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Definition / general | Microscopic (histologic) description | Microscopic (histologic) images | Additional referencesCite this page: Progestin therapy related changes. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusprogestinrelated.html. Accessed July 16th, 2017.
Definition / general
- Hysterectomy is the standard treatment for endometrioid intraepithelial neoplasia / atypical hyperplasia and endometrial endometrioid adenocarcinoma
- However, the proportion of premenopausal women with these diagnoses is increasing: 15 - 25% are premenopausal (Int J Womens Health 2014;6:691), 10% are < 45 years, 4% are < 40 years
- Hormonal therapy is now a valid alternative for pre-menopausal women who desire to preserve fertility
- Two types of fertility sparing treatment are oral progestins and Levonorgestrel releasing intrauterine device
- Indications for fertility sparing treatment:
- Young woman
- High desire to retain reproductive capabilities
- Diagnosis of EIN / atypical hyperplasia or FIGO grade 1 endometrial endometrioid adenocarcinoma
- No myometrial invasion on imaging (MRI)
- The following patients are generally not eligible for fertility sparing treatment, but can be considered on a case to case basis: patients with obesity, anovulation, grade 1 endometrioid carcinoma and superficial myoinvasion on imaging, non myoinvasive grade 2 endometrioid carcinoma
- Limitations:
- 10 - 30% of patients present at advanced stage (FIGO stage III-IV), usually with ovarian / adnexal metastases, which may be only detected on hysterectomy / BSO but not with progestin treatment
- Moreover, 5 - 29% of premenopausal women have a synchronous ovarian carcinoma, which may be only detected on hysterectomy / BSO but not with progestin treatment (Int J Womens Health 2014;6:691, Obstet Gynecol 2005;106:693)
- Outcomes:
- Regression / complete response: 74.6 - 76.2%
- Recurrence after complete response: 35.4%
- Persistence / progression: 25.4% within first 3 years, 51% after 3 years, 72% after 7 years
- Pregnancy – live birth rate: 28 - 34.8% (73% for those who actively attempted pregnancy)
Microscopic (histologic) description
- Progestin therapy related changes in the neoplastic endometrium include:
- Architectural changes
- Decreased volume of disease (% and number of involved fragments)
- Decreased glandular crowding
- Low to absent nuclear stratification
- Decreased cellularity (associated with complete response)
- Cytologic changes
- Decreased nuclear to cytoplasmic ratio
- Decreased nuclear size
- Cytoplasmic eosinophilia
- Nuclear rounding
- Metaplasia (secretory, squamous, mucinous)
- Architectural changes
- Progestin related glandular and stromal changes in the background benign endometrium:
- Their presence is an indicator of patient compliance with the treatment
- Conversely, their absence suggests lack of patient adherence (in case of oral progestins) or malfunction (in case of intrauterine device)
- Diagnosis of the degree of response to progestin therapy:
- Four categories: resolution, regression, persistence or progression
- Regression or resolution are achieved in a span of 6 months in most cases (Am J Surg Pathol 2007;31:988)
- It has been postulated that 6 months is a prudent period for conservative treatment and followup sampling
- After 6 months, the likelihood of regression or resolution is less, and definitive management (hysterectomy) is indicated
- Diagnostic workup of followup endometrial samples in patients with fertility sparing treatment:
- Document the time interval between initial diagnosis and followup
- Compare initial and followup samples (if possible)
- Determine the degree of response (see chart above)
- Determine the status of the background benign endometrium (with or without progestin therapy related changes)
| Initial (pre-treatment) diagnosis | |||
| Atypical hyerplasia / EIN | FIGO 1 endometrioid adenocarcinoma | ||
| Followup (post-treatment) interpretation | Resolution | Negative for residual hyperplasia or carcinoma | Negative for residual hyperplasia or carcinoma |
| Regression | Endometrial hyperplasia with progestin treatment effect | Endometrial hyperplasia with progestin treatment effect | |
| Atypical endometrial hyperplasia with no Progestin treatment effect | |||
| Persistence | Atypical endometrial hyperplasia with no progestin treatment effect | FIGO 1 endometrioid adenocarcinoma with no progestin treatment effect | |
| FIGO 1 endometrioid adenocarcinoma with progestin treatment effect | |||
| Progression | Endometrial endometrioid adenocarcinoma | FIGO 2 or 3 endometrioid adenocarcinoma | |
Microscopic (histologic) images
Images hosted on PathOut servers:
Progestin treated EIN, courtesy of Dr. Carlos Parra-Herran
Additional references
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