Case 5 -

Early Complete Hydatidiform Mole Michael Wells University of Sheffield Sheffield, United Kingdom

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Case 5 - Figure 1 Case 5 - Figure 2 Case 5 - Figure 3 Case 5 - Figure 4 Case 5 - Figure 5 Case 5 - Figures 1-5 - Early diploid complete hydatidiform mole. Photomicrographs show abnormally shaped chorionic villi (including branching and polypoid forms), the presence of stromal mucin, and stromal nuclear (apoptotic) debris. Hydatidiform mole may occur in three forms: androgenetic diploid complete mole triploid partial mole invasive mole The chorionic villi in hydatidiform mole show the following features: hydropic change cistern formation excessive trophoblast, abnormal distribution of trophoblast trophoblastic inclusions. In complete hydatidiform mole: all chorionic villi are affected there may be pleomorphism of trophoblast including non-villous trophoblast there is an absence of villous stromal fibrosis In partial mole: fetal parts may be present hydropic change of villi is focal there is usually an irregular or angulated profile to the chorionic villi the apparent excess of trophoblast may be subtle With the increased use of ultrasound complete hydatidiform mole is diagnosed at an increasingly early stage of gestation (the average is now 9.4 weeks compared with 17 weeks in the 1960s). Thus the classical features of complete hydatidiform mole may be lacking. Features of "early" complete hydatidiform mole include: abnormally shaped villi, which may be branching or polypoid stromal mucin presence of stromal vessels STROMAL NUCLEAR DEBRIS The pathological diagnosis of hydatidiform mole is usually made on formalin fixed, paraffin embedded material and molecular analysis is not carried out as a routine investigation. Whilst in most cases the histological distinction between hydropic miscarriage and between partial and complete mole can be made on histological grounds alone, there are equivocal cases for which confirmatory procedures are indicated. Ploidy analysis, usually by flow cytometry, to distinguish between a diploid complete and a triploid partial mole, has been available in some centres for more than 15 years but has the disadvantage of being a blind event without precise histopathological control of the cells being analysed. A new semi-automated digital image analysis system has been applied to molar disease. Microdissected 50 micron sections are digested with enzyme and filtered through a 50 micron mesh to give suspensions of nuclei which are then prepared as cytospin monolayers. The slides are fixed overnight in 4% formalin, Feulgen stained and analyzed by a computer system comprising of two programs: ploidy cell capture histogram draftsman. P57kip2 is: a cyclin-dependent kinase the product of a paternally imprinted, maternally expressed gene expressed by the villous cytotrophoblast of normal pregnancy expressed by villous cytotrophoblast of partial mole not expressed by the villous cytotrophoblast of androgenetic complete mole The application of ploidy analysis combined with p57kip2 has proven effective in facilitating the diagnosis of equivocal cases. For example, a putative partial hydatidiform mole which is diploid and p57kip2 positive is likely to be a non-molar hydropic miscarriage, whilst a putative partial mole which is diploid and p57kip2 negative is actually an early complete mole. The complementary use of these two techniques also provides good quality control of histopathological interpretation and now forms part of the routine diagnostic workup of our cases. References General: Paradinas FJ, Browne P, Fisher RA et al. A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions. Histopathology 1996; 28: 101-109. Paradinas FJ, Elston CW. Gestational trophoblastic diseases. In: Haines & Taylor Obstetrical and Gynaecological Pathology, Edited by H Fox and M Wells, Fifth Edition, Churchill Livingstone, 2003: 1359-1430. P57kip2 Chilosi M, Piazzola E, Lestani M et al. Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease. Lab Invest 1998; 78: 269-276. Genest DR, Dorfman DM, Castrillon DH. Ploidy and imprinting in hydatidiform moles. Complementary use of flow cytometry and immunohistochemistry of the imprinted gene product p57kip2 to assist molar classification. J Reprod Med 2002; 47: 342-346. Jun S-Y, Ro JY, Kim K-R. p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles. Histopathology 2003; 43: 17-25 Digital image analysis and p57kip2 immunohistochemistry Crisp H, Burton JL, Smith O, Stewart R, Wells M. Refining the diagnosis of hydatidiform mole: image ploidy analysis and p57KIP2 immunohistochemistry. Histopathology 2003; 43:363-373