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

Normal urothelium

Cystitis cystica et glandularis
	External resources
EHVSC	10173

Gross

Extent of urothelium

Ureters.
Renal pelvis.
Urinary bladder.
Part of the urethra.

Urethra in males

Pre-prostatic urethra - transitional epithelium.
Prostatic urethra - transitional epithelium.
- Cancer arising at this site is prostatic urothelial carcinoma.
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.

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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:

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.
Round structures should make you think of papillae and prompt looking for fibrovascular cores.
Fibrovascular cores = papillae... may be cancer!

A checklist-like approach

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
Flat lesions?
- Nuclear pleomorphism?
Maturation to surface?
- No --> Dx: sectioning artefact vs. flat UCC.
- Yes --> likely benign.
Normal thickness?
- Normal is 4-5 cell layers.
Nests of glandular cells
- Consider cystitis cystica, cystitis glandularis, cystitis cystica et glandularis, von Brunn's nest, inverted papilloma.
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:

Flat lesions.
- Lack papillae.
- Tend to be more aggressive.
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:

Lynch syndrome.
- Should be considered in ureteral cancers.^[9]

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

May be confused with urothelial carcinoma in situ.^[11]
Uncommon.

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:

Urothelial carcinoma in situ.

IHC

Ki-67 low.
p53 -ve.

Urothelial carcinoma in situ

Abbreviated CIS.

General

Lack papillae.

Microscopic

Features:

Nuclear changes key feature.
- Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.^[12]
  - Normal urothelium approx. 2x the size of stromal lymphocytes.
- Nuclear pleomorphism - marked variation in size of nuclei.
+/-Disordered arrangement/crowding of cells.
- In normal urothelium the cell line-up on the basement membrane.
Umbrella cells often absent.
+/-Mitoses present.
+/-Enlarged nucleoli.

Note:

The urothelium may be "depleted", i.e. exist only of rare large cells on the basement membrane.
- This is known as clinging urothelial carcinoma in situ.^[13]

IHC

Features:^[14]

p53 +ve.
Ki-67 high.

Benign urothelium vs. CIS:^[15]

CK20 +ve in deep cells (23/26 cases).
- Normal urothelium -- only the umbrella cells.
Ki-67 ~50% of cells - deep and superficial.
- Normal ~10% of cells, confined to basal aspect.

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URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): 
- UROTHELIAL CARCINOMA IN SITU.
- MUSCULARIS PROPRIA PRESENT.

Urothelial cell carcinoma

See urine cytology for the cytopathology.

Abbreviated UCC.
AKA urothelial carcinoma.

General

These lesions lack papillae and are typical flat.
Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and renal cell carcinoma.

Microscopic

Features:

Nuclear pleomorphism - key feature.
- Compare nuclei to one another.
Increased N/C ratio.
Lack of maturation to surface (important).

Cells become dyscohesive.
- Mostly useless in my experience.

Invasion vs. in situ: Useful features - present in invasion:^[16]

Thin-walled vessels.
Stromal reaction (hypercellularity).
Retraction artefact around the tumour cell nests.

Note:

The presence/absence of muscle should be commented on in biopsy specimens.
Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does not imply invasion deep to the muscularis propria.^[17]

DDx:

Pseudocarcinomatous urothelial hyperplasia.

Staging

T1 - lamina propria.
- Several subdivisions of T1 exist:
  - T1a - superficial or in muscularis mucosae.
  - T1b - beyond muscularis mucosae - into submucosa.
T2 - muscularis propria.

Subtypes of urothelial carcinoma

There are numerous subtypes:^[18]

Squamous differentiation.
Clear cell.
Plasmacytoid.
Micropapillary.
- Small nests (< ~10 cells/nest).
Sarcomatoid.
- Images: UCC with sarcomatoid differentiation (upmc.edu).
Many others...

Benign patterns - mnemonic Much GIN:

Microcystic.
Small tubular/glandular.
Inverted.
Nested.

Plasmacytoid urothelial cell carcinoma

Features:

Abundant gray cytoplasm, eccentric nucleus.

Images:

Plasmacytoid UCC - several images (upmc.edu).

Nested urothelial cell carcinoma

AKA nested variant urothelial cell carcinoma.

Features:^[19]

High density of well-circumscribed nests.
Mild-to-moderate nuclear atypia.
+/-Foci of unequivocal conventional urothelial carcinoma.
- Focally solid or gland fusion.
- Moderate-to-severe nuclear atypia +/- abundant mitoses.
+/-Extension into the muscularis propria.

DDx:

von Brunn nests.
Low grade papillary urothelial carcinoma with lamina propria invasion.

Images

Nested variant of urothelial carcinoma - intermed. mag. (WC/Nephron)
Nested variant of urothelial carcinoma - high mag. (WC/Nephron)
Nested variant of urothelial carcinoma - very high mag. (WC/Nephron)

www:

Several images of NUCC (nih.gov).^[20]

IHC

Features:

CK7 +ve CK20 +ve.
- CK20 may be negative in over 50% of cases with metastases.^[21]

UCC vs. Prostate:

UCC: p63+, PSA-, PSAP-, CK7+, CK20+.
Prostate: p63-, PSA+, PSAP+, CK7-, CK20-.

UCC vs. RCC:

UCC: p63+.^[22]

Molecular

Not used for diagnosis.

Changes:

9p deletion -- site of CDKN2A^[23] (AKA p16).
17p deletion -- site of PT53 (AKA p53).

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High grade UCC

URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): 
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT LEAST INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.

Nested variant

 URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- INVASIVE LOW-GRADE UROTHELIAL CARCINOMA, NESTED VARIANT.
- TUMOUR PRESENT AT EDGE OF TISSUE.
- NO MUSCULARIS PROPRIA IDENTIFIED.

Papillary urothelial lesions

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

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

Key characteristics:

Nuclear - size/pleomorphism.
Papillae branching.
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.^[12]
No mitoses.
Thickness < 7 cells.^{[citation needed]}

DDx:

Inverted urothelial papilloma

AKA inverted 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,^[24] 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.^[25]
Nests have peripheral palisading of nuclei - important.

DDx:

Low grade papillary urothelial carcinoma with an inverted growth pattern.

Images

Inverted papilloma - high mag. (WC/Nephron)
Inverted papilloma - intermed. mag. (WC/Nephron)

IHC

May be useful versus inverted growth pattern UCC:^[26]

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

Papillary urothelial neoplasm of low malignant potential

Abbreviated PUNLMP.
- This is pronounced pun-lump.

General

Uncommon: prevalence ~ 0-3.5%.^[27]
PUNLMP vs. low grade papillary urothelial carcinoma has a poor inter-rater reliability.^[28]

Treatment:

Excision and on-going follow-up - like non-invasive low grade papillary urothelial carcinoma (LGPUC).^[29]
- Cheng et al. have advocated abandoning the term as they are treated like LGPUCs.^[30]

Microscopic

Features:^[5]

Rare fused papillae.
Infrequent mitoses.
Nuclei larger than papilloma - but monotonous.^[31]

DDx:

Images

PUNLMP - low mag. (WC/Nephron)
PUNLMP - high mag. (WC/Nephron)

Low-grade papillary urothelial carcinoma

Abbreviated LGPUC.^[32]
AKA low-grade papillary urothelial cell carcinoma.

Main article: Low-grade papillary urothelial carcinoma

High-grade papillary urothelial carcinoma

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

Main article: High-grade papillary urothelial carcinoma

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	^[33]
Polypoid cystitis	wide base, height > base	papillary cystitis, bullous cystitis	^[34]
Bullous cystitis	wide base, height < base	papillary cystitis, polypoid cystitis	^[34]
Papillary cystitis	narrow base, height > base	polypoid cystitis, bullous cystitis	^[34]
Interstitial cystitis	+/-ulceration (uncommon) - requires clinical correlation	urothelial CIS	^[35]
Follicular cystitis	lymphoid follicles	non-Hodgkin lymphoma	^[36]
Infectious cystitis	dependent cause (bacterial, viral, fungal)		^[37]
Granulomatous cystitis	granulomas	tuberculosis, schistosomiasis, fungal infection, post-BCG	^[37]
Radiation cystitis	edema, vascular congestion, +/- erosions -- acute; fibrosis in LP and detrusor -- chronic		^[38]

Interstitial cystitis

AKA painful bladder syndrome.^[39]^[40]

General

Chronic cystitis, culture negative.
Treatment difficult.^[39]

Epidemiology:^[40]

Women > men.

Symptoms:^[40]

Urgency.
Frequency.
Pain.

Microscopic

Features:^[35]

+/-Ulceration (uncommon).

Note:

Diagnosis requires clinical correlation.

DDx:

Urothelial CIS.

Follicular cystitis

Microscopic

Features:^[36]

Lymphoid follicles in the lamina propria.

DDx:

Non-Hodgkin lymphoma.

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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:^[34]

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

DDx:

Papillary cystitis - not a broad base.
Bullous cystitis.

Image:

Polypoid cystitis (webpathology.com).

von Brunn nests

General

Benign.

Microscopic

Features:^[41]

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

Note:

Nests should not extend into the muscularis propria.

DDx:

Nested urothelial cell carcinoma.^[42]
Inverted papilloma.
Cystitis cystica - have lumens, may be focal.

IHC

Features:^[42]

p53 -ve.
MIB-1 <3%.

Cystitis cystica

General

Benign.
Can be thought of as von Brunn nests with cystic change.^[43]
Called ureteritis cystica if it happens in a ureter.
- There is also a urethritis cystica - seen in the urethra.^[44]

Microscopic

Features:^[41]

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:

Nested urothelial carcinoma.^[45]

Image:

Cystitis cystica (webpathology.com).

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

Cystitis glandularis

Cystitis cystica et glandularis redirects to here.

General

Benign.
Can be thought of as cystitis cystica with mucin-secreting cells lining the cystic spaces.^[43]
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.^[46]^[47]

Microscopic

Features:^[41]

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.^[43]

Note:

Nests should not extend into the muscularis propria.

Image:

Cystitis glandularis (webpathology.com).

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

Main article: Malakoplakia

Nephrogenic adenoma

AKA mesonephric adenoma.
AKA nephrogenic metaplasia.

Main article: Nephrogenic adenoma

References

↑ JS. 9 June 2010.
↑ 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.
↑ 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.
↑ 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.
↑ ^5.0 ^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.
↑ GAG. 26 February 2009.
↑ 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.
↑ URL: http://content.nejm.org/cgi/content/full/343/17/1268. Accessed on: 27 May 2010.
↑ 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.
↑ 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.
↑ ^11.0 ^11.1 Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-57. ISBN 978-1931884280.
↑ ^12.0 ^12.1 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.
↑ Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-55. ISBN 978-1931884280.
↑ Lopez-Beltran, A.; Jimenez, RE.; Montironi, R.; Patriarca, C.; Blanca, A.; Menendez, CL.; Algaba, F.; Cheng, L. (Nov 2011). "Flat urothelial carcinoma in situ of the bladder with glandular differentiation.". Hum Pathol 42 (11): 1653-9. doi:10.1016/j.humpath.2010.12.024. PMID 21531007.
↑ Yin, H.; He, Q.; Li, T.; Leong, AS. (Sep 2006). "Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium.". Appl Immunohistochem Mol Morphol 14 (3): 260-5. PMID 16932015.
↑ Sternberg, SE. Histology for Pathologists. P.2047.
↑ Bochner, BH.; Nichols, PW.; Skinner, DG. (Mar 1995). "Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder.". Urology 45 (3): 528-31. doi:10.1016/S0090-4295(99)80030-2. PMID 7879346.
↑ URL: http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html. Accessed on: 19 August 2011.
↑ Talbert, ML.; Young, RH. (May 1989). "Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases.". Am J Surg Pathol 13 (5): 374-81. PMID 2712189.
↑ Terada, T. (Oct 2011). "Nested variant of urothelial carcinoma of the urinary bladder.". Rare Tumors 3 (4): e42. doi:10.4081/rt.2011.e42. PMC 3282447. PMID 22355497. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/.
↑ Jiang, J.; Ulbright, TM.; Younger, C.; Sanchez, K.; Bostwick, DG.; Koch, MO.; Eble, JN.; Cheng, L. (Jul 2001). "Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.". Arch Pathol Lab Med 125 (7): 921-3. doi:10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2. PMID 11419977.
↑ Langner, C.; Ratschek, M.; Tsybrovskyy, O.; Schips, L.; Zigeuner, R. (Aug 2003). "P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors.". J Histochem Cytochem 51 (8): 1097-9. PMID 12871991.
↑ Online 'Mendelian Inheritance in Man' (OMIM) 600160
↑ THvdK. 21 June 2010.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ ^34.0 ^34.1 ^34.2 ^34.3 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.
↑ ^35.0 ^35.1 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.
↑ ^36.0 ^36.1 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.
↑ ^37.0 ^37.1 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.
↑ 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.
↑ ^39.0 ^39.1 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.
↑ ^40.0 ^40.1 ^40.2 French, LM.; Bhambore, N. (May 2011). "Interstitial cystitis/painful bladder syndrome.". Am Fam Physician 83 (10): 1175-81. PMID 21568251.
↑ ^41.0 ^41.1 ^41.2 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.
↑ ^42.0 ^42.1 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.
↑ ^43.0 ^43.1 ^43.2 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

[1] JS. 9 June 2010.

[pmid19160695-2] 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.

[Ref_WMSP310-5] 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.

[pmid16413342-7] 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.

[pmid21419447-9] 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.

[pmid19762067-10] 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.

[Ref_Amin2-57-11] 11.0 ^11.1 Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-57. ISBN 978-1931884280.

[Ref_GUP161-12] 12.0 ^12.1 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.

[13] Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-55. ISBN 978-1931884280.

[14] Lopez-Beltran, A.; Jimenez, RE.; Montironi, R.; Patriarca, C.; Blanca, A.; Menendez, CL.; Algaba, F.; Cheng, L. (Nov 2011). "Flat urothelial carcinoma in situ of the bladder with glandular differentiation.". Hum Pathol 42 (11): 1653-9. doi:10.1016/j.humpath.2010.12.024. PMID 21531007.

[pmid16932015-15] Yin, H.; He, Q.; Li, T.; Leong, AS. (Sep 2006). "Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium.". Appl Immunohistochem Mol Morphol 14 (3): 260-5. PMID 16932015.

[16] Sternberg, SE. Histology for Pathologists. P.2047.

[pmid7879346-17] Bochner, BH.; Nichols, PW.; Skinner, DG. (Mar 1995). "Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder.". Urology 45 (3): 528-31. doi:10.1016/S0090-4295(99)80030-2. PMID 7879346.

[18] URL: http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html. Accessed on: 19 August 2011.

[pmid2712189-19] Talbert, ML.; Young, RH. (May 1989). "Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases.". Am J Surg Pathol 13 (5): 374-81. PMID 2712189.

[pmid22355497-20] Terada, T. (Oct 2011). "Nested variant of urothelial carcinoma of the urinary bladder.". Rare Tumors 3 (4): e42. doi:10.4081/rt.2011.e42. PMC 3282447. PMID 22355497. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/.

[pmid11419977-21] Jiang, J.; Ulbright, TM.; Younger, C.; Sanchez, K.; Bostwick, DG.; Koch, MO.; Eble, JN.; Cheng, L. (Jul 2001). "Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.". Arch Pathol Lab Med 125 (7): 921-3. doi:10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2. PMID 11419977.

[22] Langner, C.; Ratschek, M.; Tsybrovskyy, O.; Schips, L.; Zigeuner, R. (Aug 2003). "P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors.". J Histochem Cytochem 51 (8): 1097-9. PMID 12871991.

[omim600160-23] Online 'Mendelian Inheritance in Man' (OMIM) 600160

[24] THvdK. 21 June 2010.

[pmid19433293-25] 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.

[pmid18043040-26] 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.

[pmid19346063-27] 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.

[pmid17095142-28] 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.

[pmid16697785-29] 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.

[pmid22542126-30] 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.

[Ref_GUP170-31] 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.

[pmid22857755-32] 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.

[Ref_GUP113-33] 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.

[Ref_GUP120-34] 34.0 ^34.1 ^34.2 ^34.3 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.

[Ref_GUP124-35] 35.0 ^35.1 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.

[Ref_GUP122-36] 36.0 ^36.1 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.

[Ref_GUP127-37] 37.0 ^37.1 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.

[Ref_GUP138-38] 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.

[pmid21609485-39] 39.0 ^39.1 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.

[pmid21568251-40] 40.0 ^40.1 ^40.2 French, LM.; Bhambore, N. (May 2011). "Interstitial cystitis/painful bladder syndrome.". Am Fam Physician 83 (10): 1175-81. PMID 21568251.

[Ref_PBoD1028-41] 41.0 ^41.1 ^41.2 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.

[pmid12960809-42] 42.0 ^42.1 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.

[Ref_WMSP304-43] 43.0 ^43.1 ^43.2 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.

[pmid22397870-44] 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.

[pmid19800100-45] 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.

[pmid11104631-46] 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.

[pmid17825180-47] 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.

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Urothelium

Normal urothelium

Gross

Extent of urothelium

Urethra in males

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Malakoplakia