Correction to: Practical guidelines of the EOTTD for pathological and genetic diagnosis of hydatidiform moles (Virchows Archiv, (2024), 484, 3, (401-422), 10.1007/s00428-023-03658-8)

Abstract

In this article, the figures and captions have been interchanged; the figure(s) should have appeared as shown below Figs. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11: (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) (Figure presented.) Partial hydatidiform mole (PHM) pathological features. a) to d) PHM (13 weeks of gestational age). a) Triploid fetus. At the autopsy examination, microcephaly, neck swelling, anteverted nostrils, low-setting ears, arachnodactyly, hypoplasia of thymus and adrenal glands, were described. b) Gross features of placental tissue in liquid milieu highlighting the presence of normal villi intermixed with vesicular villi. c) Histologically there were two distinct populations of villi, large hydropic villi, sometimes with cistern formation, and small to normal-sized villi. Trophoblast hyperplasia was focal and mild. d) Villus with prominent vessel proliferation containing nucleated red blood cells. e) and f) PHM (8 weeks of gestation). e) Two apparent populations of villi, some enlarged and edematous. f) Focal irregular and angulated villi associated with trophoblast pseudoinclusions and focal syncytiotrophoblastic proliferation Complete hydatidiform mole (CHM) pathological features. a) to c) CHM (14 weeks of gestational age). a) Diffuse vesicular change of villi, with a “bunch of grapes” appearance at gross examination in a liquid milieu. b) Histologically villi were diffusely enlarged, with hydropic changes and cisterns. c) Trophoblastic atypia and hyperplasia, with trophoblast degenerative changes and necrosis. d) to f) Early CHM (8 weeks of gestational age). d) Villi with bulbous appearance, narrow cleft-like trophoblast invaginations and hypercellular myxoid villous stroma. e) Focal villous trophoblast circumferential proliferation with a lace-like appearance. f) Marked stromal karyorrhexis Algorithmic approach to the diagnosis of hydatidiform moles. Morphological features are the base of diagnostic approach supported by p57 immunohistochemistry, ploidy and genotyping. An alternative approach may be considered starting with universal p57 immunohistochemistry to all possible HMs. This algorithm applies to common CHM and PHM, acknowledging that there are several rare exceptions such as biparental CHM, mosaic/chimera, twin pregnancies, as well as HMs with uncommon p57 expression and chromosomal anomalies p57 immunoexpression patterns. a) Positive (presence of stromal and cytotrophoblast expression). b) Negative (absence of stromal and cytotrophoblast expression). c) Divergent (coexisting negative and positive villi). d) Discordant (absence of stromal expression and presence of cytotrophoblast expression). e) Diagrams showing the relationship between immunostaining p57 patterns and genetic background Conventional karyotype. a) Diploid conceptus showing a normal 46,XX karyotype. b) Triploid conceptus showing a 69,XXX karyotype. These results, interpreted together with morphological features, may support the diagnosis of CHM and PHM, respectively Ploidy analysis by flow cytometry. DNA histograms from flow cytometry of nuclei isolated from FFPE tissue and stained with propidium iodide. X-axis: Fluorescence, proportional to DNA content per nucleus, Y-axis: Number of nuclei. Each histogram is analysed from left to right. The signal to the far left, originates in debris, and is disregarded. The first “real” peak is assumed to originate in diploid nuclei in the G1 phase. Nuclei with twice that fluorescence are assumed to be diploid nuclei in the G2-phase. a) If a mixture of nuclei from a HM and from maternal decidua in the same FFPE block shows this pattern, it indicates that the HM is diploid (DNA content in HM and maternal nuclei being identical). b) If flow cytometry of a mixture of nuclei from a HM and maternal decidua in addition shows a peak midway between the diploid G1 and diploid G2 peaks, it is assumed that this originate in nuclei from a triploid HM. To make this analysis sensitive, it is important that nuclei from maternal decidua do not out-number nuclei from the HM, or vice versa Ploidy analysis by chromogenic and fluorescence in situ hybridization (CISH/FISH). a), c), e) Diploid conceptus showing two signals with probes for chromosome 17 (CISH) and chromosomes X, 7 and 17 (FISH). b), d), f) Triploid conceptus showing three signals for chromosome 17 (CISH) and for sex chromosomes (XXY), 7 and 17 (FISH). These results, interpreted together with morphological features, may support the diagnosis of CHM and PHM, respectively Short tandem repeat genotyping of molar and non-molar pregnancies. Genotypes from villous tissue are presented in the upper panels, with the matched maternal sample in the lower panels. a) In a non-molar pregnancy, at each locus one maternal (pink arrowhead) and one non-maternal (i.e. paternal) (blue arrowhead) allele are present with approximately equal heights. b) PHMs most often contain two paternal and one maternal genomes, which can be identified as a 2:1 ratio of paternal:maternal peak heights or two distinct paternal alleles and one maternal allele. c) Only non-maternal alleles are present in typical CHMs and the majority of cases are homozygous (one allele at each locus). The X axis represents DNA fragment size, with allele name detailed beneath each peak. The Y axis represents arbitrary units of fluorescence. Representative results from three loci (grey bars) are shown. Black arrowheads indicate alleles for which the origin could not be determined Androgenetic/biparental mosaicism. There is strong positive expression of p57 in cytotrophoblasts and p57 negativity in stroma. a), b) Laser capture microdissection of p57 positive cytotrophoblast cells and analysis of short tandem repeats, shows alleles consistent with a diploid complement. c), d) On the other hand, the p57 negative stromal cells have a single allele at all loci tested, consistent with homozygous androgenetic diploidy (both complements originating from one spermatozoon). e), f) Results were compared with DNA extracted from maternal decidua Differential diagnosis of hydatidiform moles a) Hydropic abortion showing villi with hydropic change, but these are small and ballon-like, don’t have cisterns, and trophoblast is attenuated. b) Ectopic tubal pregnancy showing prominent trophoblastic proliferation in very early non-molar conception, without atypia and some polar distribution. c) Non-molar abortion with dysmorphic features showing synciotrophoblast hyperplasia with prominent sprouts projecting into the intervillous space. d), e), f) An unusual case of a trisomic miscarriage (49,XX,+7,+16,+22) with villous enlargement and scalloping, trophoblastic pseudoinclusions and focal trophoblast hyperplasia Differential diagnosis of hydatidiform moles: placental mesenchymal dysplasia. a) Mixture of enlarged and normal-sized villi. b) Distal villi have abnormal hypercellular stroma and display increased number of capillaries, with a chorangiosis-like appearance. c) Abnormal peripheral thick-walled vasculature is observed in stem villi. d) Proximal stem villi are enlarged with stromal overgrowth, edema and cistern formation; no trophoblast proliferation is observed. e) p57 immunoexpression shows a discordant pattern with absent nuclear expression in villous stromal cells and preserved expression in cytotrophoblast suggesting an androgenetic/biparental mosaic/chimera The original article has been corrected.