Uterus
Nontumor
Histology of specimens from gender affirming surgery in individuals assigned female at birth
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PubMed search: Female to male transgender histology
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagnosis | Case reports | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: Dasaraju S, Khalifa MA. Histology of specimens from gender affirming surgery in individuals assigned female at birth. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusfmtransgenderhistologic.html. Accessed December 1st, 2022.
Definition / general
- Hysterectomy is part of gender affirming surgery for individuals assigned female at birth (AFAB)
- Vaginectomy is a rarely performed gender affirming surgery for individuals AFAB
- Surgery is typically performed following long periods of preoperative androgen administration
Essential features
- Cervical pathology in the form of ectocervical epithelial atrophy, often with transitional cell metaplasia, should not be mistaken for high grade dysplasia (Int J Gynecol Pathol 1997;16:89, Int J Gynecol Pathol 2019;38:520)
- Rarely, prostate type glands can be seen in the ectocervical epithelium (Histopathology 2022;80:946, Int J Gynecol Pathol 2017;36:328)
- Vaginal pathology shows epithelial atrophy, transitional cell metaplasia and prostatic metaplasia; these should not be mistaken for dysplasia or glandular proliferative abnormalities (Am J Clin Pathol 2022 Oct 7 [Epub ahead of print], Am J Surg Pathol 2020;44:1040, Arch Pathol Lab Med 2022;146:742)
- Ovaries often show large follicular cysts lined by nonluteinized granulosa cells (Int J Gynecol Pathol 2019;38:520)
- Follicular density (primordial, intermediate and primary follicular count per mm2) is 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 years old
Sites
- Uterus, cervix, vagina, 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 uteruses (Int J Gynecol Pathol 1997;16:89)
- Prostatic metaplasia and transitional cell metaplasia of the vagina is associated with long term androgen administration (Am J Surg Pathol 2020;44:1040)
- Abnormally high androgen levels are known to suppress normal follicular development (Hormones (Athens) 2015;14:190)
Etiology
- Histopathologic alterations seen in the uterus, vagina and ovary of individuals assigned female at birth 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
- 23 year old patient assigned female at birth with adrenogenital syndrome, presenting with transitional cell metaplasia and ectopic prostatic tissue in the uterine cervix and vagina (Int J Gynecol Pathol 2004;23:182)
- 3 cases of testosterone induced virilization of mesonephric duct remnants and cervical squamous epithelium in patients assigned female at birth (Int J Gynecol Pathol 2017;36:328)
- 12 patients assigned female at birth between 20 and 32 years old with uterine and ovarian changes during testosterone administration (Taiwan J Obstet Gynecol 2016;55:686)
- 13 patients assigned female at birth with prostatic metaplasia of the vagina and uterine cervix (Am J Surg Pathol 2020;44:1040)
- 27 patients assigned female at birth between 20 and 46 years old with histologic features of hysterectomy specimens (Int J Gynecol Pathol 2019;38:520)
- 55 patients assigned female at birth between 18 and 56 years old with histologic features of hysterectomy specimens (Arch Pathol Lab Med 2022;146:742)
Gross description
- Typically, gross appearance is unremarkable
Microscopic (histologic) description
- Expanded endometrial stromal areas with decidua-like changes with or without glandular paucity (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 (Arch Pathol Lab Med 2022;146:742, Surg Pathol Clin 2022;15:421, Int J Gynecol Pathol 1997;16:89, Int J Gynecol Pathol 2019;38:520)
- Umbrella-like cells could be seen on the surface
- Nuclei often show nuclear grooves
- Koilocytotic atypia (with perinuclear halos) and viral cytopathic changes are distinctly absent
- Rarely, prostate type glands can be seen in the ectocervical epithelium (Histopathology 2022;80:946, Int J Gynecol Pathol 2017;36:328)
- Vaginal epithelial atrophy, transitional cell metaplasia and prostatic metaplasia (Int J Gynecol Pathol 2004;23:182, Am J Surg Pathol 2020;44:1040)
- Large ovarian cortical follicular cysts lined by nonluteinized granulosa cells (Int J Gynecol Pathol 2019;38:520)
- Follicular density (primordial, intermediate and primary follicular count per mm2) is higher than expected for the given age (Hormones (Athens) 2015;14:190, Int J Gynecol Pathol 2019;38:520)
- Rarely, periadnexal 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
Transitional cell metaplasia of ectocervix
Follicular cysts with high follicular density
Prostatic metaplasia of vagina
NKX3.1 stain
Positive stains
Negative stains
- p16 immunostaining in the cervix is negative and is used to distinguish transitional cell metaplasia from high grade squamous intraepithelial lesion
Sample pathology report
- Uterus, fallopian tubes and ovaries, hysterectomy with bilateral salpingo-oophorectomy:
- Inactive / atrophic endometrium with areas of focal decidualization and gland paucity
- Myometrium with no significant histologic abnormality
- Cervix with transitional cell metaplasia of ectocervix
- Ovaries with follicular cysts; follicular density is higher than expected for the patient's age
- Vagina, vaginectomy:
- Vaginal tissue with epithelial atrophy with focal transitional cell metaplasia and prostate-like glands / prostatic metaplasia
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 immunohistochemical staining shows diffuse and strong nuclear and cytoplasmic staining
Additional references
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 above. Which of the following is true about this field?
- Lack of epithelial maturation is consistent with high grade squamous intraepithelial lesion
- Occasional nuclear grooves and the presence of umbrella-like cells are interpreted as transitional cell metaplasia
- p16 immunohistochemistry will not be of value in this case since it is not reliable in cases of low grade squamous intraepithelial lesions
- Plump nuclei and prominent nucleoli suggest reactive inflammatory atypia and regeneration
- The presence of occasional perinuclear halos is in keeping with human papillomavirus infection
Board review style answer #1
B. Occasional nuclear grooves and the presence of umbrella-like cells are interpreted as transitional cell metaplasia
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Reference: Histology of specimens from gender affirming surgery in individuals assigned female at birth
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Reference: Histology of specimens from gender affirming surgery in individuals assigned female at birth
Board review style question #2
Which of the following is a known outcome of long term administration of androgen to a young individual who was assigned female at birth?
- Atypical endometrial hyperplasia
- Endocervical polyp
- Follicular cysts of the ovary
- Leiomyomata
- Serous carcinoma of the uterus
Board review style answer #2
C. Follicular cysts of the ovary
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Reference: Histology of specimens from gender affirming surgery in individuals assigned female at birth
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Reference: Histology of specimens from gender affirming surgery in individuals assigned female at birth
Board review style question #3
What is the common epithelial change seen in gender affirming vaginectomy specimens?
- Endometriosis
- Mucinous metaplasia
- Prostatic metaplasia
- Tubal metaplasia
- Vaginal adenosis
Board review style answer #3
C. Prostatic metaplasia
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Reference: Histology of specimens from gender affirming surgery in individuals assigned female at birth
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Reference: Histology of specimens from gender affirming surgery in individuals assigned female at birth
