ^[9]^[10]^[11]	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 ^[12]^[13]^[14]^[15]	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
Granulosa cell tumor ^[16]^[17]^[18]^[19]	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 ^[20]^[21]	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
Tubal	tubo-ovarian abscess ^[22]^[23]^[24]^[25]	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
	Fallopian tube carcinoma ^[26]	>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 ^[27]^[28]	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 ^[29]^[30]^[31]^[32]	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 ^[33]^[34]^[35]^[36]^[37]	>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

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.^[1]^[38]
In 2012, approximately 239,000 women were diagnosed with ovarian cancer worldwide, and 152,000 died of the disease.
Patients of all age groups may develop sarcoma of the ovary both postmenopausal and premenopausal women.
The incidence of ovarian Sarcoma increases with age; the median age at diagnosis is 50-60 years.
There is no racial predilection to ovarian Sarcoma

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:^[39]^[40]^[41]

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].

Treatment

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.

OR

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].

OR

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

OR

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

OR

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

OR

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

Surgery

Surgery is the mainstay of treatment for ovarian Sarcoma.
The management similar to that of epithelial carcinoma of ovary, consisting of cytoreductive surgery followed by adjuvant chemotherapy.

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].

OR

[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].

References

↑ ^1.0 ^1.1 Harris, M A; Delap, L M; Sengupta, P S; Wilkinson, P M; Welch, R S; Swindell, R; Shanks, J H; Wilson, G; Slade, R J; Reynolds, K; Jayson, G C (2003). "Carcinosarcoma of the ovary". British Journal of Cancer. 88 (5): 654–657. doi:10.1038/sj.bjc.6600770. ISSN 0007-0920.
↑ Jung, Seung Eun; Lee, Jae Mun; Rha, Sung Eun; Byun, Jae Young; Jung, Jung Im; Hahn, Seong Tai (2002). "CT and MR Imaging of Ovarian Tumors with Emphasis on Differential Diagnosis". RadioGraphics. 22 (6): 1305–1325. doi:10.1148/rg.226025033. ISSN 0271-5333.
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↑ McLeod, A J; Zornoza, J; Shirkhoda, A (1984). "Leiomyosarcoma: computed tomographic findings". Radiology. 152 (1): 133–136. doi:10.1148/radiology.152.1.6729102. ISSN 0033-8419.
↑ Robboy, Stanley J.; Bentley, Rex C.; Butnor, Kelly; Anderson, Malcolm C. (2000). "Pathology and Pathophysiology of Uterine Smooth-Muscle Tumors". Environmental Health Perspectives. 108: 779. doi:10.2307/3454306. ISSN 0091-6765.
↑ Ferlay, Jacques; Soerjomataram, Isabelle; Dikshit, Rajesh; Eser, Sultan; Mathers, Colin; Rebelo, Marise; Parkin, Donald Maxwell; Forman, David; Bray, Freddie (2015). "Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012". International Journal of Cancer. 136 (5): E359–E386. doi:10.1002/ijc.29210. ISSN 0020-7136.
↑ Dai Y, Shen K, Lang JH, Huang HF, Pan LY, Wu M; et al. (2011). "Primary sarcoma of the ovary: clinicopathological characteristics, prognostic factors and evaluation of therapy". Chin Med J (Engl). 124 (9): 1316–21. PMID 21740740.
↑ del Carmen MG, Birrer M, Schorge JO (2012). "Carcinosarcoma of the ovary: a review of the literature". Gynecol Oncol. 125 (1): 271–7. doi:10.1016/j.ygyno.2011.12.418. PMID 22155675.
↑ Kim HJ, Lee HM, Kim MK, Lee YK, Lee IH, Lee KH; et al. (2017). "Prognostic assessment of sarcomatous histologic subtypes of ovarian carcinosarcoma". Obstet Gynecol Sci. 60 (4): 350–356. doi:10.5468/ogs.2017.60.4.350. PMC 5547082. PMID 28791266.

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