Updated: Aug 15, 2018
  • Author: Wellman W Cheung, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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Practice Essentials

Trigonitis refers to the nonkeratinizing squamous metaplastic changes in the bladder trigone. The trigone is the triangular area of the bladder bound by the ureteral orifices and the internal urethral sphincter, which is normally lined by urothelium, a type of transitional epithelial tissue. [1]  This entity was first described by Heymann in 1905 as cystitis trigoni [2]  and was subsequently described by Cifuentes as a true trigonal membrane. [3]  It is also referred to in the literature as pseudomembranous trigonitis or vaginal metaplasia.

Squamous metaplasia of the trigone occurs almost exclusively in women of childbearing age. It is almost nonexistent in children. Although the exact cause of trigonitis is unknown, the condition usually occurs in response to an irritative (eg, chronic indwelling catheter) or infectious process.

Trigonitis is a benign lesion without malignant potential. It does not require follow-up cystoscopy. However, it should be distinguished from keratinizing squamous metaplasia (leukoplakia), which does require follow-up.

For patient education resources, visit Cancer Center. Also, see Cystoscopy (which is necessary to diagnose trigonitis) and Bladder Cancer.



Trigonitis, despite its name suggestive of inflammation, is a metaplastic process. Although the precise underlying cause is not known, squamous metaplasia in the bladder usually occurs in response to an irritative (eg, chronic indwelling catheter) or infectious process.

Because nonkeratinizing squamous metaplasia is most commonly found in adult women of childbearing age, a hormonal influence is posited. In a study of bladder biopsies performed in women with pseudomembranous trigonitis and women who underwent cystoscopy for staging gynecological cancer, estrogen and progesterone receptors were found in the trigone in association with squamous metaplastic changes. [4] In a more extensive mapping of estrogen and progesterone receptors in the female lower urinary tract, both were found in squamous epithelial tissue, including the transitional cell epithelium in the trigone and proximal urethra that has undergone squamous metaplastic change. [5]

In the first known case report of a 16-year-old boy with Klinefelter syndrome diagnosed with pseudomembranous trigonitis, the findings of raised estrogen levels in conjunction with increased expression of estrogen receptors in the trigone area of the biopsy suggest that estrogen could be an etiological driver, much like the association of Klinefelter syndrome with estrogen-driven cancers such as breast cancer. [6]

However, whether hormonal influences lead to squamous metaplasia is unclear. Others have suggested that squamous cell metaplasia is not associated with increased estrogen activity. [7, 8] Kvist et al did not find estrogen receptors in 36 historically collected samples of squamous metaplasia of the bladder urothelium, although the authors posited that relatively few existing receptors might have been destroyed in the tissue preparation process. [8]

Instead, other explanations focus on the potential role of chronic inflammation and/or a deficient urothelium. In one autopsy study of adult women, histological evidence of chronic inflammation was found significantly more often in bladders with squamous metaplasia. The authors suggest that squamous metaplasia is not a consequence of chronic inflammation but rather that its surface characteristics may predispose to chronic infection. [9]

Squamous metaplasia is observed over edematous or inflamed lamina propria. [10] Electron microscopy of the keratinizing variant has demonstrated that squamous metaplastic cells lack the tight junctions seen in normal transitional epithelial cells, which might allow urine to permeate the subepithelial layers and result in ongoing inflammation. [11]

Bacterial cystitis has been associated with the development of trigonitis in cases of recurrent urinary tract infections. The interstitial cystitis literature suggests that the mucosal coating of the bladder surface, also known as the glycosaminoglycan (GAG) layer, plays an important role in preventing the permeability of urinary solutes into the bladder wall. [12]   Restriction of the characteristic lesion to the trigone of the bladder is possibly due to the estrogenic effect. This could be explained by the fact that the trigone is anatomically and embryologically distinct from the remainder of the bladder, thereby allowing the trigonal epithelium to respond to estrogenic stimulation. [13]  

Defects in this protective mechanism, or injuries resulting from chronic irritation or recurrent infections, may result in chronic inflammatory changes leading to metaplasia. However, not all individuals with squamous metaplasia are symptomatic, and not all symptomatic patients have squamous metaplasia.



The frequency of trigonitis differs according to various reports. Nonkeratinizing squamous metaplasia of the bladder neck and trigone can be seen in 50-70% of premenopausal women and is considered a normal variant. [7, 11] When Wiener et al examined 100 grossly normal bladders at autopsy, they found squamous metaplasia in 46% of premenopausal and postmenopausal women and 7% of men. [14] Another autopsy study of 106 women who died from nongenitourinary causes found that 72% exhibited squamous metaplasia in the trigone. [9] Other reports suggest that trigonitis occurs in approximately 40% of adult women and approximately 5% of men. [15] It may also be seen in men receiving hormonal therapy for prostate cancer. [16]  

Squamous metaplasia of the trigone occurs almost exclusively in women of childbearing age. It is almost nonexistent in children.



The prognosis for patients with nonkeratinizing squamous metaplasia of the bladder is excellent. 

Trigonitis, or nonkeratinizing squamous metaplasia, is considered benign and without malignant potential. However, it must be differentiated from keratinizing squamous metaplasia, also known as leukoplakia, which is characterized by downward growth of rete pegs (acanthosis), cellular atypia, and dysplasia. Leukoplakia is believed to be a response of the normal urothelium to noxious stimuli and is generally considered a premalignant lesion that may progress to squamous cell carcinoma in as many as 20% of cases. [1]  See the image below.

Keratinizing squamous metaplasia of the bladder. Keratinizing squamous metaplasia of the bladder.