WHO / ISUP classification
Carcinoma in situ

Author: Sean Williamson, M.D. (see Authors page)

Revised: 11 September 2017, last major update June 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Ureters carcinoma in situ [title]

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Cite this page: Williamson, S. Carcinoma in situ. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/ureterscis.html. Accessed September 17th, 2019.
Definition / general
  • Also called high grade intraurothelial neoplasia (HG IUN); severe dysplasia
  • By definition a flat lesion without true papillary architecture
  • Often seen in conjunction with invasive carcinoma
  • May shed atypical cells into urine making cytology valuable for diagnosis (although false positives may occur with bladder contamination)
  • Primary upper urinary tract involvement is rare in comparison to urinary bladder CIS
  • Bladder CIS is a risk factor for recurrence in the upper urinary tract in some settings; however, utility of frozen section evaluation of ureter margin is unclear (presence of “skip” lesions and limited implications on survival and local morbidity, Cancer 2006;107:2167, J Urol 1997;158:768)
Microscopic (histologic) description
  • Flat lesion composed of increased, normal or decreased number of cell layers
  • Cytologic features include nuclear enlargement, irregular nuclear contours, hyperchromasia, mitotic figures
  • Atypia may not be full thickness (see Patterns below)
  • In bladder, nuclear area 5x lymphocytes vs. 2x lymphocytes for normal urothelium (Hum Pathol 2001;32:997)
  • Also (but less important): loss of polarity, nuclear crowding, irregular thickness of urothelium
  • Note: high grade noninvasive papillary lesions (pTa) are NOT referred to as carcinoma in situ (pTis) to avoid confusion
Microscopic (histologic) images

Images hosted on other servers:


Black arrow - normal urothelium; red arrow - CIS

Black arrow - denuded urothelium adjacent to CIS

  • Large cell CIS characterized by abundant cytoplasm
  • Small cell CIS (scant cytoplasm and sometimes prominent nucleoli; does not connote neuroendocrine differentiation)
  • Clinging CIS (or "denuding cystitis" in the bladder; rare attached atypical cells in background of denuded urothelium)
  • Cancerization of urothelium (pagetoid, undermining or overriding growth; may have preservation of umbrella cell layer)
  • Pattern need not be included in surgical pathology report
  • Associated microinvasion (2 mm or less) demonstrates invasive cells with retraction artifact mimicking vascular invasion (77% of cases of microinvasion)
  • Also nests or irregular cords, rarely as isolated single cells with or without desmoplasia (Am J Surg Pathol 2001;25:356)
Positive stains
Differential diagnosis
  • Denuded urothelium:
    • Extensively denuded epithelium is often seen in CIS ("clinging CIS" or "denuding cystitis")
    • However residual malignant cells required for diagnosis
    • Deeper sectioning of tissue block or examination of von Brunn nests may be helpful if epithelium is denuded
  • Reactive atypia:
    • Patchy CK20 in umbrella cells only
    • p53 weak / negative
    • CD44 diffusely or focally positive vs. CIS with intense CK20 and p53 positivity in 81% and 57% of cases; CD44 negative in all cases (Am J Surg Pathol 2001;25:1074)
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