Uterus

Nontumor

Histology of specimens from gender affirming surgery in individuals assigned female at birth


Editorial Board Member: Stephanie L. Skala, M.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Sandhyarani Dasaraju, M.D.
Mahmoud A. Khalifa, M.D., Ph.D.

Last staff update: 30 November 2022 (update in progress)

Copyright: 2020-2022, PathologyOutlines.com, Inc.

PubMed search: Female to male transgender histology

Sandhyarani Dasaraju, M.D.
Mahmoud A. Khalifa, M.D., Ph.D.
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Cite 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
ICD coding
  • ICD-10:
    • Z87.890 - personal history of sex reassignment
    • N85.9 - noninflammatory disorder of uterus, unspecified
    • N83.0 - follicular cyst of ovary
    • N89.9 - noninflammatory disorder of vagina, unspecified
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
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
  • Prostatic markers NKX3.1, PSA and P501S show positive staining in areas of prostatic metaplasia
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?

  1. Lack of epithelial maturation is consistent with high grade squamous intraepithelial lesion
  2. Occasional nuclear grooves and the presence of umbrella-like cells are interpreted as transitional cell metaplasia
  3. p16 immunohistochemistry will not be of value in this case since it is not reliable in cases of low grade squamous intraepithelial lesions
  4. Plump nuclei and prominent nucleoli suggest reactive inflammatory atypia and regeneration
  5. 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

Comment Here

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?

  1. Atypical endometrial hyperplasia
  2. Endocervical polyp
  3. Follicular cysts of the ovary
  4. Leiomyomata
  5. Serous carcinoma of the uterus
Board review style answer #2
Board review style question #3
What is the common epithelial change seen in gender affirming vaginectomy specimens?

  1. Endometriosis
  2. Mucinous metaplasia
  3. Prostatic metaplasia
  4. Tubal metaplasia
  5. Vaginal adenosis
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