Uterus
Nontumor
Female to male transgender histology
Author: Mahmoud A. Khalifa, M.D., Ph.D.
Editorial Board Member: Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 20 February 2020
Minor changes: 15 March 2020
Copyright: 2020, PathologyOutlines.com, Inc.
PubMed search: Female to male transgender [title]
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagnosis | Case reports | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Negative stains | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Khalifa MA. Female to male transgender histology. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusfmtransgenderhistologic.html. Accessed January 22nd, 2021.
Definition / general
- Hysterectomy is part of the sex reassignment surgery in female to male transgender individuals
- Surgery is typically performed following long periods of preoperative androgen administration
Essential features
- Endometrial atrophy with reduced gland to stroma ratio and occasional decidua-like change (Reprod Sci 2014;21:372, Hum Reprod 1992;7:1461, Int J Gynecol Pathol 2019;38:520)
- Ectocervical epithelial atrophy, often with transitional cell metaplasia (Int J Gynecol Pathol 1997;16:89, Int J Gynecol Pathol 2019;38:520, Int J Gynecol Pathol 2017;36:328)
- Ovaries often show large cystic follicles lined by nonluteinized granulosa cells (Int J Gynecol Pathol 2019;38:520)
- Follicular densities (primordial, intermediate and primary follicular count / square millimeter) are higher than expected for the given age (Hormones (Athens) 2015;14:190, Int J Gynecol Pathol 2019;38:520)
ICD coding
Epidemiology
- Any age, typically 20 - 45
Sites
- Uterus, cervix, ovary
Pathophysiology
- Long term androgenic medication administration
- Androgen receptor (AR) is present in endometrial cells and, when activated, regulates genes involved in cytoskeletal organization and cell progression (Reprod Sci 2014;21:372)
- Ectocervical transitional cell metaplasia has been described in postmenopausal uteri (Int J Gynecol Pathol 1997;16:89)
- Abnormally high androgen levels have been known to suppress normal follicular development (Hormones (Athens) 2015;14:190)
Etiology
- Histopathologic alterations seen in female to male transgender uteri are attributed to long term preoperative androgenic medication administration
Diagnosis
- Diagnosis is typically evident based on the information received from gynecologist (e.g. gender dysphoria)
Case reports
- 3 cases; testosterone induced "virilization" of mesonephric duct remnants and cervical squamous epithelium (Int J Gynecol Pathol 2017;36:328)
- 12 cases; 20 - 32 years old with uterine and ovarian changes (Taiwan J Obstet Gynecol 2016;55:686)
- 27 cases; 20 - 46 years old with histologic changes in hysterectomy specimens (Int J Gynecol Pathol 2019;38:520)
Gross description
- Typically unremarkable
Microscopic (histologic) description
- Endometrium:
- Inactive to atrophic endometrium
- Expanded stroma with decidua-like changes with / without glandular paucity (Reprod Sci 2014;21:372, Hum Reprod 1992;7:1461, Int J Gynecol Pathol 2019;38:520)
- Cervix:
- Ectocervical epithelial atrophy, often with transitional cell metaplasia
- Umbrella-like cells may be seen on the surface
- Nuclei often show nuclear grooves
- Koilocytotic atypia (with perinuclear halos) and viral cytopathic changes are distinctly absent (Int J Gynecol Pathol 1997;16:89, Int J Gynecol Pathol 2019;38:520)
- Rarely, prostate type glands involving the ectocervical epithelium and the transformation zone (Int J Gynecol Pathol 2017;36:328)
- Ovary:
- Large cortical cystic follicles lined by nonluteinized granulosa cells (Int J Gynecol Pathol 2019;38:520)
- Follicular density (primordial, intermediate and primary follicular count / square millimeter) higher than expected for the given age (Hormones (Athens) 2015;14:190, Int J Gynecol Pathol 2019;38:520)
- Fallopian tube:
- Rarely, virilized mesonephric duct remnants (Int J Gynecol Pathol 2017;36:328)
Microscopic (histologic) images
Contributed by Mahmoud A. Khalifa, M.D., Ph.D.
Plump stromal cells and gland paucity
Ectocervical transitional cell metaplasia
High follicular density and cystic follicles
Negative stains
- p16 in cervix
Sample pathology report
- Uterus, fallopian tubes and ovaries, hysterectomy with bilateral salpingo-oophorectomy:
- Inactive / atrophic endometrium with areas of decidua-like change and gland paucity
- Myometrium with no significant histologic abnormality
- Cervix with transitional cell metaplasia of ectocervix
- Ovaries with cystic follicles and follicular density higher than expected for the patient's age
Differential diagnosis
- High grade squamous intraepithelial lesion (HSIL)
- Loss of polarity, cytologic atypia and mitotic figures
- Immature cells with high N/C ratio, irregular nuclear contour and coarse chromatin
- Superficial cells may show koilocytotic atypia and viral cytopathic changes
- p16 shows strong and diffuse nuclear staining
Board review style question #1
- In a hysterectomy from a 27 year old individual with gender dysphoria, the cervical section exhibited the area depicted in the photomicrograph shown above. Which of the following is true?
- Lack of epithelial maturation is consistent with a high grade squamous intraepithelial lesion
- Occasional nuclear grooves and the presence of umbrella-like cells are interpreted as transitional cell metaplasia
- Occasional perinuclear halos consistent with human papillomavirus infection
- p16 immunohistochemistry will not be of value since it is not reliable in low grade squamous intraepithelial lesions
- Plump nuclei and prominent nucleoli suggest reactive inflammatory atypia and regeneration
Board review style answer #1
B. Occasional nuclear grooves and the presence of umbrella-like cells are interpreted as transitional cell metaplasia
Reference: Female to male transgender histologic features
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Reference: Female to male transgender histologic features
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Board review style question #2
- Which of the following is a known outcome of long term administration of androgen to a young individual with female phenotype?
- Serous carcinoma of the uterus
- Leiomyomata
- Atypical endometrial hyperplasia
- Endocervical polyp
- Cystic follicles of the ovary
Board review style answer #2
E. Cystic follicles of the ovary
Reference: Female to male transgender histologic features
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Reference: Female to male transgender histologic features
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