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
Differential Diagnosis	Presenting Complaints	Potential for Neoplastic Conversion	Beta Human Chorionic Gonadotropin (Beta-hCG) Baseline Levels	History of Pregnancy	Theca Leutin Cysts	Metastatic Route	Karyotype	Cytokeratin 18	HLA-G	Human Chorionic Gonadotropin (hCG)	Transformation-Related Protein 63 (P63)	Human Placental Lactogen (hPL)	Melanoma Cell Adhesion Molecule (Mel-CAM)	Ki67	Management
Complete Hydatidiform Mole^[1]^[2]^[3]	Vaginal bleeding Inappropriately large for date uterine size Hyperemesis Vaginal passage of grape-like vescicles	High rate of progression (15-20%)	Extremely high levels >100000 mIU/ml in half of the patients	Not related	Present	Benign	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]	Vaginal bleeding	< 5 % progression rate	Highly elevated >100000 mIU/ml in one in ten patients	Not related	Absent	Benign	69,XXY or XYY	Negative	Negative	Highly elevated	Absent	Absent	Absent	Absent	Dilation and curettage (suction)
Invasive Molar Pregnancy	Vaginal bleeding Elevated beta-hCG	Neoplastic	High	Consequence of molar pregnancy	May be present	Hematogenous	69,XXY or XYY	Positive	Positive	Highly elevated	Absent	Absent	Absent	Absent	Chemotherapy (Methotrexate)
Choriocarcinoma^[7]^[8]^[9]	Vaginal bleeding Weight loss	Neoplastic	High	Approximately half of the cases occur as a consequence of molar pregnancy Quarter of the cases follow abortion or tubal pregnancy Rest follow term or pre-term pregnancy	Present	Hematogenous		Positive	Positive	Highly elevated			Positive
Placental-site Trophoblastic tumor (PSTT) and Epitheloid Trophoblastic Tumor (ETT)^[10]^[11]^[12]^[13]	Vaginal bleeding	Neoplastic	Moderatley elevated <1000 mIU/ml in majority of patients	About 60% follow term pregnancy 40 % follow molar pregnancy or abortion	Absent	Lymphatic	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]	Vaginal bleeding or discharge Weight loss Urinary frequency/urgency Change in bowel habits Loss of appetite Pelvic pressure/pain Abdominal pain	Neoplastic	Elevated (Dysgerminoma and Embryonal carcinoma)	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	46,XX	Negative (Epithelial tumors may be positive for cytokeratin AE1/AE3)	Positive	Elevated in dysgerminomas and embryonal carcinoma)	Positive (especially in epithelial cancers)	Positive	Positive	Positive	Surgical debulking Intravenous/intraperitoneal chemotherapy
Spontaneous Abortion^[23]^[24]	Vaginal bleeding Lower abdominal pain Lower back pain Vaginal passage of fetal tissue Reduced uterine size and regression of signs and symptoms of pregnancy Firm cervix	Not applicable	Decline in levels within 24 hours	Aneuploid pregnancy History of recurrent pregnancy loss	Absent	Not applicable	47,XX, +21 or 47, XY, +21 (Down's syndrome) 47,XX,+18 or 47, XY, +18 (Edward's syndrome) 47,XX, +13 or 47, XY, +13 (Patau syndrome)	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]	Abdominal/pelvic pain Vaginal bleeding Amenorrhea Nausea Syncope	Not applicable	Failure of hCG doubling (especially during the first 8 weeks)	Previous ectopic pregnancy Intrauterine exposure to diethylstillbestrol Current use of intrauterine contraceptive device Advanced maternal age	Absent	Not applicable	46,XX or 46, XY	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	Uterine enlargment Nausea with or without vomiting Breast tenderness Amenorrhea Cervix is firm, long and closed Headache Urinary urgency Fatigue	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	46,XX or 46, XY	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

↑ Candelier JJ (March 2016). "The hydatidiform mole". Cell Adh Migr. 10 (1–2): 226–35. doi:10.1080/19336918.2015.1093275. PMC 4853053. PMID 26421650.
↑ 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.
↑ 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.
↑ Watson EJ, Hernandez E, Miyazawa K (September 1987). "Partial hydatidiform moles: a review". 42 (9): 540–4.
↑ Goldstein DP, Berkowitz RS (March 1994). "Current management of complete and partial molar pregnancy". J Reprod Med. 39 (3): 139–46. PMID 8035368.
↑ Szulman AE, Surti U (May 1982). "The clinicopathologic profile of the partial hydatidiform mole". Obstet Gynecol. 59 (5): 597–602. PMID 7070731.
↑ 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.
↑ Baergen RN (November 1997). "Gestational choriocarcinoma". Gen Diagn Pathol. 143 (2–3): 127–41. PMID 9443570.
↑ Duffy L, Zhang L, Sheath K, Love DR, George AM (December 2015). "The Diagnosis of Choriocarcinoma in Molar Pregnancies: A Revised Approach in Clinical Testing". J Clin Med Res. 7 (12): 961–6. doi:10.14740/jocmr2236w. PMC 4625817. PMID 26566410.
↑ 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.
↑ Kim SJ (December 2003). "Placental site trophoblastic tumour". Best Pract Res Clin Obstet Gynaecol. 17 (6): 969–84. PMID 14614893.
↑ Zhao J, Lv WG, Feng FZ, Wan XR, Liu JH, Yi XF, Qu PP, Xue FX, Wu YM, Zhao X, Ren T, Yang JJ, Xie X, Xiang Y (July 2016). "Placental site trophoblastic tumor: A review of 108 cases and their implications for prognosis and treatment". Gynecol. Oncol. 142 (1): 102–108. doi:10.1016/j.ygyno.2016.05.006. PMID 27168005.
↑ Shih IM, Kurman RJ (January 1998). "Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies". Hum. Pathol. 29 (1): 27–33. PMID 9445130.
↑ 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.
↑ Hopkins MP, Duchon MA (November 1986). "Adnexal surgery in pregnancy". J Reprod Med. 31 (11): 1035–7. PMID 3806533.
↑ Lavery JP, Koontz WL, Layman L, Shaw L, Gumpel U (October 1986). "Sonographic evaluation of the adnexa during early pregnancy". Surg Gynecol Obstet. 163 (4): 319–23. PMID 3532382.
↑ 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.
↑ 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.
↑ 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.
↑ Rebmann V, Regel J, Stolke D, Grosse-Wilde H (October 2003). "Secretion of sHLA-G molecules in malignancies". Semin. Cancer Biol. 13 (5): 371–7. PMID 14708717.
↑ 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.
↑ Mita S, Nakai A, Maeda S, Takeshita T (December 2004). "Prognostic significance of Ki-67 antigen immunostaining (MIB-1 monoclonal antibody) in ovarian cancer". J Nippon Med Sch. 71 (6): 384–91. PMID 15673959.
↑ 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.
↑ Griebel CP, Halvorsen J, Golemon TB, Day AA (October 2005). "Management of spontaneous abortion". Am Fam Physician. 72 (7): 1243–50. PMID 16225027.
↑ Murray H, Baakdah H, Bardell T, Tulandi T (October 2005). "Diagnosis and treatment of ectopic pregnancy". CMAJ. 173 (8): 905–12. doi:10.1503/cmaj.050222. PMC 1247706. PMID 16217116.
↑ 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.

[pmid26421650-1] Candelier JJ (March 2016). "The hydatidiform mole". Cell Adh Migr. 10 (1–2): 226–35. doi:10.1080/19336918.2015.1093275. PMC 4853053. PMID 26421650.

[pmid22439034-2] 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.

[pmid-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.

[pmid2-4] Watson EJ, Hernandez E, Miyazawa K (September 1987). "Partial hydatidiform moles: a review". 42 (9): 540–4.

[pmid8035368-5] Goldstein DP, Berkowitz RS (March 1994). "Current management of complete and partial molar pregnancy". J Reprod Med. 39 (3): 139–46. PMID 8035368.

[pmid7070731-6] Szulman AE, Surti U (May 1982). "The clinicopathologic profile of the partial hydatidiform mole". Obstet Gynecol. 59 (5): 597–602. PMID 7070731.

[pmid16310678-7] 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.

[pmid9443570-8] Baergen RN (November 1997). "Gestational choriocarcinoma". Gen Diagn Pathol. 143 (2–3): 127–41. PMID 9443570.

[pmid26566410-9] Duffy L, Zhang L, Sheath K, Love DR, George AM (December 2015). "The Diagnosis of Choriocarcinoma in Molar Pregnancies: A Revised Approach in Clinical Testing". J Clin Med Res. 7 (12): 961–6. doi:10.14740/jocmr2236w. PMC 4625817. PMID 26566410.

[pmid27789086-10] 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.

[pmid14614893-11] Kim SJ (December 2003). "Placental site trophoblastic tumour". Best Pract Res Clin Obstet Gynaecol. 17 (6): 969–84. PMID 14614893.

[pmid27168005-12] Zhao J, Lv WG, Feng FZ, Wan XR, Liu JH, Yi XF, Qu PP, Xue FX, Wu YM, Zhao X, Ren T, Yang JJ, Xie X, Xiang Y (July 2016). "Placental site trophoblastic tumor: A review of 108 cases and their implications for prognosis and treatment". Gynecol. Oncol. 142 (1): 102–108. doi:10.1016/j.ygyno.2016.05.006. PMID 27168005.

[pmid9445130-13] Shih IM, Kurman RJ (January 1998). "Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies". Hum. Pathol. 29 (1): 27–33. PMID 9445130.

[pmid2050306-14] 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.

[pmid3806533-15] Hopkins MP, Duchon MA (November 1986). "Adnexal surgery in pregnancy". J Reprod Med. 31 (11): 1035–7. PMID 3806533.

[pmid3532382-16] Lavery JP, Koontz WL, Layman L, Shaw L, Gumpel U (October 1986). "Sonographic evaluation of the adnexa during early pregnancy". Surg Gynecol Obstet. 163 (4): 319–23. PMID 3532382.

[pmid2722058-17] 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.

[pmid20651229-18] 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.

[pmid29731792-19] 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.

[pmid14708717-20] Rebmann V, Regel J, Stolke D, Grosse-Wilde H (October 2003). "Secretion of sHLA-G molecules in malignancies". Semin. Cancer Biol. 13 (5): 371–7. PMID 14708717.

[pmid30675307-21] 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.

[pmid15673959-22] Mita S, Nakai A, Maeda S, Takeshita T (December 2004). "Prognostic significance of Ki-67 antigen immunostaining (MIB-1 monoclonal antibody) in ovarian cancer". J Nippon Med Sch. 71 (6): 384–91. PMID 15673959.

[pmid15516387-23] 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.

[pmid16225027-24] Griebel CP, Halvorsen J, Golemon TB, Day AA (October 2005). "Management of spontaneous abortion". Am Fam Physician. 72 (7): 1243–50. PMID 16225027.

[pmid16217116-25] Murray H, Baakdah H, Bardell T, Tulandi T (October 2005). "Diagnosis and treatment of ectopic pregnancy". CMAJ. 173 (8): 905–12. doi:10.1503/cmaj.050222. PMC 1247706. PMID 16217116.

[pmid1534771-26] 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.

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Gestational trophoblastic neoplasia differential diagnosis

Overview

Differentiating Choriocarcinoma From Other Diseases

References

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