Microscopic Description:

Urothelium:

  • Partly ulcerated and edematous
  • Focal proliferation into subepithelial nests with central cystic change
  • Focal cytological atypia, cytoplasmic vacuoles and mitosis

Subepithelial tissue:

  • Congested and dilated vessels, extravasated RBCs, intravascular and stromal fibrin deposition, thick-walled vessels
  • Inflammatory infiltrate composed of eosinophils, neutrophils, few mast cells and lymphoplasmacytic infiltrate
  • Multinucleated stromal fibroblasts
  • Anastomosing cords and nests of urothelial cells encircling vessels
Differential diagnoses:

Careful morphological assessment and clinical correlation is mandatory for the diagnosis.

Presence of reactive atypia, edematous and ulcerated urothelium, dense inflammation, non-invasive urothelial nests with well-defined contours favor benign etiology.

In Cystitis cystica, there is marked proliferation of urothelial nests. The urothelial cells show absence of atypia, lack of dense stromal inflammation and stromal fibroblasts.

Discussion:

Well known complication of pelvic irradiation associated with high morbidity

Incidence: Variable; ranging from 9.1%-80%, mostly due to methods of evaluation, patient monitoring, underreporting of acute cases and delayed symptoms in chronic lesions(>10 years)

Pathophysiology: progressively developing endarteritis obliterans causing bladder hypoperfusion leading to necrosis of bladder mucosa and subsequently fibrosis and atrophy.

Different phases of radiation cystitis.

Radiation cystitis is debilitating complication of radiotherapy with severely impacts daily life.

Early detection mechanisms and early interventions are needed to prevent long term sequale and improved quality of life.

References:

Zwaans BM, Nicolai HG, Chancellor MB, Lamb LE. Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis. Rev Urol. 2016;18(2):57-65. doi: 10.3909/riu0700. PMID: 27601964; PMCID: PMC5010626.

Vanneste BGL, Van Limbergen EJ, Marcelissen TA, van Roermund JGH, Lutgens LC, Arnoldussen CWKP, Lambin P, Oelke M. Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis. Urol Int. 2022;106(1):63-74. doi: 10.1159/000515716. Epub 2021 Jun 15. PMID: 34130300.

Helissey C, Cavallero S, Brossard C, Dusaud M, Chargari C, François S. Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives. Cells. 2020 Dec 24;10(1):21. doi: 10.3390/cells10010021. PMID: 33374374; PMCID: PMC7823735.

Makino K, Sato Y, Takenaka R, Yamashita H, Akiyama Y, Yamada Y, Nakamura M, Kawai T, Yamada D, Suzuki M, Kume H. Cumulative Incidence and Clinical Risk Factors of Radiation Cystitis after Radiotherapy for Prostate Cancer. Urol Int. 2023;107(5):440-446. doi: 10.1159/000521723. Epub 2022 Mar 15. PMID: 35290980; PMCID: PMC10273897.

Brossard C, Lefranc AC, Simon JM, Benderitter M, Milliat F, Chapel A. Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis. Int J Mol Sci. 2022 Feb 6;23(3):1836. doi: 10.3390/ijms23031836. PMID: 35163758; PMCID: PMC8836784.

Zwaans BM, Chancellor MB, Lamb LE. Modeling and Treatment of Radiation Cystitis. Urology. 2016 Feb;88:14-21. doi: 10.1016/j.urology.2015.11.001. Epub 2015 Nov 10. PMID: 26571081.

CASE IMAGES