Gestational trophoblastic neoplasia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Monalisa Dmello, M.B,B.S., M.D. [3]

Overview

Gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental-site trophoblastic tumor [PSTT] and epitheloid trophoblastic tumor [ETT]) should be differentiated from other conditions presenting with similar symptoms and signs such as increase in uterine size, vaginal bleeding and amenorrhea. The differentials include molar pregnancy (complete and partial moles), ovarian tumors, spontaneous abortion, ectopic pregnancy and normal term pregnancy.

Differentiating Choriocarcinoma From Other Diseases

Gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental-site trophoblastic tumor [PSTT] and epitheloid trophoblastic tumor [ETT]) should be differentiated from other conditions presenting with similar symptoms and signs such as increase in uterine size, vaginal bleeding and amenorrhea. The differentials include the following:

Differential Diagnosis Clinical Features Karyotype Immunostaining Management
Presenting Complaints Potential for Neoplastic Conversion Beta Human Chorionic Gonadotropin (Beta-hCG) Baseline Levels History of Pregnancy Theca Leutin Cysts Metastatic Route Cytokeratin 18 HLA-G Human Chorionic Gonadotropin (hCG) Transformation-Related Protein 63 (P63) Human Placental Lactogen (hPL) Melanoma Cell Adhesion Molecule (Mel-CAM) Ki67
Complete Hydatidiform Mole[1][2][3]
  • High rate of progression (15-20%)
  • Extremely high levels
    • >100000 mIU/ml in half of the patients
  • Not related
  • Present
  • 46, XX or 46 XY (Paternal dispermy)
  • Negative
  • Negative
  • Extremely elevated
  • Absent
  • Absent
  • Absent
  • Absent
  • Dilation and curettage (suction)
Partial Hydatidiform Mole[4][5][6]
  • < 5 % progression rate
  • Highly elevated
    • >100000 mIU/ml in one in ten patients
  • Not related
  • Absent
  • 69,XXY or XYY
  • Negative
  • Negative
  • Highly elevated
  • Absent
  • Absent
  • Absent
  • Absent
  • Dilation and curettage (suction)
Invasive Molar Pregnancy
  • High
  • May be present
  • Hematogenous
  • 69,XXY or XYY
  • Positive
  • Positive
  • Highly elevated
  • Absent
  • Absent
  • Absent
  • Absent
Choriocarcinoma[7][8][9]
  • High
  • Present
  • Hematogenous
  • Positive
  • Positive
  • Highly elevated
  • Positive
Placental-site Trophoblastic tumor (PSTT) and Epitheloid Trophoblastic Tumor (ETT)[10][11][12][13]
  • Neoplastic
  • Moderatley elevated
    • <1000 mIU/ml in majority of patients
  • Absent
  • 46,XX or XY
  • Positive
  • Positive
  • Negative (Positive in ETT)
  • Positive (Negative in ETT)
  • Positive (Negative in ETT)
  • Positive ( >1% in PSTT and >10% in ETT)
  • Hysterectomy
Ovarian Tumors[14][15][16][17][18][19][20][21][22]
  • Overall incidence in pregnancy is 2.4-5.7% (1/300 to 1/556 pregnancies)
  • Incidence of malignancy is 1/15,000 to 1/32,000 pregnancies
  • Germ cell and epithelial tumors are most common
  • Absent
  • Direct extension or seeding
  • Negative (Epithelial tumors may be positive for cytokeratin AE1/AE3)
  • Positive
  • Positive (especially in epithelial cancers)
  • Positive
  • Positive
  • Positive
  • Surgical debulking
  • Intravenous/intraperitoneal chemotherapy
Spontaneous Abortion[23][24]
  • Not applicable
  • Decline in levels within 24 hours
  • Absent
  • Not applicable
  • Negative
  • Negative
  • Progressive decline
  • Negative
  • Negative
  • Negative
  • Negative
  • Uterine evacuation if patient has sepsis, hemorrhage and/or intractable pain
  • Medical management using prostaglandin analogs
  • Expectant management if no complications
Ectopic Pregnancy[25][26]
  • Not applicable
  • Failure of hCG doubling (especially during the first 8 weeks)
  • Absent
  • Not applicable
  • Negative
  • Negative
  • A rising β-hCG concentration that fails to reach 50% or plateaus
  • Negative
  • Negative
  • Negative
  • Negative
  • Expectant management (Failure of transvaginal ultrasonography to show the location of the gestational sac and the serum levels of β-hCG and progesterone are low and declining)
  • Surgical laproscopy
Normal Term Pregnancy
  • Not applicable
  • Elevated (>25 mIU/mL)
  • Progressive elevation and doubling of levels every 2 days especially during first 8 weeks
  • Not applicable
  • Absent
  • Not applicable
  • Negative
  • Negative
  • Progressive elevation and doubling of levels every 2 days especially during first 8 weeks
  • Negative
  • Negative
  • Negative
  • Negative
  • Expectant delivery
  • C-section (elective or in cases of breach presentation)

References

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  2. Cavaliere A, Ermito S, Dinatale A, Pedata R (January 2009). "Management of molar pregnancy". J Prenat Med. 3 (1): 15–7. PMC 3279094. PMID 22439034.
  3. Sun SY, Melamed A, Joseph NT, Gockley AA, Goldstein DP, Bernstein MR, Horowitz NS, Berkowitz RS (February 2016). "Clinical Presentation of Complete Hydatidiform Mole and Partial Hydatidiform Mole at a Regional Trophoblastic Disease Center in the United States Over the Past 2 Decades". Int. J. Gynecol. Cancer. 26 (2): 367–70. doi:10.1097/IGC.0000000000000608.
  4. Watson EJ, Hernandez E, Miyazawa K (September 1987). "Partial hydatidiform moles: a review". 42 (9): 540–4.
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  7. Smith HO, Kohorn E, Cole LA (December 2005). "Choriocarcinoma and gestational trophoblastic disease". Obstet. Gynecol. Clin. North Am. 32 (4): 661–84. doi:10.1016/j.ogc.2005.08.001. PMID 16310678.
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  10. Horowitz NS, Goldstein DP, Berkowitz RS (January 2017). "Placental site trophoblastic tumors and epithelioid trophoblastic tumors: Biology, natural history, and treatment modalities". Gynecol. Oncol. 144 (1): 208–214. doi:10.1016/j.ygyno.2016.10.024. PMID 27789086.
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  14. Farahmand SM, Marchetti DL, Asirwatham JE, Dewey MR (May 1991). "Ovarian endodermal sinus tumor associated with pregnancy: review of the literature". Gynecol. Oncol. 41 (2): 156–60. PMID 2050306.
  15. Hopkins MP, Duchon MA (November 1986). "Adnexal surgery in pregnancy". J Reprod Med. 31 (11): 1035–7. PMID 3806533.
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  17. Dgani R, Shoham Z, Atar E, Zosmer A, Lancet M (June 1989). "Ovarian carcinoma during pregnancy: a study of 23 cases in Israel between the years 1960 and 1984". Gynecol. Oncol. 33 (3): 326–31. PMID 2722058.
  18. Lengyel E (September 2010). "Ovarian cancer development and metastasis". Am. J. Pathol. 177 (3): 1053–64. doi:10.2353/ajpath.2010.100105. PMC 2928939. PMID 20651229.
  19. Goel A, Rao NM, Santhi V, Byna SS, Grandhi B, Conjeevaram J (2018). "Immunohistochemical Characterization of Normal Ovary and Common Epithelial Ovarian Neoplasm with a Monoclonal Antibody to Cytokeratin and Vimentin". Iran J Pathol. 13 (1): 23–29. PMC 5929385. PMID 29731792.
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  21. Zhou P, Xiong T, Chen J, Li F, Qi T, Yuan J (February 2019). "Clinical significance of melanoma cell adhesion molecule CD146 and VEGFA expression in epithelial ovarian cancer". Oncol Lett. 17 (2): 2418–2424. doi:10.3892/ol.2018.9840. PMC 6341705. PMID 30675307.
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  23. Barnhart K, Sammel MD, Chung K, Zhou L, Hummel AC, Guo W (November 2004). "Decline of serum human chorionic gonadotropin and spontaneous complete abortion: defining the normal curve". Obstet Gynecol. 104 (5 Pt 1): 975–81. doi:10.1097/01.AOG.0000142712.80407.fd. PMID 15516387.
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  26. Murphy AA, Nager CW, Wujek JJ, Kettel LM, Torp VA, Chin HG (June 1992). "Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial". Fertil. Steril. 57 (6): 1180–5. PMID 1534771.