Ovarian Sarcoma

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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. Primary ovarian sarcomas occur as pure sarcomas or mixed mullerian tumors (MMTs). Ovarian sarcoma is one of the least common gynecologic malignancy, constituting approximately 1% of all ovarian malignancies. Prognosis is generally poor, and the 5-year survival rate of patients with ovarian sarcoma is approximately 28.2%. 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. An elevated concentration of CA-125 in serum is seen in some patients of ovarian sarcoma. Biopsy is the study of choice. Findings on MRI suggestive of ovarian sarcoma include the following. Surgery is the mainstay of treatment for ovarian sarcoma.Among all chemotherapeutic regimens that are being used to treat ovarian sarcoma, they are divided into two groups like platinum containing regimens and non-platinum regimens. Cisplatin, carboplatin are commonly used.


Historical Perspective

There is limited information available about the historical perspective of ovarian sarcoma

Classification

  • There is no established system for the classification of ovarian Sarcoma.[1][2][3]
  • 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[4][3]
  • Clonal loss of the wild-type BRCA2 allele as well as the same somatic mutation of the TP53 gene was evident in histologic components
Types of ovarian cancer according to origin,Vargas AN. Natural history of ovarian cancer. Ecancermedicalscience. 2014;8:465. Published 2014 Sep 25. doi:10.3332/ecancer.2014.465,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176445/

Causes

The exact causes of ovarian sarcoma have not been identified.

Differentiating ovarian sarcoma 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.

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
Gynecologic
Ovarian Follicular cysts
[5] 		+/– – – – +/–
  • In US we may see a >3 cm simple cyst with no internal echo and with posterior acoustic enhancement
  • simple cyst with no internal echo or septa
  • NA
Theca lutein cysts
[6][7][8] 		+/– – – – +/–
Serous cystadenoma/carcinoma
[9][10][11][12]
  • >55 y/o
 +/– – – – +/–
  • 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
Mucinous cystadenoma/carcinoma
[13][14][15]
  • >55 y/o
 +/– – – – +/–
  • 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
Endometrioma
[16][17][18] 		+ + +/– – +
  • hyperintensity on T1-weighted images and a hypointensity on T2-weighted images
  • Powder burn hemorrhages
Teratoma
[19][20][21][22]


  • 10-30 y/o
 +/– – – – +/–
  • We may see evidence of fat components
Dysgerminoma
[23][24]
  • in the second to third decade of life
 + +/– – – +/–
  • We may see ovarian mass with septation which are hyperintense on T1 and hypo or isointense on T2 imaging
  • Sheets fried egg appearance cells
Yolk sac tumor
[25][26][27] 		+ – – – +
  • High levels of AFP
  • In US we may see a combination of echogenic and hypoechoic components
  • Yellow appearance
  • Schiller-Duval bodies (glomeruli like structures)
Fibroma
[28][29][30]
  • >50 y/o
  • Pulling sensation in the groin
 – – – +/–
  • In CT scan we may see a unilateral mass with poor contrast enhancement
  • Low signal intensity on T1 and T2
Thecoma
[31][32][33]
  • >50 y/o
 +/– – – –
Granulosa cell tumor
[34][35][36][37]
  • 50-60 y/o
 + +/– – –
Sertoli-leydig cell tumor
[38][39]
  • 15 to 35 y/o
 +/– – – – –
  • In US we may see unilateral Well-defined hypoechoic lesion
  • Low T2 signal intensity
  • areas of high signal intensity
Brenner tumor
[40][41]
  • >55 y/o
 +/– – – – – –
  • Hypointense on T2 because of fibrous content
  • Most of the times it's an accidental finding
Krukenberg tumor
[42][43]
  • >55 y/o
 +/– – +/–

Based on underlying malignancy

– –
Tubal tubo-ovarian abscess
[44][45][46][47] 		+ + – + +
  • hypointense in T1 and heterogeneous in T2
Ectopic pregnancy
[48] 		+ + +/– – +
  • NA
  • NA
Hydrosalpinx
[49][50][51]
  • NA
 + – – – +/– –
  • NA
Salpingitis
[52] 		+ + – + +
  • In US we may see , edematous and thickened endosalpingeal folds
  • NA
  • NA
Fallopian tube carcinoma
[53]
  • >60 y/o
 + + + – +/–
  • 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
  • Based on the tumor type we may have different biopsy finding
Uterine Leiomyoma
[54][55] 		+ + – – +/–
  • 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
Choriocarcinoma
[56][57][58][59] 		+ + +/– – +
  • We may see an infiltrative uterine mass and thickening of uterine wall
Leiomyosarcoma
[60][61][62][63][64]
  • >55 y/o
 + + – – +/–
  • Increased uterine size
  • Irregular central zones of low signal intensity (tumor necrosis)
Pregnancy
[65] 		+/− +/− +/− – –
  • NA
Non-gynecologic
GIT Appendiceal abscess
[66]
  • NA
 + – + +/– +
  • NA
Appendiceal neoplasm
[67][68][69][70][71] 		+ – + – +/–
  • Soft tissue mass in the appendix
  • We may see invasion to other structures
  • Gray/yellowi color
  • Cystic structures with angiolymphatic invasion

Epidemiology and Demographics

Risk Factors

There are no established risk factors for ovarian sarcoma

Screening

There is insufficient evidence to recommend routine screening for ovarian sarcoma.

Natural History, Complications, and Prognosis

  • Ovarian carcinosarcomas follow a distinct natural history compared to other more common epithelial carcinomas[77][3][78][79]
  • Ovarian carcinosarcomas are aggressive neoplasms with a predilection towards early dissemination.
  • Prognostic factors for this tumor type remain unclear because of its rarity.
  • Prognosis is generally poor, and the 5-year survival rate of patients with ovarian sarcoma is approximately 28.2%.
  • Some possible factors such as age and menopausal status have been proposed.

Diagnostic Study of Choice

  • There are no established criteria for the diagnosis of ovarian sarcoma
  • Biopsy is the study of choice

History and Symptoms

Most of the women are asymptomatic, when present, symptoms may include:[80][81][82]

  • 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 concentration of CA-125 in serum is seen in some patients of ovarian sarcoma.[83][84][85]
  • There are no diagnostic laboratory findings associated with ovarian sarcoma.

Electrocardiogram

There are no ECG findings associated with ovarian sarcoma.

X-ray

There are no x-ray findings associated with ovarian Sarcoma.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with ovarian Sarcoma.

CT scan

  • CT scan may be helpful in the diagnosis of ovarian sarcoma . Findings on CT scan suggestive of ovarian sarcoma include:[86][87][88]

MRI

  • MRI may be helpful in the diagnosis of ovarian sarcoma. Findings on MRI suggestive of ovarian sarcoma include the following:[89][86][88][90][87]

Other Imaging Findings

There are no other imaging findings associated with ovarian sarcoma

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 medical treatment for ovarian sarcoma, the mainstay of therapy is surgery and chemotherapy.

Surgery

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

Chemotherapy

  • Chemotherapy with various regimens has been used in different centers without defined conclusions on efficacy[81][82][91][92][93]
  • Multiple chemotherapeutic regimens have been evaluated with modest response rates ranging from 12% to 100%.
  • Among all chemotherapeutic regimens that are being used, they are divided into two groups like platinum containing regimens and non-platinum regimens.
    • Platinum containing chemotherapy regimens
  1. Carboplatin and ifosfamide (Carbo-I)
  2. Carboplatin (Carbo)
  3. Cyclophosphamide, adriamycin and cisplatin (CAP)
  4. Carboplatin and cyclophosphamide (Carbo-C)
  5. Epirubicin, carboplatin and 5FU (E-Carbo-F)
  6. Epirubicin, cisplatin and 5FU (ECF)
  7. Taxol and Carboplatin (T-Carbo)
  • Other chemotherapy regimens
  1. Doxorubicin (A)
  2. Doxorubicin and cyclophosphamide (AC)
  3. Cyclophosphamide (IV)
  4. Cyclophosphamide (oral)
  5. Melphalan

Primary Prevention

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

Secondary Prevention

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

References

  1. ↑ 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.
  2. ↑ Makris GM, Siristatidis C, Battista MJ, Chrelias C (2015). "Ovarian carcinosarcoma: a case report, diagnosis, treatment and literature review". Hippokratia. 19 (3): 256–9. PMC 4938474. PMID 27418786.
  3. ↑ 3.0 3.1 3.2 Rauh-Hain JA, Growdon WB, Rodriguez N, Goodman AK, Boruta DM, Schorge JO; et al. (2011). "Carcinosarcoma of the ovary: a case-control study". Gynecol Oncol. 121 (3): 477–81. doi:10.1016/j.ygyno.2011.02.023. PMID 21420726.
  4. ↑ Vargas AN (2014). "Natural history of ovarian cancer". Ecancermedicalscience. 8: 465. doi:10.3332/ecancer.2014.465. PMC 4176445. PMID 25371706.
  5. ↑ Levine D, Brown DL, Andreotti RF, Benacerraf B, Benson CB, Brewster WR, Coleman B, Depriest P, Doubilet PM, Goldstein SR, Hamper UM, Hecht JL, Horrow M, Hur HC, Marnach M, Patel MD, Platt LD, Puscheck E, Smith-Bindman R (September 2010). "Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement". Radiology. 256 (3): 943–54. doi:10.1148/radiol.10100213. PMID 20505067.
  6. ↑ Montz FJ, Schlaerth JB, Morrow CP (August 1988). "The natural history of theca lutein cysts". Obstet Gynecol. 72 (2): 247–51. PMID 2455880.
  7. ↑ Southam, Anna L. (1962). "Massive Ovarian Hyperstimulation with Clomiphene Citrate". JAMA: The Journal of the American Medical Association. 181 (5): 443. doi:10.1001/jama.1962.03050310083018b. ISSN 0098-7484.
  8. ↑ Nguyen, K T; Reid, R L; Sauerbrei, E (1986). "Antenatal sonographic detection of a fetal theca lutein cyst: a clue to maternal diabetes mellitus". Journal of Ultrasound in Medicine. 5 (11): 665–667. doi:10.7863/jum.1986.5.11.665. ISSN 0278-4297.
  9. ↑ 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.
  10. ↑ Imai, Shunsuke; Kiyozuka, Yasuhiko; Maeda, Hiroko; Noda, Tuneo; Hosick, Howard L. (1990). "Establishment and Characterization of a Human Ovarian Serous Cystadenocarcinoma Cell Line That Produces the Tumor Markers CA-125 and Tissue Polypeptide Antigen". Oncology. 47 (2): 177–184. doi:10.1159/000226813. ISSN 0030-2414.
  11. ↑ Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, Silva EG (April 2004). "Grading ovarian serous carcinoma using a two-tier system". Am. J. Surg. Pathol. 28 (4): 496–504. PMID 15087669.
  12. ↑ Li J, Fadare O, Xiang L, Kong B, Zheng W (March 2012). "Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis". J Hematol Oncol. 5: 8. doi:10.1186/1756-8722-5-8. PMID 22405464.
  13. ↑ Hoerl HD, Hart WR (December 1998). "Primary ovarian mucinous cystadenocarcinomas: a clinicopathologic study of 49 cases with long-term follow-up". Am. J. Surg. Pathol. 22 (12): 1449–62. PMID 9850171.
  14. ↑ Lee KR, Scully RE (November 2000). "Mucinous tumors of the ovary: a clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with 'pseudomyxoma peritonei'". Am. J. Surg. Pathol. 24 (11): 1447–64. PMID 11075847.
  15. ↑ 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.
  16. ↑ Mol BW, Bayram N, Lijmer JG, Wiegerinck MA, Bongers MY, van der Veen F, Bossuyt PM (December 1998). "The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis". Fertil. Steril. 70 (6): 1101–8. PMID 9848302.
  17. ↑ Kinkel, Karen; Frei, Kathrin A.; Balleyguier, Corinne; Chapron, Charles (2005). "Diagnosis of endometriosis with imaging: a review". European Radiology. 16 (2): 285–298. doi:10.1007/s00330-005-2882-y. ISSN 0938-7994.
  18. ↑ de Ziegler, Dominique; Borghese, Bruno; Chapron, Charles (2010). "Endometriosis and infertility: pathophysiology and management". The Lancet. 376 (9742): 730–738. doi:10.1016/S0140-6736(10)60490-4. ISSN 0140-6736.
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  20. ↑ Dunzendorfer, Thomas; deLAS MORENAS, ANTONIO; Kalir, Tamara; Levin, Robert M. (1999). "Struma Ovarii and Hyperthyroidism". Thyroid. 9 (5): 499–502. doi:10.1089/thy.1999.9.499. ISSN 1050-7256.
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  22. ↑ Saba, Luca; Guerriero, Stefano; Sulcis, Rosa; Virgilio, Bruna; Melis, GianBenedetto; Mallarini, Giorgio (2009). "Mature and immature ovarian teratomas: CT, US and MR imaging characteristics". European Journal of Radiology. 72 (3): 454–463. doi:10.1016/j.ejrad.2008.07.044. ISSN 0720-048X.
  23. ↑ Dgani, R.; Shoham(Schwartz), Z.; Czernobilsky, B.; Kaftori, A.; Borenstein, R.; Lancet, M. (1988). "Lactic dehydrogenase, alkaline phosphatase and human chorionic gonadotropin in a pure ovarian dysgerminoma". Gynecologic Oncology. 30 (1): 44–50. doi:10.1016/0090-8258(88)90044-3. ISSN 0090-8258.
  24. ↑ Tanaka YO, Kurosaki Y, Nishida M, Michishita N, Kuramoto K, Itai Y, Kubo T (1994). "Ovarian dysgerminoma: MR and CT appearance". J Comput Assist Tomogr. 18 (3): 443–8. PMID 8188914.
  25. ↑ Yang, Grace C.H. (2000). "Fine-needle aspiration cytology of Schiller-Duval bodies of yolk-sac tumor". Diagnostic Cytopathology. 23 (4): 228–232. doi:10.1002/1097-0339(200010)23:4<228::AID-DC2>3.0.CO;2-M. ISSN 8755-1039.
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  32. ↑ Li, Xinchun; Zhang, Weidong; Zhu, Guangbin; Sun, Congpeng; Liu, Qingyu; Shen, Yuechun (2012). "Imaging Features and Pathologic Characteristics of Ovarian Thecoma". Journal of Computer Assisted Tomography. 36 (1): 46–53. doi:10.1097/RCT.0b013e31823f6186. ISSN 0363-8715.
  33. ↑ Proctor, Francis E.; Greeley, Joseph P.; Rathmell, Thomas K. (1951). "Malignant thecoma of the ovary". American Journal of Obstetrics and Gynecology. 62 (1): 185–192. doi:10.1016/0002-9378(51)91109-X. ISSN 0002-9378.
  34. ↑ Pectasides D, Pectasides E, Psyrri A (February 2008). "Granulosa cell tumor of the ovary". Cancer Treat. Rev. 34 (1): 1–12. doi:10.1016/j.ctrv.2007.08.007. PMID 17945423.
  35. ↑ Stenwig, Jan Trygve; Hazekamp, Johan The.; Beecham, Jackson B. (1979). "Granulosa cell tumors of the ovary. A clinicopathological study of 118 cases with long-term follow-up". Gynecologic Oncology. 7 (2): 136–152. doi:10.1016/0090-8258(79)90090-8. ISSN 0090-8258.
  36. ↑ Morikawa K, Hatabu H, Togashi K, Kataoka ML, Mori T, Konishi J (1997). "Granulosa cell tumor of the ovary: MR findings". J Comput Assist Tomogr. 21 (6): 1001–4. PMID 9386298.
  37. ↑ Ko SF, Wan YL, Ng SH, Lee TY, Lin JW, Chen WJ, Kung FT, Tsai CC (May 1999). "Adult ovarian granulosa cell tumors: spectrum of sonographic and CT findings with pathologic correlation". AJR Am J Roentgenol. 172 (5): 1227–33. doi:10.2214/ajr.172.5.10227493. PMID 10227493.
  38. ↑ Lantzsch, T.; Stoerer, S.; Lawrenz, K.; Buchmann, J.; Strauss, H.-G.; Koelbl, H. (2001). "Sertoli-Leydig cell tumor". Archives of Gynecology and Obstetrics. 264 (4): 206–208. doi:10.1007/s004040000114. ISSN 0932-0067.
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  42. ↑ Kim SH, Kim WH, Park KJ, Lee JK, Kim JS (1996). "CT and MR findings of Krukenberg tumors: comparison with primary ovarian tumors". J Comput Assist Tomogr. 20 (3): 393–8. PMID 8626898.
  43. ↑ Al-Agha OM, Nicastri AD (November 2006). "An in-depth look at Krukenberg tumor: an overview". Arch. Pathol. Lab. Med. 130 (11): 1725–30. doi:10.1043/1543-2165(2006)130[1725:AILAKT]2.0.CO;2. PMID 17076540.
  44. ↑ Landers, D. V.; Sweet, R. L. (1983). "Tubo-ovarian Abscess: Contemporary Approach to Management". Clinical Infectious Diseases. 5 (5): 876–884. doi:10.1093/clinids/5.5.876. ISSN 1058-4838.
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