Cytomegalovirus Endocervicitis Diagnosed by Cervical Smear Kent Gideon, M.D., and Paul Zaharopoulos,
M.D.
Cytomegalovirus (CMV) cytologic changes were found in a routine cervicalsmear of a 21-yr-old HIV-negative woman, 4 w k post partum. The CMV changes were associated with columnar cervical epithelium. The case is reported because of the rarity of such an occurrence in cervicalsmears. Diagn Cytopathol 1991;7:625621.
good health. The mother's post partum clinical course was uncomplicated, and she was found to be in good health 3 mo later, at which time repeat cervical cytology was performed. HIV serology was negative.
Key Words: Cytology; Columnar cervical epithelium; Post partum; HIV negative
The original cervical smear contained numerous large cells with large, dark intranuclear inclusions (single or double) surrounded by clear haloes and chromatin marginated peripherally near the nuclear envelope. These cells had ample cytoplasm with multiple, granular cytoplasmic inclusions. They were singly arranged, associated with columnar cervical cells, and within sheets of columnar epithelium (Figs. 1-3). Mild dysplastic changes with koilocytosis, suggestive of human papilloma virus infection, were also observed. The cervical smear obtained 3 mo post partum did not contain identifiable CMV changes.
Cytomegalovirus (CMV) inclusion disease has been rarely reported in the uterine cervix. Of the reported cases, most were confirmed by viral culture, serology, and/or endocervical biopsy. Only two cases of CMV of the cervix, diagnosed by routine cervical smear, have been reported. We report the case of an otherwise healthy, human immunodeficiency virus (H1V)-negative, woman with CMV cervicitis diagnosed by cervical smear 4 wk post partum. 'y2s3
Materials and Methods Case Report
Discussion
A 21-yr-old woman was seen on a routine 4-wk post partum visit during which a cervical cytology smear was obtained. Her prenatal course was unremarkable except for prolonged rupture of the membranes and failure of labor to progress, which necessitated a primary Caesarian section. Histologic examination of the fetal membranes and placenta revealed an acute chorioamnionitis consistent with bacterial type. Immunoperoxidase stains and DNA hybridization for CMV of the placenta and fetal membranes performed after the post partum smear was examined, were negative. The newborn developed pneumonia which responded to antibiotics and was released in ~~~~
Received January 13, 1991. Accepted July 19, 1991. From the Division of Cytopathology, The University of Texas Medical Branch, Galveston, TX. Address reprint requests to Paul Zaharopoulos, M.D., Director, Division of Cytopathology, Route E48, The University of Texas Medical Branch, 30 1 University, Galveston, TX 77550.
0 1991 WILEY-LISS. INC.
Results
Cytomegalovirus, one of the herpes viruses, is known to cause a variety of clinical syndromes in children and adults. Exposure to and infection by CMV are quite common, whereas actual clinical manifestations of the disease are somewhat infrequent. The incidence of serum antibodies to CMV has been reported as high as 40-100% of the general population by some authors. There are two age peaks during which the infection is most common. The first peak occurs during the perinatal period, and the second is in early adulthood. Most recently, the disease has received notoriety due to its frequent association with the acquired immunodeficiency syndrome (AIDS). In the immunocompetent host, however, the primary infection usually goes unnoticed. It has been suggested by certain investigators2 that recently acquired human papilloma virus (HPV) infection as manifested by extensive condylomatous involvement of the vulva and cervix is associated with increased incidence of CMV infection. The reason for this relationship is not
Diagnostic Cytopathology, Vol 7, No 6
625
GIDEON AND ZAHAROPOULOS
Fig. 1. (A) Cytomegaloviral inclusion changes in cervical cells. (B) Attached columnar cervical cells (Papanicolaou, x 500).
understood. In the case we presently report, there were HPV-associated changes (mild dysplasia of squamous epithelium with koilocytosis) in the cervical smear, but no gross condylomatous involvement of the vaginal canal or vulva. Furthermore, since the original submission of this article we have encountered another case of CMV infection in a cervical smear of an HIV-negative woman with no history of recent pregnancy. This second patient also did not present with gross condylomata in the lower genital tract and additionally lacked cervical HPV-associated cytologic changes. Our limited experience is obviously insufficient to delineate the relationship between these two viral diseases. Transmission of the CMV can occur via several routes. It has been isolated from both semen and uterine cervical secretions; therefore, it is hypothesized that sexual transmission is possible. The offspring is exposed when passing through the birth canal, via the breast milk of infected mothers during nursing, and by direct contact with other infected children. Intrauterine transplacental infection presents still another mode of transmission.
'
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Fig. 2. (A,B) Cervical cells with cytomegalic inclusion changes. Columnar cervical cells are seen attached to the infected cells (Papanicolaou, X 500).
CMV infection is common in the peripartum period, but detection of diagnostic cells in cervical cytologic smears has rarely been reported. In tissue sections of the cervix, however, CMV has been more frequently observed. 5,6,9 Cytomegalic inclusion disease has also been described in the endometrium as well as in fibroblasts and endothelial cells of the uterus5 Morse et al. Cultured CMV from the cervix of 12 out the 186 women they studied, but viral inclusions were only seen in one of the cervical smears. Our case not only demonstrates the presence of CMV in the uterus but also localizes the infection to the cervical columnar epithelium. Because of the severity of CMV infection in neonates and the higher incidence of the disease in pregnant women, a high index of suspicion is necessary for early diagnosis. Routine cervical smears may not be the preferred specimen for diagnosis of uterine CMV infection, but a thorough examination of the patient along with the appropriate use of serologic testing and virologic methods, including cultures, can provide clues to the diagnosis in suspected cases. lo,ll An aware-
*
CMV ENDOCERVICITIS DIAGNOSED BY CERVICAL SMEAR
ness that CMV changes can occasionally be found in cervical smears may also aid in the diagnosis of unsuspected cases.
References
Fig. 3. Columnar cervical epithelium with one cell showing cytomegaloviral inclusion changes (Papanicolaou, x 500).
1. Diosi P, Babusleac L, Nevinglouschi 0, Kun-Stoicu G. Cytomegalovirus infection associated with pregnancy. Lancet 1967; 2:1063. 2. Morse AR, Coleman DV, Gardner SD. An evaluation of cytology in the diagnosis of herpes simplex virus infection and cytomegalovirus infection of the cervix uteri. J Obstet Gynaecol Br Commonwealth 1974;81:393-8. 3. Coleman DV. Cytologic diagnosis of virus-infected cells in cervical smears. Diagn Gynecol Obstet 1982;4:363-74. 4. H o M. Cytomegalovirus. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. New York: John Wiley and Sons, 1985:960-70 and 1159-72. 5. Deppisch LM. Cytomegalovirus inclusion body endocervicitis: significance of CMV inclusions in endocervical biopsies. Mt Sinai J Med 1981;48:418-2 1. 6. Wenckebach GFC, Curry B. Cytomegalovirus infection of the female genital tract. Histologic findings in three cases and review of the literature. Arch Pathol Lab Med 1976;100:609. 7. Lang DJ. Cytomegalovirus infections in pregnancy and the newborn. Clin Obstet Gynecol 1970;13:348-59. 8. Josey YW, Nahmias A, Naib ZM. Viral and virus-like infections of the female genital tract. Clin Obstet Gynecol 1969;12:61. 9. Brown S, Senekjian EK, Montag AG. Cytomegalovirus infection of the uterine cervix in a patient with acquired immunodeficiency syndrome. Obstet Gynecol 1988;71:489. 10. Alford CA, Britt WJ. Cytomegalovirus. In: Fields BN, et al., eds. Virology. New York: Raven Press, 1985:629-60. 11. Booth JC, Hannington G, Bakir TMF, et al. Comparison of enzymelinked immunosorbent assay, radioimmunoassay, complement fixations, anticomplement immunofluorescence and passive hemagglutination techniques for detecting cytomegalovirus IgG antibody. J Clin Pathol 1982;35:1345.
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M.D.
Cytomegalovirus (CMV) cytologic changes were found in a routine cervicalsmear of a 21-yr-old HIV-negative woman, 4 w k post partum. The CMV changes were associated with columnar cervical epithelium. The case is reported because of the rarity of such an occurrence in cervicalsmears. Diagn Cytopathol 1991;7:625621.
good health. The mother's post partum clinical course was uncomplicated, and she was found to be in good health 3 mo later, at which time repeat cervical cytology was performed. HIV serology was negative.
Key Words: Cytology; Columnar cervical epithelium; Post partum; HIV negative
The original cervical smear contained numerous large cells with large, dark intranuclear inclusions (single or double) surrounded by clear haloes and chromatin marginated peripherally near the nuclear envelope. These cells had ample cytoplasm with multiple, granular cytoplasmic inclusions. They were singly arranged, associated with columnar cervical cells, and within sheets of columnar epithelium (Figs. 1-3). Mild dysplastic changes with koilocytosis, suggestive of human papilloma virus infection, were also observed. The cervical smear obtained 3 mo post partum did not contain identifiable CMV changes.
Cytomegalovirus (CMV) inclusion disease has been rarely reported in the uterine cervix. Of the reported cases, most were confirmed by viral culture, serology, and/or endocervical biopsy. Only two cases of CMV of the cervix, diagnosed by routine cervical smear, have been reported. We report the case of an otherwise healthy, human immunodeficiency virus (H1V)-negative, woman with CMV cervicitis diagnosed by cervical smear 4 wk post partum. 'y2s3
Materials and Methods Case Report
Discussion
A 21-yr-old woman was seen on a routine 4-wk post partum visit during which a cervical cytology smear was obtained. Her prenatal course was unremarkable except for prolonged rupture of the membranes and failure of labor to progress, which necessitated a primary Caesarian section. Histologic examination of the fetal membranes and placenta revealed an acute chorioamnionitis consistent with bacterial type. Immunoperoxidase stains and DNA hybridization for CMV of the placenta and fetal membranes performed after the post partum smear was examined, were negative. The newborn developed pneumonia which responded to antibiotics and was released in ~~~~
Received January 13, 1991. Accepted July 19, 1991. From the Division of Cytopathology, The University of Texas Medical Branch, Galveston, TX. Address reprint requests to Paul Zaharopoulos, M.D., Director, Division of Cytopathology, Route E48, The University of Texas Medical Branch, 30 1 University, Galveston, TX 77550.
0 1991 WILEY-LISS. INC.
Results
Cytomegalovirus, one of the herpes viruses, is known to cause a variety of clinical syndromes in children and adults. Exposure to and infection by CMV are quite common, whereas actual clinical manifestations of the disease are somewhat infrequent. The incidence of serum antibodies to CMV has been reported as high as 40-100% of the general population by some authors. There are two age peaks during which the infection is most common. The first peak occurs during the perinatal period, and the second is in early adulthood. Most recently, the disease has received notoriety due to its frequent association with the acquired immunodeficiency syndrome (AIDS). In the immunocompetent host, however, the primary infection usually goes unnoticed. It has been suggested by certain investigators2 that recently acquired human papilloma virus (HPV) infection as manifested by extensive condylomatous involvement of the vulva and cervix is associated with increased incidence of CMV infection. The reason for this relationship is not
Diagnostic Cytopathology, Vol 7, No 6
625
GIDEON AND ZAHAROPOULOS
Fig. 1. (A) Cytomegaloviral inclusion changes in cervical cells. (B) Attached columnar cervical cells (Papanicolaou, x 500).
understood. In the case we presently report, there were HPV-associated changes (mild dysplasia of squamous epithelium with koilocytosis) in the cervical smear, but no gross condylomatous involvement of the vaginal canal or vulva. Furthermore, since the original submission of this article we have encountered another case of CMV infection in a cervical smear of an HIV-negative woman with no history of recent pregnancy. This second patient also did not present with gross condylomata in the lower genital tract and additionally lacked cervical HPV-associated cytologic changes. Our limited experience is obviously insufficient to delineate the relationship between these two viral diseases. Transmission of the CMV can occur via several routes. It has been isolated from both semen and uterine cervical secretions; therefore, it is hypothesized that sexual transmission is possible. The offspring is exposed when passing through the birth canal, via the breast milk of infected mothers during nursing, and by direct contact with other infected children. Intrauterine transplacental infection presents still another mode of transmission.
'
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Diagnostic Cytopathology, Vol % No 6
Fig. 2. (A,B) Cervical cells with cytomegalic inclusion changes. Columnar cervical cells are seen attached to the infected cells (Papanicolaou, X 500).
CMV infection is common in the peripartum period, but detection of diagnostic cells in cervical cytologic smears has rarely been reported. In tissue sections of the cervix, however, CMV has been more frequently observed. 5,6,9 Cytomegalic inclusion disease has also been described in the endometrium as well as in fibroblasts and endothelial cells of the uterus5 Morse et al. Cultured CMV from the cervix of 12 out the 186 women they studied, but viral inclusions were only seen in one of the cervical smears. Our case not only demonstrates the presence of CMV in the uterus but also localizes the infection to the cervical columnar epithelium. Because of the severity of CMV infection in neonates and the higher incidence of the disease in pregnant women, a high index of suspicion is necessary for early diagnosis. Routine cervical smears may not be the preferred specimen for diagnosis of uterine CMV infection, but a thorough examination of the patient along with the appropriate use of serologic testing and virologic methods, including cultures, can provide clues to the diagnosis in suspected cases. lo,ll An aware-
*
CMV ENDOCERVICITIS DIAGNOSED BY CERVICAL SMEAR
ness that CMV changes can occasionally be found in cervical smears may also aid in the diagnosis of unsuspected cases.
References
Fig. 3. Columnar cervical epithelium with one cell showing cytomegaloviral inclusion changes (Papanicolaou, x 500).
1. Diosi P, Babusleac L, Nevinglouschi 0, Kun-Stoicu G. Cytomegalovirus infection associated with pregnancy. Lancet 1967; 2:1063. 2. Morse AR, Coleman DV, Gardner SD. An evaluation of cytology in the diagnosis of herpes simplex virus infection and cytomegalovirus infection of the cervix uteri. J Obstet Gynaecol Br Commonwealth 1974;81:393-8. 3. Coleman DV. Cytologic diagnosis of virus-infected cells in cervical smears. Diagn Gynecol Obstet 1982;4:363-74. 4. H o M. Cytomegalovirus. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. New York: John Wiley and Sons, 1985:960-70 and 1159-72. 5. Deppisch LM. Cytomegalovirus inclusion body endocervicitis: significance of CMV inclusions in endocervical biopsies. Mt Sinai J Med 1981;48:418-2 1. 6. Wenckebach GFC, Curry B. Cytomegalovirus infection of the female genital tract. Histologic findings in three cases and review of the literature. Arch Pathol Lab Med 1976;100:609. 7. Lang DJ. Cytomegalovirus infections in pregnancy and the newborn. Clin Obstet Gynecol 1970;13:348-59. 8. Josey YW, Nahmias A, Naib ZM. Viral and virus-like infections of the female genital tract. Clin Obstet Gynecol 1969;12:61. 9. Brown S, Senekjian EK, Montag AG. Cytomegalovirus infection of the uterine cervix in a patient with acquired immunodeficiency syndrome. Obstet Gynecol 1988;71:489. 10. Alford CA, Britt WJ. Cytomegalovirus. In: Fields BN, et al., eds. Virology. New York: Raven Press, 1985:629-60. 11. Booth JC, Hannington G, Bakir TMF, et al. Comparison of enzymelinked immunosorbent assay, radioimmunoassay, complement fixations, anticomplement immunofluorescence and passive hemagglutination techniques for detecting cytomegalovirus IgG antibody. J Clin Pathol 1982;35:1345.
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