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Micropapillary Urothelial (Transitional Cell) Carcinoma

Definition

  • Aggressive subtype of urothelial neoplasm that invades as small clusters of cells

Note

Diagnostic Criteria

  • Any component of micropapillary pattern should be reflected in the diagnosis
    • Even small foci are associated with poor prognosis
  • Primarily defined by pattern of invasion
    • Invasion by small clusters of cells
      • Mean width of clusters <4.5 cells across
      • Nuclei predominantly peripheral
        • Produces rosette like appearance
      • Prominent retraction produces spaces around clusters
        • Simulates lymphatic involvement, whis is frequently present too
        • Frequently multiple clusters in the same retraction space
      • Focal intracytoplasmic mucin may be present
    • Agressive, permeative invasion is characteristic
      • Cancer appears to melt through the muscularis propria
        • Frequently little or no stromal response
      • Muscularis propria involvement is generally assumed to be present even if not demonstrable in the specimens received
        • In such cases, the report should comment on the poor prognosis and high probability of undetected spread
  • Cytoplasmic vacuoles common
    • Large vacuole with surrounding cells may produce ring forms
  • Overlying surface may show usual urothelial carcinoma in situ, papillary carcinoma or micropapillary carcinoma
  • Metastases retain the micropapillary pattern

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

  • D240 stain can distinguish retraction from lymphatic invasion but ii not really necessary for clinical decisions

Differential Diagnosis

Micropapillary Variant, Urothelial Carcinoma Invasive Urothelial Carcinoma with Prominent Retraction Artifact
Predominantly small nests Larger, confluent nests
Multiple nests per space Usually one nest per space
Spaces generally do not conform to shape of nests Spaces generally follow conture of nests

Grading / Staging

Grading

  • Micropapillary carcinoma is definitionally high grade

Staging

  • Usual rules apply, but the report should make clear the poor prognosis even if muscularis propria involvement cannot be demonstrated
  • Although non-invasive papillary urothelial neoplasms are technically in situ, they are staged as Ta and are not referred to as carcinoma in situ
  • 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
    • Pseudovascular tissue retraction is common

Clinical

  • Extremely aggressive variant of urothelial carcinoma
  • Lamina propria invasion is generally considered justification for aggressive therapy including cystectomy

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.
  • Lopez-Beltran A, Montironi R, Blanca A, Cheng L. Invasive micropapillary urothelial carcinoma of the bladder. Hum Pathol. 2010 Aug;41(8):1159-64.
  • Sangoi AR, Higgins JP, Rouse RV, Schneider AG, McKenney JK. Immunohistochemical comparison of MUC1, CA125, and Her2Neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact. Mod Pathol. 2009 May;22(5):660-7.
  • Sangoi AR, Beck AH, Amin MB, Cheng L, Epstein JI, Hansel DE, Iczkowski KA, Lopez-Beltran A, Oliva E, Paner GP, Reuter VE, Ro JY, Shah RB, Shen SS, Tamboli P, McKenney JK. Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists. Am J Surg Pathol. 2010 Sep;34(9):1367-76.
  • Shah RB, Montgomery JS, Montie JE, Kunju LP. Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: Impact of mandatory central pathology review at a large referral hospital. Urol Oncol. 2012 May 17. [Epub ahead of print]
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