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Surgical Pathology Criteria
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Nested Variant Urothelial (Transitional Cell) Carcinoma

Definition

  • Urothelial carcinoma with deceptively bland appearing invasion by nests of cells

Note

Diagnostic Criteria

  • Infiltrative pattern
    • May be difficult to assess on biopsies
      • Frequently has deep foci of classical jagged invasion
    • Muscularis propria involvement is definitional if present
    • Stroma may be normal or desmoplastic
  • Predominant pattern is variably sized nests, frequently small and fused
  • Frequently forms spaces or lumens
    • Carcinoma cells forming and lining spaces lack glandular/secretory cytoplasmic differentiation
    • Lumens frequently empty, but may contain necrotic debris or PASd stainable material
    • Lining cells are transitional or squamous, PASd negative
      • No goblet cells
    • If extensive, can be termed microcystic urothelial carcinoma
  • Cytologically predominantly bland
    • Focal cytologic atypia nearly always present
      • Sometimes only in deeper tissues
  • Overlying mucosa is normal or may have papillary component
  • Frequently involves ureteral orifices
  • Aggresive, invasive carcinomas in spite of bland cytology

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 10/20/12

Supplemental studies

Immunohistology

  • Nothing useful

Differential Diagnosis

  • Inverted pattern urothelial carcinoma
  • Inverted papilloma
  • Florid von Brunn nests
  • Florid cystitis cystica/glandularis

Nested Variant Urothelial Carcinoma Transitional/Urothelial Carcinoma with Inverted Pattern
Invasive carcinoma that looks deceptively non-invasive due to predominantly nested pattern Non-invasive inverted pattern of carcinoma that looks deceptively invasive
Overall invasive pattern, not circumscribed Lacks clearly invasive pattern
May involve muscularis propria Does not involve muscularis propria
Varying sizes and shapes of nests Frequently formed by fusion of trabeculae and cords (inverted papilloma like pattern)
Desmoplastic stroma may be present No desmoplasia

Nested Variant Urothelial Carcinoma Inverted Papilloma
Overall invasive pattern, not circumscribed Circumscribed (if sample permits assessment)
May involve muscularis propria Does not involve muscularis propria
Varying sizes and shapes of nests Uniform trabeculae and cords
Disorder of cells in nests Orderly peripheral palisading and central streaming

Nested Variant Urothelial Carcinoma Florid von Brunn Nests, Cystitis Cystica/Glandularis
Infiltrative pattern Tend to have uniform depth and/or lobular architecture
Frequently invades muscularis propria Usually confined to superficial submucosa, does not involve muscularis propria
Overall cytologically bland but usually at least focally atypical Cytologically bland
Criteria above apply to both solid and cystic processes
The distinction may be very difficult on superficial biopsies
IPOX for Ki67, p53, p27 and CK20 is not helpful (Volmar)

 

Grading / Staging

Grading

  • Microcystic carcinoma is considered by some to be definitionally low grade

Staging

  • Usual rules apply
  • If possible, the extent of lamina propria / submucosa invasion should be reported
  • Muscularis mucosae is variable and its involvement does not affect staging
    • Generally loose strands of muscle
  • Muscularis propria involvement is significant and should be evaluated carefully
    • Dense, well defiined bundles of muscle
    • Depth of muscularis propria involvement cannot be assessed in transurethral specimens
    • Presence or absence of propria should be reported even if not involved
  • Lymphatic invasion should be confirmed by immunohistochemistry

Clinical

  • Same prognosis as usual invasive urothelial carcinoma
  • Should be distinguished from adenocarcinoma
    • Adenocarcinoma has worse behavior
    • Extra-urothelial primary must be ruled out for adenocarcinomas

Classification / Lists

Flat Lesions of the Urinary Bladder

Papillary Lesions of the Urinary Bladder

Subtypes of High Grade Urothelial Carcinoma

Inverted Lesions of the Urinary Bladder

Glandular Lesions of the Urinary Bladder

Bibliography

  • Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
  • Eble JN, Sauter G, Epstein JI, Sesterhenn IA eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the Urinary System and Male Genital Organs. IARC Press: Lyon 2004.
  • Cox R, Epstein JI. Large nested variant of urothelial carcinoma: 23 cases mimicking von Brunn nests and inverted growth pattern of noninvasive papillary urothelial carcinoma. Am J Surg Pathol. 2011 Sep;35(9):1337-42.
  • Dhall D, Al-Ahmadie H, Olgac S. Nested variant of urothelial carcinoma. Arch Pathol Lab Med. 2007 Nov;131(11):1725-7.
  • Hodges KB, Lopez-Beltran A, Maclennan GT, Montironi R, Cheng L. Urothelial lesions with inverted growth patterns: histogenesis, molecular genetic findings, differential diagnosis and clinical management. BJU Int. 2011 Feb;107(4):532-7
  • .Jones TD, Zhang S, Lopez-Beltran A, Eble JN, Sung MT, MacLennan GT, Montironi R, Tan PH, Zheng S, Baldridge LA, Cheng L. Urothelial carcinoma with an inverted growth pattern can be distinguished from inverted papilloma by fluorescence in situ hybridization, immunohistochemistry, and morphologic analysis. Am J Surg Pathol. 2007 Dec;31(12):1861-7.
  • Lin O, Cardillo M, Dalbagni G, Linkov I, Hutchinson B, Reuter VE. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol. 2003 Dec;16(12):1289-98
  • Wasco MJ, Daignault S, Bradley D, Shah RB. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases. Hum Pathol. 2010 Feb;41(2):163-71.
  • Leroy X, Leteurtre E, De La Taille A, Augusto D, Biserte J, Gosselin B. Microcystic transitional cell carcinoma: a report of 2 cases arising in the renal pelvis. Arch Pathol Lab Med. 2002 Jul;126(7):859-61.
  • Paz A, Rath-Wolfson L, Lask D, Koren R, Manes A, Mukamel E, Gal R. The clinical and histological features of transitional cell carcinoma of the bladder with microcysts: analysis of 12 cases. Br J Urol. 1997 May;79(5):722-5.
  • Young RH, Zukerberg LR. Microcystic transitional cell carcinomas of the urinary bladder. A report of four cases. Am J Clin Pathol. 1991 Nov;96(5):635-9.
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