Assessing Endometrial Hyperplasia and Carcinoma Treated with Progestin Therapy
Mark J Mentrikoski, Akeesha A Shah, Krisztina Hanley, Kristen Atkins. University of Virginia, Charlottesville, VA; Emory University, Atlanta, GA
Background: Progesterone treatment is an alternative to hysterectomy in some patients with complex atypical hyperplasia (CAH) and well differentiated endometrial carcinoma (WDC). In 2007, Wheeler et al. proposed a classification scheme for assessment of treated CAH and WDC. They concluded that after 6 months of treatment persistent cytologic atypia and architectural abnormalities were associated with treatment failure. This study aims to assess the criteria proposed by Wheeler et al.
Design: With IRB approval, 30 cases of progesterone treated CAH (18) and WDC (12) were assessed. Patients were 18 to 78 years old (mean 49) and 16 were premenopausal. The initial endometrial biopsy, treatment biopsies/currettages, and hysterectomy specimens (when available) were classified by the WHO criteria for CAH and WDC. Applying the features used by Wheeler et. al, progesterone- related changes were assessed at 3-6 month intervals for the following features: gland:stroma, architectural abnormalities, mitotic activity, nucleus: cytoplasm, presence of nucleoli, nuclear chromatin quality, cytoplasmic metaplasia, and cytologic atypia (defined as coarse chromatin, prominent nucleoli, and irregular nuclear contours). Architectural abnormalities included increased gland:stroma ratio and gland confluency (cribriforming/papillary). Outcomes were defined by diagnosis of the last available specimen as resolution (benign/inactive endometrium), regression (hyperplasia without atypia), persistence (CAH or WDC), or progression (CAH to WDC/WDC to poorly-differentiated carcinoma).
Results: Outcomes were: resolution (21 cases), regression (2 cases), persistence (3 cases), and progression (4 cases). Frequently early biopsies showed increased glandular crowding and cytoplasmic metaplasias (eosinophilic, secretory, and squamous) but this did not predict poor outcome. Resolution was most predictably detected by the complete absence of cytologic atypia in the six month post-treatment specimens. All cases with persistence or progression retained cytologic atypia for at least six months.
Conclusions: Our study confirms the results of Wheeler et al. Persistence of cytologic atypia after six months of therapy is a strong indicator of treatment failure.
Since cytologic atypia is subjective, comparison to the patient's previous pre- and post-treatment biopsies is essential for proper assessment.
Increased architectural complexity is common in early progesterone treatment and should not count as progression of disease.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 174, Monday Morning