F. J. Paradinas

Choriocarcinoma and partial hydatidiform moles

BACKGROUND Partial hydatidiform moles (PMs) rarely require chemotherapy and have never previously been proven to transform into choriocarcinoma, the most malignant form of gestational trophoblastic disease (GTD). Consequently, some have questioned whether women with PMs need human chorionic gonadotropin (hCG) follow-up. Here, we investigate whether PMs can transform into choriocarcinomas. METHODS Patients with a PM who developed a subsequent choriocarcinoma were identified from our GTD database. The histology of both PM and ensuing choriocarcinoma was reviewed and flow cytometry used to verify the triploid status of the PMs. To determine whether the choriocarcinoma arose from the PM, DNA from the PM and choriocarcinoma in each patient was compared using microsatellite polymorphisms. FINDINGS Of the 3000 patients with PM, 15 required chemotherapy for persisting GTD. This was identified as choriocarcinoma in three cases. In one patient, the local pathologist could not differentiate between a PM or a hydropic abortion and neither central histological review nor hCG follow-up were obtained. This patient nearly died before the diagnosis of choriocarcinoma was made. Fortunately, the local pathologists correctly diagnosed PM in the two other patients who were then registered for hCG follow-up. Some months later, the hCG was rising and repeat uterine evacuation revealed choriocarcinoma. The PM was confirmed to be triploid in all three cases and genetic analysis showed that the subsequent choriocarcinomas contained identical single maternal and two paternal alleles at several independent loci. INTERPRETATION Our results show that PMs can transform into choriocarcinoma. All patients with suspected PM should be reviewed centrally and, if confirmed, need hCG follow-up.

Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles

Pseudo‐partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles

The pathology of the liver in porphyria cutanea tarda

We report the findings in 53 biopsies from 45 patients with porphyria cutanea tarda (PCT). Red autofluorescence and birefringent acicular cytoplasmic inclusions were constant findings in all untreated cases. Autofluorescence occurs in other hepatic porphyrias, but acicular inclusions appear to be specific for PCT; we have seen them in subclinical porphyria and before development of cutaneous symptoms. They are probably uroporphyrins and they tend to disappear during rinsing by water during most staining procedures. We recommend unstained paraffin sections for their demonstration. Liver damage in PCT has features distinct from other liver diseases, including alcoholic liver disease. These include constant but mild periportal siderosis, focal lipofuscin deposition, focal lobular hepatocyte necrosis associated with groups of pigment‐laden macrophages, focal steatosis, marked hepatocyte hyperplasia and the presence of periductal lymphocyte aggregates. The latter have not been previously described in PCT and were present in 43 % of our cases. There is a direct relationship between increasing age and progressive distortion of liver architecture, with fibrosis present at a mean age of 48 years, cirrhosis at 57 and hepatocellular carcinoma at 66. The characteristic liver histology and the natural history of PCT are against this being the result of any non‐specific liver damage and favour instead a specific liver disease whose pathogenesis may be mainly the result of the metabolic defect of PCT.

Placental site trophoblastic tumour (trophoblastic pseudotumour): a study of four cases requiring hysterectomy including one fatal case.

The clinico‐pathological features of four patients with placental‐site trophoblastic tumour (trophoblastic pseudotumour) are presented. One patient had the nephrotic syndrome associated with evidence of disseminated intravascular coagulation, with complete resolution after hysterectomy. In two patients the tumour extended beyond the uterus, and one of them died with many metastases in spite of intensive post‐operative chemotherapy and ‘second look’ laparotomy. In three patients the tumour behaved as an actively infiltrative neoplasm resistant to chemotherapeutic regimes usually effective for choriocarcinoma. Serum HCG levels were relatively low compared with those of choriocarcinoma. Histologically the tumours were predominantly composed of mononuclear cells supported by a variable amount of vascular stroma and lacked the bilaminar structure characteristic of choriocarcinoma. Scattered cells stained positively with anti‐βHCG and anti‐αHCG antisera. Prior curettage was diagnostic in two of three cases. We did not find a clear correlation between mitotic activity and subsequent behaviour. Inflammatory cell infiltration and evidence of organisation around the tumour may be favourable prognostic indicators. We agree with a recent publication stressing the variable behaviour of this tumour, and emphasize the importance of serum HCG monitoring. Total surgical excision is usually feasible and in aggressive cases offers the best chance of eradication. We support the recent suggestion that ‘trophoblastic pseudotumour’ is an unsuitable name for a potentially lethal disease.

Cholangiocarcinoma coexisting with developmental liver cysts: a distinct entity different from liver cystadenocarcinoma

We report one liver cystadenocarcinoma and two cholangiocarcinomas coexisting with developmental liver cysts. The cystadenocarcinoma was a solitary multilocular cyst with histological features similar to those seen in ovarian mucinous cystadenocarcinoma. In contrast, the other two tumours were a mixture of solid adenocarcinoma and multiple non‐neoplastic cysts containing serous fluid and lined mainly by atrophic epithelium. In both these cases renal cysts were also present and in one case there was focal malignant change of the epithelium lining the cysts from which the solid adenocarcinoma could have originated. Our observations support the view that cholangiocarcinoma associated with developmental liver cysts is an entity different from liver cystadenocarcinoma.

Diploid hydatidiform moles with fetal red blood cells in molar villi. 1--Pathology, incidence, and prognosis.

It is believed that fetal development does not occur in complete mole (CM); when present, it is usually interpreted as proof of partial mole (PM), in most cases a triploid conception with a low incidence of persistent trophoblastic disease (PTD). However, histological examination of 3180 moles in 8 years showed 60 moles (1·8 per cent) with features of CM and either embryonic tissues or amnion in the sample. Flow cytometry (FC) in 40 showed diploid complement in all. In ten of the 40, there was evidence of a twin; in 17, there was only amnion, which could belong to a twin; in the remaining 13, there was no evidence of a twin and nucleated fetal red blood cells (FRCs) were seen within molar vessels in ten (0·3 per cent). Seven of the 40 patients (17·5 per cent) and one of the ten with FRCs in villi (10 per cent) developed PTD, an incidence comparable to that of CM. Genetic studies in seven of these ten are reported separately. Finding fetal tissues with a mole or FRCs in molar vessels is not enough to classify it as PM, since it can be a CM with a twin, fetal development in CM, or possibly a third type of mole. These rare diploid moles with fetal tissues have histological appearances and prognosis similar to those of CM.

Diploid hydatidiform moles with fetal red blood cells in molar villi. 2—genetics

The purpose of this study was to determine the genetic origin of a series of seven diploid hydatidiform moles with fetal red blood cells in the molar villi, normally a characteristic feature of triploid, partial hydatidiform moles. DNA was prepared from formalin‐fixed, paraffin‐embedded blocks of molar tissue and blood from the patient and her partner. The genetic origin of molar tissue was determined by comparing microsatellite polymorphisms in molar and parental tissue following polymerase chain reaction (PCR) amplification of DNA. In six cases, the hydatidiform mole was shown to be androgenetic in origin and therefore genetically to be a complete hydatidiform mole. In one case, the hydatidiform mole was of biparental origin, having both a maternal and a paternal contribution to the genome. We conclude that fetal red blood cells may be observed in the villi of complete hydatidiform moles. In cases where the degree of trophoblastic hyperplasia and ploidy is suggestive of a complete hydatidiform mole, the presence of fetal red blood cells alone should not be considered indicative of a diagnosis of partial hydatidiform mole.

Previous hydatidiform mole identified as the causative pregnancy of choriocarcinoma following birth of normal twins

&NA; For appropriate clinical management of patients with gestational trophoblastic tumors it is important to ascertain both the nature of the causative pregnancy and the time interval between that pregnancy and the diagnosis of the tumor. It has been shown that the immediately antecedent pregnancy may not be the causative pregnancy in some cases of choriocarcinoma, particularly where there is a history of molar pregnancy. We report further studies of a case where the causative pregnancy was shown to be a hydatidiform mole, not the immediately antecedent normal term pregnancy. We describe the use of the polymerase chain reaction (PCR) to amplify short tandem repeat polymorphisms in DNA prepared from pathologic blocks of the patients previously recognised molar pregnancy. A comparison of these polymorphisms with those in the parental and tumor DNA has enabled us to confirm that this hydatidiform mole was indeed the causative pregnancy. Molecular genetic techniques provide a rapid method of determining whether a choriocarcinoma is gestational and, if so, identifying the causative pregnancy.

Significance of the ‘maturation’ of metastases from germ cell tumours after intensive chemotherapy

A comparison between primary and metastatic germ cell tumours from 38 male patients showed that 19 of 24 metastases with residual differentiated teratoma after adequate therapy came from tumours with teratoma as a component of the primary. The correlation between the presence of teratoma in the primary and the metastases is statistically significant (P < 0.01) and supports the view that the so called ‘maturation’ of germ cell tumours is due to selective destruction of anaplastic components in tumours which have already shown an inherent capacity for differentiation. Elevation of the serum concentrations of HCG and AFP on presentation with disseminated disease was significantly related to the presence of morphologically identifiable trophoblast and yolk sac elements respectively in the primary tumours (P < 0.001). Histological identification and specific mention of teratomatous, trophoblastic and yolk sac elements in reporting germ cell tumours is therefore useful since their presence in the primary correlates with the morphology in the metastases.

Amniotic tissue in complete hydatidiform moles can be androgenetic

The purpose of this study was to determine whether amniotic tissue found associated with cases of complete hydatidiform mole (CM) was genetically identical to the CM, and therefore part of the molar pregnancy, or genetically dissimilar to the CM, suggesting derivation from a twin pregnancy. DNA was prepared from formalin‐fixed, paraffin‐embedded blocks of tissue containing both CM and amnion. Maternal DNA was prepared from decidual tissue in the same blocks, or from a maternal blood sample. Fluorescent microsatellite genotyping was carried out to determine the origin of both the CM and the amniotic tissue. In one of six cases examined, the amniotic tissue was genetically different from the CM and was therefore likely to be derived from a twin pregnancy. In the five remaining cases, the amniotic tissue was genetically identical to the CM and was likely to be derived from the same conceptus. It is concluded that androgenetic CM can support the development of amniotic tissue and that some early embryonic development may occur in CM. The presence of amnion, or other fetal tissues, associated with molar tissue should not therefore always be considered indicative of a diagnosis of partial mole (PM). Copyright