Gestational trophoblastic disease: Pathology
- Rebecca N Baergen, MD
Rebecca N Baergen, MD
- Professor of Clinical Pathology and Laboratory Medicine
- Weill Medical College of Cornell University
Gestational trophoblastic disease comprises a heterogeneous group of related lesions arising from abnormal proliferation of trophoblast of the placenta. The pathogenesis of gestational trophoblastic disease is unique, because the maternal lesions arise from fetal, not maternal, tissue.
The histopathology of gestational trophoblastic disease is discussed here. The epidemiology, clinical manifestations, diagnosis, and treatment of hydatidiform moles and malignant gestational trophoblastic disease are reviewed separately. (See "Hydatidiform mole: Epidemiology, clinical features, and diagnosis" and "Hydatidiform mole: Management" and "Initial management of low-risk gestational trophoblastic neoplasia".)
●Gestational trophoblastic disease (GTD) – Lesions characterized by abnormal proliferation of trophoblast of the placenta. This category is comprised of benign, nonneoplastic lesions including placental site nodule, exaggerated placental site, and hydatidiform mole.
●Gestational trophoblastic neoplasia (GTN) – Gestational neoplasms include: choriocarcinoma, placental site trophoblastic tumor, epithelioid trophoblastic tumor, and invasive mole. In the absence of tissue for a definitive histopathologic diagnosis, disease diagnosed as a result of persistent elevation of human chorionic gonadotropim (hCG) after evacuation of a molar pregnancy is termed GTN.
Most, but not all, GTD produces the beta subunit of human chorionic gonadotropin (hCG). Chromosomal abnormalities are characteristic of some GTD subtypes; assessment of DNA content enhances the diagnostic accuracy of histological diagnosis (see 'Genetics' below) [1,2].
- van de Kaa CA, Schijf CP, de Wilde PC, et al. The role of deoxyribonucleic acid image cytometric and interphase cytogenetic analyses in the differential diagnosis, prognosis, and clinical follow-up of hydatidiform moles. A report from the Central Molar Registration in The Netherlands. Am J Obstet Gynecol 1997; 177:1219.
- Cheung AN, Khoo US, Lai CY, et al. Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole: genotyping and chromosome in situ hybridization analysis. Cancer 2004; 100:1411.
- Shih IeM. Gestational trophoblastic neoplasia--pathogenesis and potential therapeutic targets. Lancet Oncol 2007; 8:642.
- El-Helw LM, Hancock BW. Treatment of metastatic gestational trophoblastic neoplasia. Lancet Oncol 2007; 8:715.
- Davis JR, Surwit EA, Garay JP, Fortier KJ. Sex assignment in gestational trophoblastic neoplasia. Am J Obstet Gynecol 1984; 148:722.
- Chiu PM, Liu VW, Ngan HY, et al. Detection of mitochondrial DNA mutations in gestational trophoblastic disease. Hum Mutat 2003; 22:177.
- Li HW, Tsao SW, Cheung AN. Current understandings of the molecular genetics of gestational trophoblastic diseases. Placenta 2002; 23:20.
- Fulop V, Mok SC, Genest DR, et al. c-myc, c-erbB-2, c-fms and bcl-2 oncoproteins. Expression in normal placenta, partial and complete mole, and choriocarcinoma. J Reprod Med 1998; 43:101.
- Tuncer ZS, Vegh GL, Fulop V, et al. Expression of epidermal growth factor receptor-related family products in gestational trophoblastic diseases and normal placenta and its relationship with development of postmolar tumor. Gynecol Oncol 2000; 77:389.
- Fulop V, Mok SC, Genest DR, et al. p53, p21, Rb and mdm2 oncoproteins. Expression in normal placenta, partial and complete mole, and choriocarcinoma. J Reprod Med 1998; 43:119.
- Shih IeM, Kurman RJ. Molecular basis of gestational trophoblastic diseases. Curr Mol Med 2002; 2:1.
- Shih IM, Seidman JD, Kurman RJ. Placental site nodule and characterization of distinctive types of intermediate trophoblast. Hum Pathol 1999; 30:687.
- Shih IM, Kurman RJ. The pathology of intermediate trophoblastic tumors and tumor-like lesions. Int J Gynecol Pathol 2001; 20:31.
- Seckl MJ, Fisher RA, Salerno G, et al. Choriocarcinoma and partial hydatidiform moles. Lancet 2000; 356:36.
- Niemann I, Petersen LK, Hansen ES, Sunde L. Predictors of low risk of persistent trophoblastic disease in molar pregnancies. Obstet Gynecol 2006; 107:1006.
- Jacobs PA, Wilson CM, Sprenkle JA, et al. Mechanism of origin of complete hydatidiform moles. Nature 1980; 286:714.
- Fisher RA, Hodges MD. Genomic imprinting in gestational trophoblastic disease--a review. Placenta 2003; 24 Suppl A:S111.
- Fisher RA, Hodges MD, Rees HC, et al. The maternally transcribed gene p57(KIP2) (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles. Hum Mol Genet 2002; 11:3267.
- Fisher RA, Hodges MD, Newlands ES. Familial recurrent hydatidiform mole: a review. J Reprod Med 2004; 49:595.
- Deveault C, Qian JH, Chebaro W, et al. NLRP7 mutations in women with diploid androgenetic and triploid moles: a proposed mechanism for mole formation. Hum Mol Genet 2009; 18:888.
- Parry DA, Logan CV, Hayward BE, et al. Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte. Am J Hum Genet 2011; 89:451.
- Fisher RA, Newlands ES. Gestational trophoblastic disease. Molecular and genetic studies. J Reprod Med 1998; 43:87.
- Lage JM, Mark SD, Roberts DJ, et al. A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy. Obstet Gynecol 1992; 79:403.
- Genest DR, Ruiz RE, Weremowicz S, et al. Do nontriploid partial hydatidiform moles exist? A histologic and flow cytometric reevaluation of nontriploid specimens. J Reprod Med 2002; 47:363.
- Baergen RN, Kelly T, McGinniss MJ, et al. Complete hydatidiform mole with a coexistent embryo. Hum Pathol 1996; 27:731.
- Castrillon DH, Sun D, Weremowicz S, et al. Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of the paternally imprinted gene product p57KIP2. Am J Surg Pathol 2001; 25:1225.
- Keep D, Zaragoza MV, Hassold T, Redline RW. Very early complete hydatidiform mole. Hum Pathol 1996; 27:708.
- Lipata F, Parkash V, Talmor M, et al. Precise DNA genotyping diagnosis of hydatidiform mole. Obstet Gynecol 2010; 115:784.
- Lee Y, Kim KR, McKeon F, et al. A unifying concept of trophoblastic differentiation and malignancy defined by biomarker expression. Hum Pathol 2007; 38:1003.
- Mao TL, Kurman RJ, Huang CC, et al. Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis. Am J Surg Pathol 2007; 31:1726.
- Benirschke K, Kaufmann P, Baergen RN. Pathology of the Human Placenta, Springer, New York 2006. p.191.
- Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl J Med 1996; 335:1740.
- Shih IM, Kurman RJ. 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 1998; 29:27.
- Lage JM. The placenta. In: Pathology in obstetrics and gynecology, 4th, Gompel C, Silverberg SG (Eds), Lippincott, Philadelphia 1994. p.448.
- Fisher RA, Newlands ES, Jeffreys AJ, et al. Gestational and nongestational trophoblastic tumors distinguished by DNA analysis. Cancer 1992; 69:839.
- Scully RE, Young RH. Trophoblastic pseudotumor: a reappraisal. Am J Surg Pathol 1981; 5:75.
- Hoekstra AV, Keh P, Lurain JR. Placental site trophoblastic tumor: a review of 7 cases and their implications for prognosis and treatment. J Reprod Med 2004; 49:447.
- Baergen RN, Rutgers JL, Young RH, et al. Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 2006; 100:511.
- Vardar MA, Altintas A. Placental-site trophoblastic tumor. Principles of diagnosis, clinical behaviour and treatment. Eur J Gynaecol Oncol 1995; 16:290.
- Kashimura M, Kashimura Y, Oikawa K, et al. Placental site trophoblastic tumor: immunohistochemical and nuclear DNA study. Gynecol Oncol 1990; 38:262.
- Shih IM, Kurman RJ. Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 1998; 22:1393.
- Palmer JE, Macdonald M, Wells M, et al. Epithelioid trophoblastic tumor: a review of the literature. J Reprod Med 2008; 53:465.
- Allison KH, Love JE, Garcia RL. Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast. Arch Pathol Lab Med 2006; 130:1875.
- Shih IM, Kurman RJ. p63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations. Am J Surg Pathol 2004; 28:1177.
- Types of GTD
- - Benign nonneoplastic trophoblastic lesions
- - Hydatidiform mole
- - Gestational trophoblastic neoplasia (GTN)
- BENIGN NONNEOPLASTIC TROPHOBLASTIC LESIONS
- Exaggerated placental site
- Placental site nodule
- HYDATIFORM MOLE
- Genetics of molar pregnancy
- Complete mole genetics
- Partial mole genetics
- - Complete mole
- - Early complete mole
- - Partial mole
- - Invasive mole
- GESTATIONAL TROPHOBLASTIC NEOPLASIA
- GTN following molar pregnancy
- Types of GTN
- - Choriocarcinoma
- - Placental site trophoblastic tumors
- - Epithelioid trophoblastic tumor