51
In conclusion, GTD continues to be an important spectrum of diseases affecting women of mainly the reproductive age, especially in developing countries like Nigeria, with a significant propensity to develop from benign to malignant disease, as reflected in the number of instances of malignant disease (choriocarcinoma was the second commonest form of GTD in this study).
Although GTD is reported to have become less of a health problem in recent years in advanced countries, the same cannot be said of developing areas like our environment, where the prevalence appears to have been rising in recent years, though the overall pattern is largely unchanged for now. The rising prevalence may be partly attributable to the relatively increased availability and utilization of histopathological services in recent years in this environment. A point to note however is that cases of GTD arising in ectopic primary sites seem to be appearing with increasing frequency.
52
REFERENCES
1. Hui P, Martel M, Parkash V. Gestational trophoblastic diseases: recent advances in histopathologic diagnosis and related genetic aspects. Adv Anat Pathol. 2005; 12:116-125.
2. Horn L, Einenkel J, Hoehn K. Classification and morphology of gestational trophoblastic disease. Curr Obstet Gynecol Rep. 2014; 3: 44–54.
3. Shih IM, Mazur MT, Kurman RJ. Gestational trophoblastic tumours and related tumour-like conditions. In: Kurman RJ (ed). Blaustein’s pathology of the female genital tract. 6th ed. New York. Springer-Velag.2011; pp 1075-1135.
4. Shih IM, Kurman RJ. Epithelioid trophoblastic tumour: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumour simulating carcinoma. Am J Surg Pathol. 1998; 22:1393-1403.
5. Shih IM, Seidman JD, Kurman RJ. Placental site nodule and characteristics of a distinctive type of intermediate trophoblast. Hum Pathol. 1999; 30:687-694.
6. Agboola A, Abudu O. Epidemiology of trophoblastic disease in Africa – Lagos. Advances in Experimental Medicine and Biology 1984; 176:187-195.
7. Mbamara SU, Obiechina N, Eleje GU, Akabuike CJ, Umeononihu OS. Gestational trophoblastic disease in a tertiary hospital in Nnewi, southeast Nigeria. Niger Med J.
2009;50:87-89.
8. Eniola OA, Mabayoje P, Ogunniyi SO. Hydatidiform mole in Ile-Ife, Nigeria: a 10-year review. J Obstet Gynaecol. 2001; 21:405-407.
9. Ocheke AN, Musa J, Uamai AO. Hydatidiform mole in Jos, Nigeria. Niger Med J. 2011;
52:223-226.
53
10. Mayun AA. Hydatidiform mole in Gombe: a five year histopathological review. Niger J Clin Pract. 2008; 11:134-138.
11. Aligbe JU, Ekanem VJ, Akhiwu WO, Banjo AA. Gestational trophoblastic disease (GTD):
a ten year review of clinicopathologic features of cases seen at the University of Benin Teaching Hospital, Benin City. Ann Biomed Sci. 2002; 1:94-99.
12. Shih IM, Marzur MT, Kurman RJ. Gestational trophoblastic tumors and related tumor-like lesions. In: Kurman RJ, Ellenson LH, Ronnett BM (eds). Blaustein’s pathology of the female genital tract. 6th ed. New York. Springer. 2011;pp1076-1126.
13. Rosai J. Pregnancy, trophoblastic disease and placenta. In: Rosai J (ed). Rosai and Ackerman’s surgical pathology. Mosby Elsevier: 10th edition, New York. 2011;pp1636-1645.
14. McCluggage WG: Recent advances in immunohistochemistry in gynaecological pathology. Histopathology. 2002; 40:309-326.
15. Singer G, Kurman RJ, McMaster MT, Shih IM. HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis. Am J Surg Pathol. 2002; 26:914-920.
16. Li HW, Cheung AN, Tsao SW, Cheung AL. Expression of E-cadherin and beta-catenin in trophoblastic tissue in normal and pathological pregnancies. Int J Gynecol Pathol. 2002; 22:63-70.
17. Hando T, Ohno M, Kurose T. Recent aspects of gestational trophoblastic disease in Japan.
Int J Gynaecol Obstet. 1998;60:71–76.
18. Altieri A, Franceschi S, Ferlay J, Smith J, La Vecchia C. Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol. 2003; 4:670–678.
54
19. Al Alaf SK, Omer DI. Prevalence and clinical observations of gestational trophoblastic diseases in a maternity teaching hospital in Erbil City. Trans Biol Biomed.2010; 3:190-199.
20. Nizam K, Haider G, Memon N, Haider A. Gestational trophoblastic disease: experience at Nawabshah hospital. J Ayub Med Coll Abbottabad.2009; 21:94-97.
21. Chong CY, Koh CG. Hydatidiform mole in Kendang Kerbau Hospital – a 5-year review.
Singapore Med J. 1999; 40:265-270.
22. Cagayan MS. Changing trends in the management of gestational trophoblastic diseases in the Philippines. J Reprod Med. 2010; 55:267-272.
23. Cheah P, Looi L, Sivanesaratnam V. Hydatidiform molar pregnancy in Malaysian women:
a histopathological study from the University Hospital, Kuala Lumpur. Malays J Pathol.
1993; 15:59-63.
24. Chechia A, Koubaa A, Makhlouf T, Anis B,Terras K et al. Molar pregnancy.
Retrospective study of 60 cases in Tunisia. Tunis Med. 2001; 79:441– 446.
25. Boufettal H, Coullin P, Mahdaoui S, Noun M, Hermas S et al. Complete hydatidiform mole in Morocco: epidemiological and clinical study. J Gynecol Obstet Biol Reprod.
2011; 40:419-429.
26. Mayun AA, Rafindadi AH, Shehu MS. Pathomorphology of molar gestation in Zaria.
Niger Med J. 2010; 51:1-4.
27. Audu BM, Takai IU, Chama CM, Bukar M, Kyari O. Hydatidiform mole as seen in a university teaching hospital: a ten year review. J ObstetGynaecol. 2009; 29:322-325.
28. Ekpo MD. Hydatidiform mole in Nigeria. J ObstetGynaecol. 1990; 10:363-366.
55
29. Egwuatu VE, Ozumba BC. Observations on molar pregnancy in Enugu, Nigeria. Int J Gynaecol Obstet.1989; 29:219-225.
30. Osamor JO, Oluwasola AO, Adewole IF. A clinico-pathological study of complete and partial hydatidiform moles in a Nigerian population. J Obstet Gynaecol. 2002; 22:423-425.
31. Palmer JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med.1994;39:155–162.
32. Reid A, Heyworth J, de Klerk N, Musk AW. Asbestos exposure and gestational trophoblastic disease: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2009; 18:2895–
2898.
33. Kaye DK. Gestational trophoblastic disease following complete hydatidiform mole in Mulago Hospital, Kampala, Uganda. Afr Health Sci. 2002; 2:47–51.
34. Talati NJ. The pattern of benign gestational trophoblastic disease in Karachi. J Pak Med Assoc. 1998; 48:296-300.
35. Razieh M, Parvin A, Mitra T. The gestational trophoblastic diseases: a ten year retrospective study. IJFS. 2010; 4:1-4.
36. Graham IH, Fajardo AM, Richards RL. Epidemiological study of complete and partial hydatidiform mole in Abu Dhabi: influence of age and ethnic group. J ClinPathol. 1990;
43:661–664.
37. Ben Temime R, Chechia A, Hannachi W, Attia L, Makhlouf T, Koubaa A. Clinical analysis and management of gestational trophoblastic diseases: a 90 cases study. Int J Biomed Sci. 2009; 5:321-325.
56
38. Jacobs PA, Hunt PA, Matsuura JS, Wilson CC, Szulman AE. Complete and partial hydatidiform mole in Hawaii: cytogenetics, morphology and epidemiology. BJOG. 2005;
89:258-266.
39. Khashoggi TY. Prevalence of gestational trophoblastic disease: a single institution experience. Saudi Med J. 2003; 24:1329-1333.
40. Lorigan PC, Sharma S, Bright N, Coleman RE, Hancock BW. Characteristics of women with recurrent molar pregnancies. GynecolOncol.2000; 78:288-292.
41. Palmer JR. Oral contraceptive use and gestational choriocarcinoma. Cancer Detect Prev. 1991; 15:45-48.
42. Palmer JR, Driscoll SG, Rosenberg L, Berkowitz RS, Lurain JR et al. Oral contraceptive use and risk of gestational trophoblastic tumors. J Natl Cancer Inst. 1999; 91:635-640.
43. Bashabsheh MA. Maternal age-related rates of gestational trophoblastic disease in a sample from Department of Obstetrics and Gynaecology at Damascus University. Eur J Sci Res. 2011; 55:521-526.
44. Garner EI, Goldstein DP, Feltmate CM, Berkowitz RS. Gestational trophoblastic disease.
Clin Obstet Gynecol. 2007; 50:112–122.
45. Lai CY, Chan KY, Khoo US, Ngan HY, Xue WC et al. Analysis of gestational trophoblastic disease by genotyping and chromosome in situ hybridization. Mod Pathol.
2004; 17:40-48.
46. Howat AJ, Beck S, Fox H, Harris SC, Hill AS et al. Can histopathologists reliably diagnose molar pregnancy? J ClinPathol. 1993; 46:599–602.
57
47. Jeffers MD, O’Dwyer P, Curran B, Leader M, Gillan JE. Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis. Int J Gynecol Pathol. 1993; 12:315-323.
48. Bell KA, Van Deerlin V, Addya K, Clevenger CV, Van Deerlin PG, Leonard DG.
Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole. Mol Diagn.1999; 4:11-19.
49. Vang R, Gupta M, Wu LS, Yemelyanova AV, Kurman RJ, et al. Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57 immunohistochemistry and molecular genotyping) improve morphologic diagnosis. Am J Surg Pathol.2012;
36:443-453.
50. Ronnett BM, DeScipio C, Murphy KM. Hydatidiform moles: ancillary techniques to refine diagnosis. Int J GynecolPathol.2011; 30:101-116.
51. Jelincic D, Hudelist G, Singer CF, Bauer M, Horn LC, et al. Clinicopathologic profile of gestational trophoblastic disease. Wien Klin Wochenschr. 2003; 115:29-35.
52. Shih IM, Kurman RJ. Molecular basis of gestational trophoblastic diseases. Curr Mol Med. 2002;2:1–12.
53. Li HW, Tsao SW, Cheung AN. Current understandings of the molecular genetics of gestational trophoblastic diseases. Placenta. 2002; 23:20–31.
54. Bifulco C, Johnson C, Hao L, Kermalli H, Bell S, Hui P. Genotypic analysis of hydatidiform mole: an accurate and practical method of diagnosis. Am J Surg Pathol.
2008; 32:445–451.
55. McConnell TG, Murphy KM, Hafez M, Vang R, Ronnett B. Diagnosis and sub classification of hydatidiform moles using p57immunohistochemistry and molecular
58
genotyping: validation and prospective analysis in routine and consultation practice settings with development of an algorithmic approach. Am J Surg Pathol. 2009; 33:805–
817.
56. Keep D, Zaragoza MV, Hassold T, Redline RW. Very early complete hydatidiform mole.
Hum Pathol.1996; 27:708–713.
57. Kim MJ, Kim KR, Ro JY, Lage JM, Lee HI. Diagnostic and pathogenetic significance of increased stromal apoptosis and incomplete vasculogenesis in complete hydatidiform moles in very early pregnancy periods. Am J Surg Pathol.. 2006;30:362–369.
58. Genest DR. Partial hydatidiform mole: clinicopathological features, differential diagnosis, ploidy and molecular studies, and gold standards for diagnosis. Int J Gynecol Pathol.
2001; 20:315–322.
59. Chew SH, Perlman EJ, Williams R, Kurman RJ, Ronnett BM. Morphology and DNA content analysis in the evaluation of first trimester placentas for partial hydatidiform mole (PHM). Hum Pathol. 2000; 31:914–924.
60. McConnell TG, Norris-Kirby A, Hagenkord JM, Ronnett BM, Murphy KM. Complete hydatidiform mole with retained maternal chromosomes 6 and 11. Am J Surg Pathol.
2009; 33:1409–1415.
61. Wells M. The pathology of gestational trophoblastic disease: Recent advances. Pathology.
2007; 39:88–96.
62. Lipata F, Parkash V, TalmorM, Bell S, Chen S, et al. Precise DNA genotyping diagnosis of hydatidiform mole. Obstet Gynecol. 2010; 115:784–794.
63. Kurman RJ. Pathology of trophoblast. Monogr Pathol. 1991; 33:195-227.
59
64. Berkowitz RS, Goldstein DP, Bernstein MR. Choriocarcinoma following term gestation. Gynecol Oncol. 1984; 17:52-57.
65. Barghorn A, Bannwart F, Stallmach T. Incidental choriocarcinoma confined to a near-term placenta. Virchows Arch. 1998; 433:89-91.
66. Fukunaga M, Nomura K, Ushigome S. Choriocarcinoma in situ of a first trimester: report of two cases indicating an origin of trophoblast of a stem villus. Virchows Arch. 1996; 429:185-188.
67. Mazur MT, Lurain JR, Brewer JI. Fatal gestational choriocarcinoma. Clinicopathologic study of patients treated at a trophoblastic disease center. Cancer. 1982; 50:1833-1846.
68. Heaton GE, Matthews TH, Christopherson WM. Malignant trophoblastic tumours with massive hemorrhage presenting as liver primary. A report of two cases. Am J Surg Pathol. 1986; 10:342-347.
69. Tsukamoto N, Matsumura M, Matsukuma K, Kamura T, Baba K. Choriocarcinoma in mother and fetus. Gynecol Oncol. 1986; 24:113-119.
70. Ober WB, Edgcomb JH, Price Jr EB. The pathology of choriocarcinoma. Ann N Y Acad Sci. 1971; 172:299-321.
71. Silva EG, Tornos C, Lage J, Ordonez NG, Morris M, Kavanagh J. Multiple nodules of intermediate trophoblast following hydatidiform moles. Int J Gynecol
Pathol. 1993; 12:324-332.
72. Hui P, Parkash V, Perkins AS, Carcangiu ML. Pathogenesis of placental site trophoblastic tumour may require the presence of a paternally derived X chromosome. Lab Invest. 2000; 80:965-972.
60
73. Berger G, Verbaere J, Feroldi J. Placental site trophoblastic tumour of the uterus. An ultrastructural and immunohistochemical study. Ultrastruct Pathol. 1984; 6:319-329.
74. Bamberger AM, Sudhal S, Wagener C, Loning T. Expression pattern of the adhesion molecule CEACAM1 (C-CAM, CD66a, BGP) in gestational trophoblastic lesions. Int J Gynecol Pathol. 2001; 20:160-165.
75. Kotylo PK, Michael H, Davis TE, Sutton GP, Mark PR, Roth LM. Flow cytometric DNA analysis of placental-site trophoblastic tumors. Int J Gynecol Pathol. 1992;11:245-252.
76. Shih IM, Kurman RJ. Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumour, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and MEL-CAM antibodies. Hum Pathol. 1998; 29:27-33.
77. Mazur MT. Metastatic gestational choriocarcinoma. Unusual pathologic variant following therapy. Cancer. 1989; 63:1370-1377.
78. Fadare O, Parkash V, Carcangiu ML, Hui P. Epithelioid trophoblastic tumour:
clinicopathological features with an emphasis on uterine cervical involvement. Mod Pathol. 2006; 19:75-82.
79. Kuo KT, Chen MJ, Lin MC. Epithelioid trophoblastic tumuor of the broad ligament: a case report and review of the literature. Am J Surg Pathol. 2004; 28:405-409.
80. Lewin SN, Aghajanian C, Moreira AL, Soslow RA. Extrauterine epithelioid trophoblastic tumours presenting as primary lung carcinomas: morphologic and immunohistochemical features to resolve a diagnostic dilemma. Am J Surg Pathol. 2009; 33:1809-1814.
61
81. Hamazaki S, Nakamoto S, Okino T, Tsukayama C, Mori M, Taguchi K et al. Epithelioid trophoblastic tumor: morphological and immunohistochemical study of three lung lesions. Hum Pathol. 1999; 30:1321-1327.
82. Shih IM, Kurman RJ. Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol. 1998; 22:1393-1403.
83. Huettner PC, Gersell DJ. Placental site nodules. A clinicopathologic study of 38 cases. Int J Gynecol Pathol. 1994;13:191-198.
84. Moodley M, Tunkyi K, Moodley J. Gestational trophoblastic syndrome: an audit of 112 patients. A South African experience. Int J Gynaecol Cancer.2003; 13:234-239.
85. Horn L, Bilek K. Clinicopathologic analysis of gestational trophoblastic disease – report of 158 cases. Gen Diagn Pathol. 1997; 143:173-178.
86. Lurain JR. Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. AJOG. 2011; 204: 11-18.
62
APPENDIX I
WORLD HEALTH ORGANISATION (WHO) 2008 CLASSIFICATION OF GESTATIONAL TROPHOBLASTIC DISEASE2
Complete hydatidiform mole (CHM) Partial hydatidiform mole (PHM) Invasive hydatidiform mole (IHM) Gestational choriocarcinoma (CC)
Placental site trophoblastic nodule (PSN) Exaggerated placental site (EPS)
Placental-site trophoblastic tumour (PSTT) Epithelioid trophoblastic tumour (ETT) Mixed or unclassified trophoblastic lesions