Atypical cytological changes mimicking SIL of the uterine cervix in allogenic hematopoietic stem cell transplantation recipients treated with busulfan

Cancer Cytopathol. 2019 Jun;127(6):399-406. doi: 10.1002/cncy.22148. Epub 2019 May 30.

Abstract

Background: Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a common procedure in hematological disorders and is preceded by a conditioning regimen that usually includes busulfan. The immunosuppression caused by the conditioning regimen and graft-versus-host disease prophylaxis is associated with human papillomavirus (HPV) persistence and, consequently, with an increased risk of cervical cancer (CC) and squamous intraepithelial lesions (SILs)-the precursors of CC. A gynecological check-up that includes CC screening is recommended in these patients.

Methods: All female recipients of allo-HSCT undergo routine gynecological check-up that includes CC screening. Cervical samples were obtained for liquid-based cytology and HPV testing. Cytology smears were stained with the Papanicolaou (Pap) technique. A colposcopy evaluation was performed if any abnormal result in the screening tests was obtained.

Results: Among 15 women undergoing gynecological examination at 1 year after allo-HSCT who had received a conditioning regimen that included busulfan, 4 (26.7%) showed atypical squamous cells in the Pap smear, suggesting high-grade SIL. The abnormalities were identified from 136 to 271 days after allo-HSCT. In all cases, HPV testing was negative, and colposcopy examination was normal. The cytological abnormalities regressed in 3 of the women after 1 year but persisted in 1 woman at day 382 after allo-HSCT.

Conclusions: Treatment-related atypia mimicking SIL is a common finding in allo-HSCT recipients who have received busulfan, particularly in the first year after the procedure. However, atypical changes may persist for more than 1 year. Clinical information, HPV testing, and colposcopy examination are critical to prevent misdiagnosis and overtreatment in these patients.

Keywords: allogenic hematopoietic stem cell transplantation; atypia mimicking squamous intraepithelial lesion; busulfan; cervix; treatment-related atypia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Busulfan / adverse effects*
  • Cervix Uteri / diagnostic imaging
  • Cervix Uteri / drug effects*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Colposcopy
  • Diagnostic Errors / prevention & control
  • False Positive Reactions
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Medical Overuse / prevention & control
  • Middle Aged
  • Myeloablative Agonists / adverse effects*
  • Papanicolaou Test
  • Papillomaviridae / immunology
  • Papillomaviridae / isolation & purification
  • Sensitivity and Specificity
  • Transplantation, Homologous / adverse effects
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / immunology
  • Uterine Cervical Dysplasia / therapy
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / therapy
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears
  • Young Adult

Substances

  • Myeloablative Agonists
  • Busulfan