Menopause Management Knowledge in Post-Graduate Family Medicine, Internal Medicine and Obstetrics & Gynecology Residents: A Cross-Sectional Survey
Objective: Atypical Glandular Cells (AGC) is a rare Pap smear finding that is associated with a high rate of clinically significant disease. Previous research recognized an association between AGC and primary malignancies, but whether each AGC-subclass (Endocervical [EC], Endometrial [EM], or Not Otherwise Specified [NOS]) carries a similar risk of post-AGC invasive cancers has not been assessed. The objective of this study is to assess the risk of invasive cancers associated with Atypical Glandular Cell (AGC) subclasses.
Methods: A prospective case series was designed to identify cases of AGC through the pathology database at The Reading Hospital and Medical Center between 1/1/2005 and 6/1/2017. The AGC pathology report included patient’s age, date of initial AGC Pap, AGC subclass, provider, and cytopathologist recommendations. Additional information including demographics, pathologic and follow-up data was gathered by chart review via the Reading Hospital Electronic Medical Record System. A multivariate survival analysis was conducted using SAS; P<0.05 was deemed as statistically significant. Covariates adjusted in the survival analysis included age, body mass index (BMI), hypertension, diabetes, smoking, dyslipidemia, polycystic ovarian syndrome (PCOS), oral contraceptive use, and intrauterine device (IUD) use.
Results: Of the women diagnosed with AGC between 1/1/2005 and 6/1/2017 (n=656), 641 received at least one follow up visit. Mean (SD, median, min-max) follow up time after AGC diagnosis are 4.7(3.2, 5.2, 0.01-10.4) years. Of the 641 women who received a follow up visit, 397 received an endometrial biopsy and were classified into AGC subclasses AGC-EC (n =81, 20.4%), AGC-EM (n=141, 35.5%), AGC-NOS (n=175, 44.1%), and a total of 91 women (14.2%) were diagnosed with at least one invasive cancer post-AGC diagnosis. The majority of the 91 women had endometrial cancer (n=53), with the number of women diagnosed with breast (n=11), skin (n=9), cervical (n=8), thyroid (n=2), Hodgkin’s lymphoma (n=2), and other (n=6) cancers occurring at lower rates. Cochran-Armitage trend test showed that in the 397 women with endometrial biopsy after AGC diagnosis, the risk of endometrial cancer increased in a stepwise manner across AGC subclasses from AGC-EC, to AGC-NOS, to AGC-EM (p=0.0025). In addition, in the 641 women who received at least one follow up visit after AGC diagnosis, the risk of all invasive cancers increased in a stepwise manner across AGC subclasses from AGC-EC, to AGC-NOS, to AGC-EM (p=0.005). Log Rank test which analyzed time-to-endometrial cancer in women with endometrial biopsy (n=397) showed a distinct survival curve of AGC-EC from AGC-NOS and AGC-EM (p=0.014, Fig.1). Furthermore, Log Rank test which analyzed time-to-all invasive cancers in women with at least one follow up visit post-AGC (n=641) showed a distinct survival curve of AGC-EC from AGC-NOS and AGC-EM (p=0.012, Fig.2).
Conclusions: The incidence of AGC (0.2%) in our institution was similar to the incidence in previous reports. Each of the AGC subclasses carries a different risk for post-AGC endometrial cancers and all cancers. The risk profile of AGC-EC for developing and time-to-developing, post-AGC cancers is distinctly less severe than AGC-NOS and AGC-EM. The three AGC subclasses may carry different risk profiles for developing, and time to develop, post-AGC invasive cancers, including but not limited to endometrial cancer. There may be a stepwise increase in the risk of post-AGC malignancies across AGC subclasses from AGC-EC to AGC-NOS to AGC-EM. The risk profiles of AGC-NOS should not be underrated, thus AGC-NOS may warrant the similar initial workup as AGC-EM. Further large population based prospective studies are needed to confirm the study findings.