Difference between revisions of "Urothelium"

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*No mitotic activity.
*No mitotic activity.


DDx:
DDx:<ref>URL: [http://pathology.jhu.edu/bladder/definitions.cfm http://pathology.jhu.edu/bladder/definitions.cfm]. Accessed on: 8 January 2014.</ref>
*[[Urothelial carcinoma in situ]].
*[[Urothelial carcinoma in situ]].
*[[Urothelial dysplasia]].
====Images====
<gallery>
Image: Benign urothelium with large superficial cells -- intermed mag.jpg | Benign large superf. cells - intermed. mag. (WC)
Image: Benign urothelium with large superficial cells -- high mag.jpg | Benign large superf. cells - high mag. (WC)
Image: Benign urothelium with large superficial cells -- very high mag.jpg | Benign large superf. cells - very high mag. (WC) 
</gallery>


===IHC===
===IHC===

Revision as of 03:21, 9 January 2014

The urothelium lines the upper portion of the genitourinary tract, i.e. ureters, urinary bladder), and a bit of the lower part.

Normal urothelium

Gross

Extent of urothelium

Urethra in males
  • Pre-prostatic urethra - transitional epithelium.
  • Prostatic urethra - transitional epithelium.
  • Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostratified columnar epithelium.
  • Spongy urethra - pseudostratified columnar epithelium (proximal) & stratified squamous (distal).

Microscopic

Features:

  • Maturation (cuboidal at base - squamoid at surface).
    • Surface cells called 'umbrella cells' (umbrella cells CK20 +ve).
  • Urothelium should be 4-5 cell layers thick.
  • +/-Prominent nucleoli.

Note:

  • Should not have a papillary architecture -- if it does it is likely cancer!
    • If it is 'papillary' -- it must have fibrovascular cores.

Sign out

URINARY BLADDER LESION, TRANSURETHRAL RESECTION:
- UROTHELIAL MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR MALIGNANCY.

Micro

The sections shows urothelium with underlying tissue. The urothelium is 4-5 cells thick. Umbrella cells are present. Few mononuclear inflammatory cells are seen in the subepithelial tissue.

The urothelium has no nuclear hyperchromasia and no significant nuclear enlargement. Mitotic activity is not identified. No papillary structures are present.

Approach

Where to start

July 1st PGY-2:

  1. Urothelial carcinoma - essentially defined by increased nuclear size +/- irreg. nuclear contour.
    • Nucleoli are common in urothelium.
      • This can be confusing... prostate carcinoma has nucleoli.
    • Mitosis - these are key if the nuclear enlargement is not present.[1]
    • Cell-depleted urothelium, where the cells have shed-off--but a few remain, should raise suspicions to cancer.
      • Thickness of the urothelium, otherwise, isn't very useful for diagnosing cancer.
  2. Round structures should make you think of papillae and prompt looking for fibrovascular cores.
  3. Fibrovascular cores = papillae... may be cancer!

A checklist-like approach

  1. Papillary structure - with fibrovascular cores?
    • Nuclear pleomorphism?
      • Yes - high grade (4-5x lymphocyte) --> Dx: high grade papillary urothelial carcinoma
      • No - low grade or normal (2-3x lymphocyte) --> DDx: low grade papillary urothelial carcinoma, PUNLMP, papilloma
  2. Flat lesions?
    • Nuclear pleomorphism?
  3. Maturation to surface?
    • No --> Dx: sectioning artefact vs. flat UCC.
    • Yes --> likely benign.
  4. Normal thickness?
    • Normal is 4-5 cell layers.
  5. Nests of glandular cells
  6. Inflammation?
    • Michaelis-Gutman bodies?

Pitfalls:

  • Urothelial carcinoma of the bladder may be confused with a paraganglioma of the bladder.
    • Way to differentiate: paraganglioma = stippled chromatin, UCC = single nucleoli.

Note about terminology

  • The bladder is rather unique in that "carcinoma" is a label used for things that are non-invasive.
    • It has been suggested that many things that are called papillary urothelial carcinoma, would be better described as papillary intraurothelial neoplasia.[2]
    • If the terminology in the urinary bladder were applied to the colon, we'd call all adenomas, i.e. pre-malignant lesions, carcinomas.

Overview in tables

General categorization

Urothelial lesions can broadly be divided into:

  1. Flat lesions.
    • Lack papillae.
    • Tend to be more aggressive.
  2. Papillary lesions.
    • Must have true papillae.
    • Very common.
    • More often benign/indolent.

Flat urothelial lesions

Comparison urothelial changes - flat epithelium - benign/premalignant/cancerous:[3]

Diagnosis Nuclear enlargement
(X stromal lymphocyte)
Nucleoli size var., shape Polarity Mitoses Thickness Inflammation Other
Normal none (2x) small none, round matures to surface none/minimal 4-5 cells none -
Reactive atypia moderate, prominent (3x) prominent none, round as normal some, none atypical as normal severe, acute or chronic -
Flat urothelial hyperplasia none (2x) small none, round as normal as normal increased usu. none -
Urothelial dysplasia moderate (3x) small, some multiple mod. variation, some irregularity lost rare, none atypical as normal usu. none -
UCC in situ signif. (4-5x) +/-large marked, irregular lost common, atypical thin, thick or norm. +/- -
Invasive UCC signif. (4-5X) +/-large marked, irregular lost common, atypical thin, thick or norm. +/- stromal invasion

The bold entry is considered the key feature.

Papillary urothelial lesions

Urothelial cells in papillae - benign/premalignant/cancerous:[4][5]

Diagnosis Papillae features Papillae branching Papillae fusion Nuclear size Mitoses DDx IHC Other Key feature
Papilloma fat papillae,
thick FV core
rare none normal (2x lymphocyte) very rare basal PUNLMP, low gr. PUCC p53-, CK20+ umbrella cells cytologically normal normal cells,
fat papillae
PUNLMP slender FV core uncommon rare enlarged - uniform rare basal only papilloma, low gr. CK20+ umbrella low cellular density (@ low power) vs. low gr.[6] uniformly enlarged cell pop.,
slender papillae
Low grade PUCC slender FV core,
thick epithelium
frequent some enlarged with variation infreq., usually basal PUNLMP, high gr. -/+ p53, CK20+ umbrella +/- small nucleoli nuc. pleomorphism,
thick epithelium
High grade PUCC mixed population common common 4-5x lymphocyte,
marked pleomorphism
common, everywhere low gr., invasive UCC diffuse CK20+, p53+ in 50% nucleoli prominent marked nuclear pleomorphism

Notes:

  • FV core = fibrovascular core.
  • PUCC = papillary urothelial carcinoma.

Risk factors for urothelial carcinoma

  • Smoking.
  • Toxins.
  • Drugs, e.g. cyclophosphamide.
  • Marijuana.[7]
  • Chinese Herbs.[8]

Others:

Flat urothelial lesions

Overview

Several different benign & pre-malignant diagnoses can be made.

The World Health Organization classification is:[10]

  • Reactive urothelial atypia.
  • Flat urothelial hyperplasia.
  • Urothelial atypia of unknown significance.
  • Urothelial dysplasia (low-grade dysplasia).
  • Urothelial carcinoma in situ (high-grade dysplasia).
  • Invasive urothelial carcinoma.

Mild urothelial atypia in normal urothelium

General

Microscopic

Features:[11]

  • Umbrella cells have:
    • Mild nuclear enlargement ~3-4x lymphocyte.
    • Round/regular nuclear membranes.
    • Focally clear cytoplasm with cobwebs.
      • Clear cytoplasm with eosinophilic reticulations.
  • +/-Inflammation.
  • No mitotic activity.

DDx:[12]

Images

IHC

  • Ki-67 low.
  • p53 -ve.

Urothelial dysplasia

  • AKA low-grade (urothelial) dysplasia.

Urothelial carcinoma in situ

  • Abbreviated CIS.
  • AKA high-grade (urothelial) dysplasia.

Urothelial cell carcinoma

See urine cytology for the cytopathology.
  • Abbreviated UCC.
  • AKA urothelial carcinoma.

Papillary urothelial lesions

Papillary urothelial lesions are grouped into one of five categories (listed from good to bad prognosis):[5]

  1. Urothelial papilloma.
  2. Inverted papilloma.
  3. Papillary urothelial neoplasm of low malignant potential (PUNLMP).
    • PUNLMP is pronouced "pun-lump".
  4. Low grade papillary urothelial carcinoma.
  5. High grade papillary urothelial carcinoma.

Key characteristics:

  1. Nuclear - size/pleomorphism.
  2. Papillae branching.
  3. Papillae fusion.

Urothelial papilloma

General

  • Very rare diagnosed.
    • If the person has a history of a low grade papillary urothelial carcinoma... it is a low grade papillary urothelial carcinoma.
    • These cases are a consensus diagnosis, i.e. you show it to a colleague... if they agree you can call it.

Microscopic

Features:[5]

  • Papillary fronds.
  • Minimal branching or fusion.
  • Cytological features of normal urothelium.
    • Normal urothelium approx. 2x the size of stromal lymphocytes.[13]
  • No mitoses.
  • Thickness < 7 cells.[citation needed]

DDx:

Inverted urothelial papilloma

General

  • May be confused with papillary urothelial carcinoma with an inverted growth pattern.

Microscopic

Features:

  • Like papillomas... but grow downward.[5]
  • According to THvdK,[14] inverted papillomas never have an exophytic component; if an exophytic component is present it is urothelial carcinoma. This is disputed by one paper from Mexico that examines two cases.[15]
  • Nests have peripheral palisading of nuclei - important.

DDx:

Images

IHC

May be useful versus inverted growth pattern UCC:[16]

  • Ki-67 -ve.
  • CK20 -ve.
  • p53 -ve (rarely +ve).

Papillary urothelial neoplasm of low malignant potential

  • Abbreviated PUNLMP.
    • This is pronounced pun-lump.

General

Treatment:

Microscopic

Features:[5]

  • Rare fused papillae.
  • Infrequent mitoses.
  • Nuclei larger than papilloma - but monotonous.[21]

DDx:

Images

Low-grade papillary urothelial carcinoma

  • Abbreviated LGPUC.[22]
  • AKA low-grade papillary urothelial cell carcinoma.

High-grade papillary urothelial carcinoma

  • Abbreviated HGPUC.
  • AKA high-grade papillary urothelial cell carcinoma, abbreviated HGPUCC.

Benign urothelial lesions

The big table of cystitis:

Type Key feature DDx Reference
Florid proliferative cystitis expanded lamina propria with von Brunn's nests, cystitis cystica et glandularis von Brunn's nests, cystitis cystica et glandularis, low-grade urothelial carcinoma [23]
Polypoid cystitis wide base, height > base papillary cystitis, bullous cystitis [24]
Bullous cystitis wide base, height < base papillary cystitis, polypoid cystitis [24]
Papillary cystitis narrow base, height > base polypoid cystitis, bullous cystitis [24]
Interstitial cystitis +/-ulceration (uncommon) - requires clinical correlation urothelial CIS [25]
Follicular cystitis lymphoid follicles non-Hodgkin lymphoma [26]
Infectious cystitis dependent cause (bacterial, viral, fungal) [27]
Granulomatous cystitis granulomas tuberculosis, schistosomiasis, fungal infection, post-BCG [27]
Radiation cystitis edema, vascular congestion, +/- erosions -- acute; fibrosis in LP and detrusor -- chronic [28]

Interstitial cystitis

General

  • Chronic cystitis, culture negative.
  • Treatment difficult.[29]

Epidemiology:[30]

  • Women > men.

Symptoms:[30]

  • Urgency.
  • Frequency.
  • Pain.

Microscopic

Features:[25]

  • +/-Ulceration (uncommon).

Note:

DDx:

  • Urothelial CIS.

Follicular cystitis

Microscopic

Features:[26]

  • Lymphoid follicles in the lamina propria.

DDx:

Sign out

URINARY BLADDER, BIOPSY:
- UROTHELIAL MUCOSA WITH CHRONIC INFLAMMATION AND BENIGN LYMPHOID NODULES WITH GERMINAL CENTRE FORMATION.
- MUSCULARIS PROPRIA PRESENT.
- NEGATIVE FOR UROTHELIAL CARCINOMA IN SITU AND NEGATIVE FOR MALIGNANCY.

Polypoid cystitis

General

  • Uncommon.
  • Wide age range.
  • Benign.

Microscopic

Features:[24]

  • Polypoid urothelium-covered projections with:
    1. Broad bases.
    2. Height > base.
    3. Extensive edema.

DDx:

  • Papillary cystitis - not a broad base.
  • Bullous cystitis.

Image:

von Brunn nests

General

  • Benign.

Microscopic

Features:[31]

  • Nests of (benign) urothelium budding into the lamina propria.

Note:

  • Nests should not extend into the muscularis propria.

DDx:

IHC

Features:[32]

  • p53 -ve.
  • MIB-1 <3%.

Cystitis cystica

General

Microscopic

Features:[31]

  • Nests of urothelium within the lamina propria with cyst formation, i.e. lumens are present.

Note:

  • Nests should not extend into the muscularis propria.

DDx:

Image:

Sign out

URINARY BLADDER, BIOPSY:
- CYSTITIS CYSTICA.
- NEGATIVE FOR MALIGNANCY.

Cystitis glandularis

Cystitis cystica et glandularis
External resources
EHVSC 10173
Cystitis cystica et glandularis redirects to here.

General

  • Benign.
  • Can be thought of as cystitis cystica with mucin-secreting cells lining the cystic spaces.[33]
  • When seen in conjunction with cystitis cystica it is called cystitis cystica et glandularis.

Note:

  • There are case reports of urethritis glandularis - the same lesion in the urethra.[36][37]

Microscopic

Features:[31]

  • Nests of urothelium within the lamina propria with cyst formation, i.e. lumens are present.
  • Cyst lining cells are cuboidal and/or columnar epithelium.
    • Produce mucin.
  • +/-Goblet cells, i.e. intestinal metaplasia.[33]

Note:

  • Nests should not extend into the muscularis propria.

Image:

Sign out

URINARY BLADDER NECK, BIOPSY:
- CYSTITIS CYSTICA ET GLANDULARIS.
- NEGATIVE FOR MALIGNANCY.

Micro

The sections show urothelial mucosa with bland nests within the lamina propria with cyst formation. The stroma is edematous and has a mixed inflammatory infiltrate consisting of plasma cells, eosinophils, lymphocytes and neutrophils.

Malakoplakia

Nephrogenic adenoma

  • AKA mesonephric adenoma.
  • AKA nephrogenic metaplasia.

See also

References

  1. JS. 9 June 2010.
  2. Van der Kwast, TH.; Zlotta, AR.; Fleshner, N.; Jewett, M.; Lopez-Beltran, A.; Montironi, R. (Dec 2008). "Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.". Anal Quant Cytol Histol 30 (6): 309-15. PMID 19160695.
  3. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 155-163. ISBN 978-0443066771.
  4. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 166-175. ISBN 978-0443066771.
  5. 5.0 5.1 5.2 5.3 5.4 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 310. ISBN 978-0781765275.
  6. GAG. 26 February 2009.
  7. Chacko, JA.; Heiner, JG.; Siu, W.; Macy, M.; Terris, MK. (Jan 2006). "Association between marijuana use and transitional cell carcinoma.". Urology 67 (1): 100-4. doi:10.1016/j.urology.2005.07.005. PMID 16413342.
  8. URL: http://content.nejm.org/cgi/content/full/343/17/1268. Accessed on: 27 May 2010.
  9. Crockett, DG.; Wagner, DG.; Holmäng, S.; Johansson, SL.; Lynch, HT. (May 2011). "Upper urinary tract carcinoma in Lynch syndrome cases.". J Urol 185 (5): 1627-30. doi:10.1016/j.juro.2010.12.102. PMID 21419447.
  10. Hodges, KB.; Lopez-Beltran, A.; Davidson, DD.; Montironi, R.; Cheng, L. (Feb 2010). "Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features.". Hum Pathol 41 (2): 155-62. doi:10.1016/j.humpath.2009.07.002. PMID 19762067.
  11. 11.0 11.1 Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-57. ISBN 978-1931884280.
  12. URL: http://pathology.jhu.edu/bladder/definitions.cfm. Accessed on: 8 January 2014.
  13. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 161. ISBN 978-0443066771.
  14. THvdK. 21 June 2010.
  15. Albores-Saavedra J, Chable-Montero F, Hernández-Rodríguez OX, Montante-Montes de Oca D, Angeles-Angeles A (June 2009). "Inverted urothelial papilloma of the urinary bladder with focal papillary pattern: a previously undescribed feature". Ann Diagn Pathol 13 (3): 158–61. doi:10.1016/j.anndiagpath.2009.02.009. PMID 19433293.
  16. Jones, TD.; Zhang, S.; Lopez-Beltran, A.; Eble, JN.; Sung, MT.; MacLennan, GT.; Montironi, R.; Tan, PH. et al. (Dec 2007). "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 31 (12): 1861-7. doi:10.1097/PAS.0b013e318060cb9d. PMID 18043040.
  17. May M, Brookman-Amissah S, Roigas J, et al. (March 2009). "Prognostic Accuracy of Individual Uropathologists in Noninvasive Urinary Bladder Carcinoma: A Multicentre Study Comparing the 1973 and 2004 World Health Organisation Classifications". Eur. Urol. 57 (5): 850. doi:10.1016/j.eururo.2009.03.052. PMID 19346063.
  18. MacLennan GT, Kirkali Z, Cheng L (April 2007). "Histologic grading of noninvasive papillary urothelial neoplasms". Eur. Urol. 51 (4): 889–97; discussion 897–8. doi:10.1016/j.eururo.2006.10.037. PMID 17095142.
  19. Jones TD, Cheng L (June 2006). "Papillary urothelial neoplasm of low malignant potential: evolving terminology and concepts". J. Urol. 175 (6): 1995–2003. doi:10.1016/S0022-5347(06)00267-9. PMID 16697785.
  20. Cheng, L.; Maclennan, GT.; Lopez-Beltran, A. (Dec 2012). "Histologic grading of urothelial carcinoma: a reappraisal.". Hum Pathol 43 (12): 2097-108. doi:10.1016/j.humpath.2012.01.008. PMID 22542126.
  21. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 170. ISBN 978-0443066771.
  22. Watts, KE.; Montironi, R.; Mazzucchelli, R.; van der Kwast, T.; Osunkoya, AO.; Stephenson, AJ.; Hansel, DE. (Aug 2012). "Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma.". Urology 80 (2): 361-6. doi:10.1016/j.urology.2012.04.010. PMID 22857755.
  23. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 113. ISBN 978-0443066771.
  24. 24.0 24.1 24.2 24.3 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 120. ISBN 978-0443066771.
  25. 25.0 25.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 124. ISBN 978-0443066771.
  26. 26.0 26.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 122. ISBN 978-0443066771.
  27. 27.0 27.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 127. ISBN 978-0443066771.
  28. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 138. ISBN 978-0443066771.
  29. 29.0 29.1 Tanaka, T.; Nitta, Y.; Morimoto, K.; Nishikawa, N.; Nishihara, C.; Tamada, S.; Kawashima, H.; Nakatani, T. (2011). "Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan.". BMC Urol 11: 11. doi:10.1186/1471-2490-11-11. PMID 21609485.
  30. 30.0 30.1 30.2 French, LM.; Bhambore, N. (May 2011). "Interstitial cystitis/painful bladder syndrome.". Am Fam Physician 83 (10): 1175-81. PMID 21568251.
  31. 31.0 31.1 31.2 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1028. ISBN 0-7216-0187-1.
  32. 32.0 32.1 Volmar, KE.; Chan, TY.; De Marzo, AM.; Epstein, JI. (Sep 2003). "Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma.". Am J Surg Pathol 27 (9): 1243-52. PMID 12960809.
  33. 33.0 33.1 33.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 304. ISBN 978-0781765275.
  34. Conces, MR.; Williamson, SR.; Montironi, R.; Lopez-Beltran, A.; Scarpelli, M.; Cheng, L. (Sep 2012). "Urethral caruncle: clinicopathologic features of 41 cases.". Hum Pathol 43 (9): 1400-4. doi:10.1016/j.humpath.2011.10.015. PMID 22397870.
  35. Wasco, MJ.; Daignault, S.; Bradley, D.; Shah, RB. (Feb 2010). "Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases.". Hum Pathol 41 (2): 163-71. doi:10.1016/j.humpath.2009.07.015. PMID 19800100.
  36. Chan, YM.; Ka-Leung Cheng, D.; Nga-Yin Cheung, A.; Yuen-Sheung Ngan, H.; Wong, LC. (Dec 2000). "Female urethral adenocarcinoma arising from urethritis glandularis.". Gynecol Oncol 79 (3): 511-4. doi:10.1006/gyno.2000.5968. PMID 11104631.
  37. Yin, G.; Liu, YQ.; Gao, P.; Wang, XH. (Aug 2007). "Male urethritis glandularis: case report.". Chin Med J (Engl) 120 (16): 1460-1. PMID 17825180.