Correspondence

Volume 162 Number 6

drome in the first trimester. AM J OBSTET GYNECOL 1989; 160: 1194-6). Repeated ultrasonographic evaluation failed to reveal any sign of fetal congestive heart failure. Thus, the cord hemoglobin was 8.5 mg/dl at delivery and the infant died 3 days after birth. Unfortunately, the cause of death was not given. In accordance with the range of fetal hemoglobin concentration, I this fetus suffered from moderate anemia. Van Allan et al.! who reported the largest series of reversed arterial perfusion syndrome, noted that the main cause of morbidity and mortality of the pumping twin was congestive heart failure. Failure of ultra sonographic parameters to predict the severity of the anemia in rhesus isoimmunization was recently reported and fetal blood sampling was suggested in these cases.' In light of this information we suggest that blood sampling of the pumping fetus should be taken and blood transfusion should be performed in utero if indicated to prevent fetal anemia and congestive heart failure. P.Jakobi, MD E. Z. Zimmer, MD Department of Obstetrics and Gynecology "B" Rambam Medical Center Bat-Galim POB 9602 Haifa, Israel 31086 REFERENCES l. Nicolaides KH, Clewell WH, Mibashan RS, Sooth ill PW,

Rodeck CH, Cambell S. Fetal haemoglobin measurements in the assessment of red cell isoimmunization. Lancet 1988; 1: 1073-5. 2. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol 1983;7:28593. 3. Nicolaides KH, Fontanarosa M, Gabbe SG, Rodeck CH. Failure of ultrasonographic parameters to predict the severity of fetal anemia in rhesus isoimmunization. AM JOBSTET GYNECOL 1988;158:920-6.

Reply To the Editors: We appreciate the comments related to our article. It was suggested that fetal blood sampling be performed in the pump twin to assess for fetal anemia, with intrauterine transfusions to be performed if needed. Unfortunately, little information exists in the literature as to the incidence of fetal anemia in twin reversed arterial perfusion pump babies. In the Van Allen et al. series of 14 pregnancies complicated by twin reversed arterial perfusion, no hemoglobin information is available. I A central question is whether the congestive heart failure that often occurs in pump fetuses is a result of the cardiovascular demands of supporting two circulations or whether it is a result of anemia. Given the limited information concerning the fetal cardiovascular hemodynamics of the twin reversed arterial perfusion syndrome, the suggestion to perform

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fetal blood sampling is not unreasonable. It is hoped that further studies will document the value or lack there of in the management of this problem. Robert J. Stiller, MD Roberto Romero, MD Department of Obstetrics and Gynecology Yale University School of Medicine 333 Cedar St. New Haven, CT 06510 REFERENCE 1. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol 1983;7: 285.

Lichen sclerosus, invasive squamous cell carcinoma, and human papillomavirus To the Editors: Invasive squamous cell carcinoma of the vulva appears to arise in association with a coexistent intraepithelial abnormality. I This abnormality usually falls into two main categories, either hyperplastic dystrophy, associated with lichen sclerosus in most cases, or severe atypia grade 3 (vulvar intraepithelial neoplasia). Controversy exists over the malignant potential of lichen sclerosus, with studies demonstrating the coexistence of lichen sclerosus in excision specimens of squamous cell carcinoma ranging from little or no association 2 to 63%.' In our own series of 78 cases of squamous cell carcinoma the histologic coexistence with lichen sclerosus was 60%. Conversely, however, in clinical practice this relationship is small as we examine and treat a large number of patients with lichen sclerosus, few of whom subsequently develop a squamous cell carcinoma. 3, 4 This discrepancy may reflect the beneficial effects of treatment as the majority of cases of lichen sclerosus recognized histologically in the squamous cell carcinoma specimens had not been diagnosed or treated previously. Alternatively, the difference may indicate the prerequisite of a cofactor such as concurrent infection with human papillomavirus (HPV). To test this hypothesis we analyze 10 cases of squamous cell carcinoma with coexistent lichen sclerosus to determine the presence of HPV. The technique used for detection of the virus was Southern blot hybridization under stringent conditions. Table I indicates the probes used and the results. The negative findings suggest either that the viral deoxyribonucleic acid tested was not present or that insufficient total deoxyribonucleic acid was available for detection in the tissues sampled. The latter explanation seems unlikely as we had conducted simultaneously an analysis with the same technique on 10 cases of squamous cell carcinoma with evidence of grade 3 vulvar intraepithelial neoplasia; we obtained positive results in seven of the II lesions (Lessana-Leibowitch M. Unpublished data), and in six of seven HPV # 16 was detected.

1634 Correspondence

June 1990 Am J Obstet Gynecol

Table I. HPV deoxyribonucleic acid sequences in squamous cell carcinoma of vulva with coexistent lichen sclerosus Probe

Detection

HPV 16 HPV 18 HPV 31 HPV 33 HPV*

0110 0110 0110 0110 0110

*Undetermined type.

A recent study of five cases of uncomplicated lichen sclerosus failed to demonstrate the presence of HPV.' These preliminary results suggest that HPV is not implicated in the etiology of lichen sclerosus or in the induction of malignant change in this disorder. S. M. Neill, MD Westminster Hospital Department of Dermatology Horseferry Road London, England SWIP 2AP M. Lessana-Leibowitch, MD M. Pelisse, MD M. Moyal-Barracco, MD

Hopital Tarnier-Cochin Service de Dermatologie 89 Rue d'Assas F. 75006 Paris, France The Southern blotting was kindly performed in the virology laboratory of the Pasteur Institute, Paris, under the supervision of Professeur Gerard Orth.

REFERENCES I. Zaino RJ, Husseinzadeh N, Nahhas W, Mortel R. Epithelial

2. 3. 4. 5.

alterations in proximity to invasive squamous carcinoma of the vulva. Int J Gynecol Pathol 1982; I: 173-84. Hart RW, Norris HJ, Helwig E. Relation oflichen sclerosus et atrophicus of the vulva to development of carcinoma. Obstet Gynecol 1975;45:369-77. Wallace HJ. Liehen sclerosus et atrophicus. Trans StJohns Hosp Dermatol Soc 1971;57:9-30. Kaufman RH, Gardner HL, Brown D Jr, Beyth Y. Vulvar dystrophies: an evaluation. AM J OBSTET GYNECOL 1974; 120:363-7. Karram M, Tabor B, Smotkin D, Wettstein F, Bhatia N, Micha J. Detection of human papilloma virus deoxyribonucleic acid from vulvar dystrophies and vulvar intraepithelial neoplastic lesions. AM J OBSTET GYNECOL 1988; 159:22-3.

Measurement of unconjugated estriol by enzyme-linked immunosorbent assay fails to show an association with Down syndrome To the Editors:

Canick et al. l and subsequently Wald et aU have reported on the use of unconjugated estriol as a marker for Down syndrome in a protocol of prenatal maternal serum screening. Their reports indicate that maternal

Table I. Levels of unconjugated estriol in 27 cases of trisomy 21 Rank I

2

3 4 5 6

7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

Gestational age (wh)

MoM

18 18 16 17 15 15 15 17 14 16 16 16 17 15 15 16 18 15 16 18 16 16 16 16 15 16 16

0.4 0.4 0.64 0.64 0.68 0.68 0.69 0.8 0.82 0.86 0.87 0.95 1.04 1.09 1.1 1.15 1.15 1.16

1.39 1.51 1.82 2.31 2.47 2.57 2.8 2.94 3.79

Table II. Percent of Down syndrome cases and controls with maternal serum unconjugated estriol levels less than or equal to given MoM levels Unconjugated estriol level (MoM)

Down syndrome cases

Controls

(%)

(%)

sO.50 sO.65 sO.80 sl.OO

7.4 14.8 29.6 44.4

4.7 19.4 36.5 51.3

serum levels of unconjugated estriol are significantly lower in pregnancies affected by Down syndrome than in matched controls. Any marker that adds to detection efficiency in prenatal Down syndrome screening, would be particularly welcome. The poor performance of maternal serum a-fetoprotein as a marker for Down syndrome has been reported."·5 Our first evaluation 6 of unconjugated estriol used the same radioimmunoassay reagents and procedure (modified per Canick et al. l and Wald et al. 2 ), but did not show the utility of this marker. No significant difference was found in the level of unconjugated estriol between controls and pregnancies affected by Down syndrome. We have completed a further study of unconjugated estriol with the use of a different method of measure-