Bladder
Cytology
Paris system

Author: Vaishali Pansare, M.D. (see Authors page)

Revised: 7 June 2018, last major update June 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Paris system [title]

Cite this page: Pansare, V. Paris system. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bladdercytologyparissystem.html. Accessed July 20th, 2018.
Definition / general
  • Paris System for reporting urinary cytology: based on the principle that the ultimate goal of urine cytology is detection of high grade urothelial carcinoma
Specimen adequacy
  • Adequacy refers to the usefulness of the specimen to diagnose or raise suspicion of urothelial carcinoma
  • Adequacy is determined by the interplay of four specimen characteristics: collection type, cellularity, volume and cytomorphologic findings
  • Of these, the cytomorphologic findings must be considered first because any atypical, suspicious or malignant cells make the specimen intrinsically adequate regardless of the volume, cellularity or collection type
  • Paris System recommends proper relationship between specimen source, cytological diagnosis, urine volume, urothelial cellularity and obscuring features, but similar to pap smear adequacy, any atypical, suspicious or malignant cells on cytology automatically becomes an adequate specimen
  • Adequate number of benign urothelial cells also supercedes any volume requirements for adequacy
  • Volume is only considered for voided specimens; low volume samples are less likely to have adequate urothelial cells, but an optimal volume has not been established
  • The Paris system indicates that for SurePath®, 30 ml is an optimal volume for voided urines but specimens should not be rejected based on low volume
  • Benign urothelial cellularity cut offs should be validated for instrumented and voided urines

    Algorithm for urine cytology adequacy

  • Negative for High Grade Urothelial Carcinoma (NHGUC)
    • To minimize lumping everything into the "atypical" category, the terminology Negative for High Grade Urothelial Carcinoma includes all entities that pose no significant risk to the patient for developing HGUC based upon available studies
    • This term also clarifies the goal of the Paris System; to highlight those cases at risk for HGUC
    • For example, radiation associated atypia is classified as Negative for High Grade Urothelial Carcinoma and not atypical
    • A urine sample (voided or instrumented) is considered Negative for High Grade Urothelial Carcinoma if any of the following components are present:
      • Benign urothelial, squamous and glandular cells
      • Benign urothelial tissue fragments (BUTF)
      • Changes associated with stones
      • Viral cytopathic effect due to polyoma virus
      • Post therapy effect, including epithelial cells from urinary diversions
    Atypical Urothelial Cells (AUC)
    • Defined as cellular changes that fulfill the major (required) criterion and only one minor criterion
    • Note: the presence of two or more minor criterion including nuclear hyperchromasia is diagnostic of Suspicious for HGUC
    • Major criterion (required):
      • Non superficial and non degenerated urothelial cells with an increased N/C ratio (> 0.5)
    • Minor criteria (one required):
      • Nuclear hyperchromasia
      • Irregular nuclear membranes
      • Irregular, coarse and clumped chromatin
    • Normal intermediate and basal urothelial cells, typically seen in instrumented urine, have high N/C ratio and frequently occur in groups; should be regarded as NHGUC
    • Diagnosis of AUC is appropriate when cells are more abnormal than NHGUC
    • AUC is appropriate when there is suspicion of HGUC but also extensive degeneration
    Suspicious for High Grade Urothelial Carcinoma (SHGUC)
    • Reflects the presence of urothelial cells with severe atypia that falls short for a diagnosis of high grade urothelial carcinoma but beyond atypical urothelial cells
    • A diagnosis of SHGUC is defined as non superficial and non degenerated urothelial cells showing:
      • Increased N/C ratio, at least 0.5 - 0.7 (required criterion)
      • Moderate to severe nuclear hyperchromasia (required criterion) and at least one of the following:
        • Irregular clumpy chromatin
        • Marked irregular nuclear membranes
    High Grade Urothelial Carcinoma (HGUC)
    • Sensitivity of urine cytology for HGUC is 50 - 85%
    • Positive urine cytology is clinically meaningful
    • It is significantly associated with incidence of tumor recurrence and is independent of other clinicopathologic variables
      • Hence, positive urine cytology in primary upper urinary tract urothelial carcinoma is valuable to predict prognosis and preoperative positive urine cytology may be associated with higher prevalence of tumor recurrence
    • It can be useful to predict tumor progression

      Notes:
    • Urine cytology cannot distinguish invasive HGUC and carcinoma in situ (CIS)
    • Squamous or glandular differentiation of urothelial carcinoma may be seen in urine cytology but a diagnosis of squamous cell carcinoma or adenocarcinoma of the urinary tract can only be made after examination of biopsy or cystectomy specimens
    • HGUC is diagnosed on the basis of this criteria according to the Paris System consensus:
      • Cellularity; at least 5 - 10 abnormal cells
      • N/C ratio: 0.7 or greater
      • Nucleus: moderate to severe hyperchromasia
      • Nuclear membrane: markedly irregular
      • Chromatin: coarse / clumped
    • Other notable cytomorphologic features of HGUC are:
      • Cellular pleomorphism
      • Marked variation in cellular size and shapes. i.e. oval, rounded, elongated or plasmacytoid (comet cells)
      • Scant, pale or dense cytoplasm
      • Prominent nucleoli
      • Mitoses
      • Necrotic debris
      • Inflammation
    Low Grade Urothelial Neoplasia (LGUN)
    • LGUN is a combined cytologic term for low grade papillary urothelial neoplasms, which includes urothelial papilloma, papillary urothelial neoplasm of uncertain malignant potential (PUNLMP) and low grade papillary urothelial carcinoma (LGPUC)
    • Cytologic criteria of LGUN (regardless of voided urine or instrumented urine):
      • Three dimensional cellular papillary clusters with fibrovascular cores including capillaries
      • Cellular papillary clusters are defined as clusters of cells with nuclear overlapping forming "papillae"
      • Definitive diagnosis of LGUN is possible only in the presence of this feature
    • These cases should be categorized as NHGUC:
      • Three dimensional cellular clusters without fibrovascular cores
      • Increased numbers of single monotonous (non umbrella) cells
    • Rate of recurrence is 8% for papillomas, 35 - 47% for PUNLMP and 48 - 71% for LGPUC
    • Rate of progression is 0% for papillomas, 3.6% for PUNLMP and 5 - 25% for LGPUC (WHO / ISUP classification (2004))
    Squamous Cell Carcinoma (SCC)
    • Accounts for 2 - 5% of all bladder cancer in West
    • In North Africa and Middle East where Schistosoma hematobium infestation is endemic, it accounts for 25 - 30% of bladder malignancies
    • Cases not associated with Schsitosoma (non bilharzial) are usually associated with conditions causing urinary stasis with epithelial injury, such as spinal cord injury or paraplegia
    • Cytologic features of bladder SCC are similar to SCC elsewhere
    • Diagnostic criteria for SCC:
      • Cellular specimen with numerous individual and nests of squamous cells
      • Tumor cells are large, polygonal with keratinized cytoplasm, sharp borders and mildly to markedly atypical hyperchromatic nuclei
      • Fiber and tadpole cells, squamous pearls and "cell in cell" arrangement may be present
      • Background may show fragments of anucleated squamous cells, small atypical parakeratotic cells, necrosis, RBCs and neutrophils
      • Nonkeratinizing malignant cell groups with metaplastic appearance may be present
      • Liquid based preparations show similar morphology but the background is cleaner so cell details are better preserved
    Adenocarcinoma
    • Accounts for 0.5 - 2.5% of all primary bladder malignancies and includes vesical and urachal subtypes
    • Urachal adenocarcinoma develops within urachal remnants located in bladder dome
    • Primary urinary tract adenocarcinoma is less common than secondary involvement from adjacent organs
    • Risk factors include cystitis glandularis of intestinal type and bladder exstrophy
    • Diagnostic criteria:
      • Variable cellularity
      • Enteric / colonic type columnar cell clusters and single degenerated cells in a background of necrosis and mucin
      • Nuclei are large vesicular or hyperchromatic, with irregular shapes and prominent nucleoli
      • Cytoplasm may be vacuolated
    • Mucinous / colloid type has rounded 3-D clusters of crowded, bland cells with small to moderate amounts of lacy cytoplasm with occasional mucin vacuoles and medium sized nuclei with visible nucleoli in mucinous background
    • Signet ring cell carcinoma: cells with large cytoplasmic mucin filled vacuole that appear optically clear or finely vacuolated, pushing the nucleus to the periphery
    • Clear cell adenocarcinoma: cells with abundant vacuolated cytoplasm and centrally located nuclei that may be present in clusters with hobnail configuration
    Small cell carcinoma
    • Accounts for less than 1% of all bladder malignancies
    • Diagnostic criteria:
      • Moderate to high cellularity
      • Hemorrhagic and necrotic background with apoptosis, isolated or small groups of small, undifferentiated malignant cells, mitoses and numerous neutrophils
      • Cells are arranged singly, in linear pattern with rosettes, loosely or tightly cohesive clusters
      • Tumor cells are round to oval or irregular and small to medium in size (2 - 3 x lymphocytes)
      • Nuclei are small to oval, hyperchromatic with finely granular evenly distributed or smudged chromatin, ill defined membranes, prominent molding and display crush artifact
      • Nucleoli are inconspicuous
      • Scanty cytoplasm
      • High N:C ratio