3q26 Gene Amplification in a Woman With Abnormal Cervical Cytology Unconfirmed by Cervical Biopsies

CLINICAL HISTORY Patient: A 28-year-old Caucasian female. Chief Complaint: Multiple abnormal Pap tests unconfirmed by cervical and endocervical biopsies. History of Present Illness (see Table 1): In 2008 the patient was diagnosed with a low-grade squamous intraepithelial lesion (LSIL) by Thin Prep Papanicolaou test (Pap test). Over the next 2.5 years, multiple Thin Prep Pap assessments showed increasing severity of cellular changes from "atypical squamous cells cannot exclude HSIL (ASC-H)" to "high-grade squamous intraepithelial lesion (HSIL)" (Image 1). During this period 4 successive cervical biopsies and endocervical curettings, however, revealed only benign squamous mucosa, squamous metaplasia, reactive squamous atypia, and benign endocervix. The only exception was a small number of cells suspicious for a squamous intraepithelial lesion (SIL) (dysplasia) present in the endocervical curettings performed in May 2010. Multiple tests performed during these 2.5 years were positive for high-risk human papillomavirus (HPV). From February 2009 to January 2011, 4 colposcopic examinations, done at 6-month intervals, showed an area of acetowhite epithelium at the 11-12 o'clock position of the cervix. The colposcopies were judged to be satisfactory with complete visualization of the cervical-endocervical transition zone. In June 2011 an automated fluorescense in situ hybridization (FISH) assay for detection of 3q gain in HPV infected cervical cells (oncoFISH cervical test, Ikonisys Clinical Laboratory, New Haven, CT) was positive, showing 2 nuclei with at least 5 copies of 3q26 (Image 2). Two months later a cervical loop electrosurgical excision procedure (LEEP), encompassing the acetowhite epithelium and surrounding tissue, was performed. Histological examination revealed a very small focus of cervical intraepithelial neoplasia grade 3 (CIN 3) at the end of the endocervical margin of the transition zone with involvement of a single endocervical gland. The lesion appeared to be completely excised. Medical History: Oral contraceptive use; no smoking; no abnormal bleeding; no previous gynecology surgery.