A large cohort of rhesus‐negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti‐D immunoglobulin in 1977–8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age‐ and parity‐matched control group of rhesus‐positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme‐linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV‐RNA‐positive (type 1b) on PCR testing. In the 20 years post‐infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR‐positive women. Of the children born to HCV‐RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV‐RNA‐positive mothers apart from one single exception in the antibody‐positive HCV‐RNA‐negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

Recurrent miscarriage

10.1093/qjmed/93.9.597

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Human papillomavirus and mixed epithelial tumors of the endometrium

Human Pathology (1998)

John O’Leary R J Landers Mary Crowley Irene Healy Maria O’Donovan

Strong epidemiological evidence links human papilloma viruses (HPV) with the development of cervical intraepithelial neoplasia (CIN) and invasive cancers of the uterine cervix. The localization of HPV DNA sequences high up in the female genital tract (in benign and malignant lesions) is not that uncommon, but its precise significance is uncertain. In particular, the detection of HPV DNA sequences by polymerase chain reaction (PCR) needs careful interpretation, because the source of the amplicon may emanate from tumor cells, direct contamination from the cervix, or possibly from extratumoral sites in the endometrium. We have previously reported the identification of koilocyte-like changes in the squamous epithelium of some endometrial adenoacanthomas. Adenoacanthomas (adenocarcinoma with squamous metaplasia) are mixed epithelial tumors arising in the endometrium composed of malignant glandular areas admixed with benign metaplastic squamous epithelium. The rarer adenosquamous carcinoma containing both malignant glandular and squamous areas is also described. The origin of benign/malignant squamous epithelial islands in endometrial tumors has been the subject of speculation, with some investigators considering an origin from metaplastic glandular endometrial cells. In this study, we examined 10 normal endometrial samples, 20 adenocarcinomas, 41 adenocarcinomas with squamous metaplasia, and two adenosquamous carcinomas, (including control cervical material where possible) for the presence of HPV DNA sequences using nonisotopic in situ hybridization (NISH), type-specific HPV PCR, general primer PCR (to detect sequenced and unsequenced HPVs), and PCR in situ hybridization (PCR-ISH). We did not identify HPV DNA sequences in normal endometrial tissue. In adenocarcinomas (endometrioid type), HPV was only identified in 2 of 20 cases by PCR, both of which were HPV 11 positive. We were unsuccessful in identifying HPV in endometrial carcinomas by NISH or by PCR-ISH, raising the possibility of contamination from the cervix in the two positive cases. In adenoacanthomas, a low-risk HPV type (HPV 6) was found in 19 of 41 cases. NISH signals were intranuclear in location in squamous regions of adenoacanthomas. Additional positive nuclei were uncovered using PCR-ISH, which increases the sensitivity of standard NISH detection. HPV DNA sequences were located in some malignant endometrial glandular epithelial cells, but this accounted for a minority of samples. HPV DNA sequences were not detected in extraepithelial sites. Mixed infection by two different HPV types was identified in two cases. Most cases showed similar HPV types in cervical and endometrial lesions, although discordant cases were uncovered. In adenosquamous carcinomas, one case showed mixed infection with HPV 6 and 33 by PCR. The apparent segregation of low-risk HPV type (HPV 6) with benign squamous metaplastic epithelium in adenocarcinoma with squamous metaplasia, and high-risk type (HPV 33) with malignant squamous epithelium in adenosquamous carcinoma, raises important questions in relation to the role of HPVs in mixed epithelial tumors of the endometrium and their interplay in the pathogenesis of squamous metaplasia at extracervical sites.

Adenosquamous carcinoma

Squamous metaplasia

Squamous carcinoma

10.1016/s0046-8177(98)90120-4

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Hodgkin's Lymphoma With Digital Clubbing

Journal of Clinical Oncology (2009)

Matthew Goodyer Marie-Claire Cronin Dawn G. Ketsitlile Séamus O’Reilly Eugene Moylan

10.1200/jco.2008.21.7323

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Citations (14)