Iain Lindsay

Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center

To examine the accuracy of sonographic findings of routine ultrasound examinations in patients with a proven histological diagnosis of complete or partial hydatidiform mole referred to a supra‐regional referral center, and to examine the relationship of sonographic findings to gestational age across the first and early second trimesters.

Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE)

OBJECTIVES To evaluate the efficacy and toxicity of paclitaxel and cisplatin alternating with paclitaxel and etoposide doublet regimen (TP/TE), for salvage of patients with high-risk gestational trophoblastic neoplasia (GTN). PATIENTS AND METHODS Twenty-four patients with GTN received TP/TE. Sixteen had failed previous chemotherapy including six with cisplatin-based regimens (group A) and eight changed to TP/TE because of prior treatment-induced toxic effects (group B). RESULTS In group A, three patients (19%) achieved a complete response (CR) and five (31%) a partial response (PR). All CR and four PR patients remain alive with a median follow-up of 25 months (range 9-48). The eight patients failing TP/TE subsequently died. Thus, the overall survival of the 16 patients in group A was 44% (seven of 16), rising to 70% (seven of 10) if the six patients who had failed prior cisplatin-based chemotherapy were excluded. In group B, four patients were assessable for response (two CR, two PR) and six remain alive (median follow-up 19 months) giving an overall survival of 75%. TP/TE was well tolerated, with only one patient discontinuing therapy because of toxic effects. CONCLUSION TP/TE is an effective, well-tolerated, salvage treatment for relapsed patients who are heavily pretreated for GTN. Further studies of this regimen are warranted.

INTRAPLACENTAL CHORIOCARCINOMA: EXPERIENCE FROM A TERTIARY REFERRAL CENTER AND RELATIONSHIP WITH INFANTILE CHORIOCARCINOMA

The development of persistent gestational trophoblastic disease following an apparently uncomplicated term pregnancy is well-recognized; however, reports of confirmed intraplacental choriocarcinoma are rare. We report four cases of histologically reviewed intraplacental choriocarcinoma occurring in third-trimester pregnancies from the files of a regional trophoblastic disease unit. In all cases, macroscopic examination of the placenta appeared unremarkable, with small nondescript lesions being identified, thought to be fresh infarcts or intervillus thrombi. Histological examination demonstrated the presence of focal intraplacental choriocarcinoma. Review of the literature demonstrates primary intraplacental choriocarcinoma rarely may be associated with obstetric complications such as intrauterine death or fetal distress. But in most cases, the disease is initially asymptomatic, the diagnosis only being made following histopathological placental examination for other indications. Intraplacental choriocarcinoma may therefore manifest as a spectrum of clinical disease ranging from an incidental lesion diagnosed on placental pathological examination with no adverse effects on mother or baby, through to metastatic maternal disease that is present in about half of the cases, to disseminated fatal infantile choriocarcinoma.

Overdiagnosis of complete and partial hydatidiform mole in tubal ectopic pregnancies.

Partial or complete hydatidiform mole (HM) affects approximately 1 in 500 to 1,000 pregnancies. Previous small series suggest that histopathologic diagnosis of HM may be difficult in tubal ectopic pregnancies. The histopathology database of a regional Trophoblastic Disease Unit was searched to identify cases with a referral diagnosis of tubal HM, and the histopathologic findings were reviewed. During the study period (1986-2004 inclusive), there were 132 cases. After central review by specialist histopathologists, the final diagnosis was ectopic partial mole in two, ectopic complete mole in five, and ectopic hydatidiform mole (not otherwise specified) in one. The final diagnosis of definite hydatidiform mole was made in eight (6%) cases, significantly less than in referred uterine curettage specimens, in which approximately 90% have a confirmatory diagnosis of HM (Z = 12.9; p < 0.0001). No cases in this series developed persistent gestational trophoblastic disease, the human chorionic gonadotropin concentration spontaneously returning to normal. Ectopic pregnancies, where managed surgically, should be submitted for histopathologic examination; however, the pathologist should be aware that the degree of extravillus trophoblastic proliferation may appear more florid compared with evacuated uterine products of conception. Molar pregnancy should only be diagnosed when strict criteria regarding morphologic abnormalities previously described in uterine evacuation material are applied.

Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination

The majority of partial (PHM) and complete (CHM) hydatidiform moles are diagnosed in early pregnancy. About half are identified as molar on ultrasonographic examination prior to evacuation. It is uncertain whether unsuspected cases represent an intrinsically different molar phenotype or are simply dependant on sonographer expertise. We measured a microscopic parameter, average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non‐detection on ultrasound.

CURRENT ISSUES IN THE HISTOPATHOLOGY OF GESTATIONAL TROPHOBLASTIC TUMORS

Gestational trophoblastic neoplasia (GTN) encompasses several entities including complete (CHM) and partial (PHM) hydatidiform mole (HM) and the malignant gestational trophoblastic tumors (GTTs), choriocarcinoma (CC), and placental-site trophoblastic tumor (PSTT), including epithelioid trophoblastic tumor (ETT). To detect pGTN, postmolar surveillance by measurement of maternal human chorionic gonoadotropin (hCG) levels should be performed. With such a protocol, many cases of pGTN are identified early at a presymptomatic stage based on plateuing or rising hCG concentrations and subsequently treated successfully with chemotherapy. In such cases, histopathological confirmation of the precise nature of the pGTN usually is not available. However, GTT also may present clinically with primary or metastatic disease, either following and unrecognized HM or developing from a nonmolar gestation. Due to their distinctive clinical and histological features, malignant GTTs are generally clearly subdivided into CC and PSTT (including ETT). CC essentially represents malignant trophoblastic tumors with differentiation toward villous trophoblast, with extensive hematogenous spread and high hCG levels, which are highly chemoresponsive. However, PSTTs, represent malignant differentiation toward implantation-site type trophoblast, with lower hCG levels and less response to chemotherapy. Current issues regarding the clinical and histological features of CC and PSTT/ETT are discussed.

Case report: Malignant teratoma of the uterine corpus

BackgroundTeratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix.Case PresentationWe report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection.ConclusionIn this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.

Placental site trophoblastic tumour derived from an oocyte donation pregnancy

Eleven years after developing idiopathic ovarian failure in herearly twenties, a 32-year-old woman underwent in vitro fer-tilisation (IVF) in which her partner was the sperm donor andher own sister the oocyte donor. This treatment resulted inthe delivery of a healthy girl in January 2004. However, 12months later, she presented to her GP with left iliac fossa painand a positive home pregnancy test.Assessment by the local gynaecology team demonstrateda serum human chorionic gonadotrophin (hCG) level varyingbetween 190 and 260 iu/l, while an ultrasound demonstrateda 2-cm uterine mass, which was initially thought to be afibroid. After further investigations demonstrated a rise inthe hCG level, a laparoscopy and dilatation and curettagewere performed.Histopathological examination demonstrated fragments ofendometrium and myometrium with infiltration of the myo-metrium by sheets of mitotically active cells with eosinophiliccytoplasm and ovoid nuclei highly suggestive of the diagnosisof placental site trophoblastic tumour (PSTT) (Figure 1).At this point, she was referred to Charing Cross Hospital,London, one of the national centres in the UK for treatmentof trophoblastic tumours. Updated investigations demon-strated the hCG level to remain elevated at 111 iu/l. A pelvicDoppler ultrasound confirmed the presence of a 3-cm mass oflow vascularity, while pelvic magnetic resonance imaging anda computed tomography (CT) of the chest and abdomen didnot show any evidence of distant spread.Following investigations, she was treated surgically witha hysterectomy plus bilateral salpingo-oophorectomy. Thepathology confirmed the diagnosis of PSTT confined tothe uterus, although malignant cells were found adjacent tothe serosal surface.Fluorescent microsatellite genotyping was performed onDNA from tumour cells obtained by microdissection offormalin-fixed, paraffin-embedded sections and from bloodsamples from the patient, her partner and sister. The genotypeof the tumour was disomic, with one allele from the partnerand one from the patient’s sister for five informative alleles(Table 1). No maternal alleles was identified at any informa-tive loci.Postoperatively, the hCG level fell to normal. However, asmalignant cells were present at the serosal resection surface,she received 8 weeks of adjuvant chemotherapy using thepaclitaxel/etoposide paclitaxel/cisplatin regimen.