Berks County Medical Society Medical Record Fall 2017 - 24

rhs Student Sum mer Research Projects
AGC Subclasses and Risk of Invasive Cancers:
A Prospective Case Series Study
by Laura E. Smith, Xuezhi (Daniel) Jiang, MD, PhD, Peter F. Schnatz, DO
The Reading Hospital, Department of Obstetrics and Gynecology
Objectives: 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 carries
a similar risk of post-AGC invasive cancers has not been assessed1.
The objective of this study is to assess the risk of invasive cancers
associated with Atypical Glandular Cell (AGC) subclasses (EC, EM,
or NOS).
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%), AGCEM (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

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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-toendometrial 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: 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 AGCNOS should not be under-rated, 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.

Laura Smith attended Franklin & Marshall
College, and is now in her second year at the
Philadelphia College of Osteopathic Medicine.
She is VP of the PCOM chapter of the Student
Association of the American College of
Osteopathic Family Physicians.
http://berkscms.org/
Berks County Medical Society Medical Record Fall 2017

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