Bladder, ureter & renal pelvis
Squamous cell neoplasms
Squamous cell carcinoma


Minor changes: 3 August 2020

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PubMed Search: Squamous cell carcinoma [title] bladder review[ptyp]

Susan Prendeville, M.D.
Cite this page: Prendeville S. Squamous cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bladdersquamous.html. Accessed August 11th, 2020.
Definition / general
  • Malignant epithelial neoplasm arising in the urinary bladder, renal pelvis or ureter demonstrating a pure squamous cell phenotype
  • This topic describes classic squamous cell carcinoma; please see separate topic on verrucous squamous cell carcinoma
Essential features
  • Uncommon subtype of carcinoma showing pure squamous morphology without any component of conventional urothelial carcinoma
  • Predisposing factors include Schistosoma infection, smoking and conditions resulting in chronic irritation
  • May be associated with keratinizing squamous metaplasia / dysplasia of the mucosa
  • Must be distinguished from urothelial carcinoma with squamous differentiation and secondary spread of squamous cell carcinoma primary to another site, e.g. cervix, penis, anus
Terminology
  • Classic / typical squamous cell carcinoma
ICD coding
  • ICD-10: C67.9 - malignant neoplasm of bladder, unspecified
  • ICD-O: 8070/3 - squamous cell carcinoma, NOS
Epidemiology
  • Incidence varies by geographic region
  • 2 - 5% of bladder tumors in Western countries (nonbilharzial) (Arab J Urol 2016;14:183)
    • Most common nonurothelial subtype of bladder cancer
  • 20 - 30% of bladder tumors in geographic regions with high prevalence of schistosomiasis (bilharzial) including Egypt and other parts of Africa (Arab J Urol 2016;14:183)
  • Slight male predominance
Sites
  • Predilection for lateral bladder walls, dome and trigone
Pathophysiology / etiology
  • Schistosomiasis
    • Schistosoma haematobium
    • Major risk factor for bladder squamous cell carcinoma in geographic regions with high prevalence of schistosomiasis including Egypt and other parts of Africa
  • Smoking: 5x increased risk compared with nonsmokers (JAMA 2011;306:737)
  • Chronic bladder irritation / inflammation associated with:
    • Long term catheterization
    • Bladder calculi or foreign bodies
    • Neurogenic bladder
    • Bladder exstrophy
Clinical features
  • Typically presents with hematuria
  • May also have irritative urinary symptoms including dysuria, urgency and frequency
Diagnosis
  • Urine cytology
  • Cystoscopy and biopsy / transurethral resection of bladder mass
Radiology description
Radiology images

Images hosted on other servers:

MRI bladder

Solitary mass lower right kidney

Mass in right renal pelvis

Prognostic factors
Case reports
  • 45 year old woman with poorly differentiated squamous carcinoma arising on a background of recurrent condyloma acuminatum (Urol Case Rep 2016;7:61)
  • 46 year old woman with basaloid squamous cell carcinoma of the bladder and concomitant HPV infection of the genital tract (Int J Urol 2015;22:222)
  • 57 year old man with recurrent stone formation presenting with muscle invasive squamous cell carcinoma of the bladder (Clin Case Rep 2017;5:1616)
  • 61 year old woman with enterocutaneous fistula secondary to squamous cell carcinoma of the bladder (Urol Case Rep 2015;3:201)
  • 71 year old woman with Trousseau syndrome and squamous cancer of the bladder (Clin Case Rep 2018 Feb;6:653)
Treatment
  • Radical cystectomy and lymphadenectomy
  • Role of neoadjuvant chemotherapy in pure squamous cell carcinoma is uncertain
Clinical images

Images hosted on other servers:

Bladder exstrophy

Gross description
  • Usually large exophytic bulky tumor; some cases are predominantly flat with ulcerating / infiltrating appearance (Am J Surg Pathol 2007;31:1777)
  • Typically has whitish coloration
  • Often necrotic with flaky keratin material on the surface
Gross images

Bladder

Contributed by Susan Prendeville, M.D.
Cystoprostatectomy specimen

Cystoprostatectomy
specimen
Cross section of tumor

Cross section of tumor

Ulcerating tumor

Ulcerating tumor




Renal pelvis

Contributed by Nicole K. Andeen, M.D.
Dilated renal calyces due to reflux

Dilated renal calyces due to reflux

Solid, tannish white with central necrosis

Solid, tannish white with central necrosis

Microscopic (histologic) description
  • May be well, moderately or poorly differentiated
  • Irregular infiltrating nests or sheets of malignant squamous cells with destructive stromal invasion
  • Squamous differentiation in the form of keratin pearls, individual cell keratinization or intercellular bridges; findings may be focal in poorly differentiated tumors
  • Often associated with surface keratinizing squamous metaplasia and dysplasia / squamous carcinoma in situ (Am J Surg Pathol 2007;31:1777)
  • Must not show any component of conventional urothelial carcinoma or urothelial carcinoma in situ
    • If present, even focally, tumor is designated as urothelial carcinoma with squamous differentiation
Microscopic (histologic) images

Bladder

Contributed by Susan Prendeville, M.D.
Destructive stromal invasion

Destructive stromal invasion

Irregular squamous nests

Irregular squamous nests

Keratin pearls

Keratin pearls

Prominent keratinization

Prominent keratinization

Intercellular bridges

Intercellular bridges


Poorly differentiated tumor

Poorly differentiated tumor

Squamous dysplasia / carcinoma in situ

Squamous dysplasia / carcinoma in situ

Invading muscularis propria

Invading muscularis propria

Keratinizing squamous dysplasia

Keratinizing squamous dysplasia

<i>Schistosoma haematobium</i> eggs

Schistosoma haematobium eggs




Renal pelvis

Contributed by Nicole K. Andeen, M.D.
Invasive tumor

Invasive tumor

Entrapped glomeruli

Entrapped glomeruli

No urothelial differentiation

No urothelial differentiation

Individual cell keratinization

Individual cell keratinization

Entrapped renal tubules

Entrapped renal tubules

Virtual slides

Images hosted on other servers:

Cystectomy with squamous cell carcinoma

Cytology description
  • Keratinized cells demonstrate dense orangeophilic cytoplasm on Pap stain
  • Hyperchromatic nuclei with irregular nuclear membranes
  • Often necroinflammatory background
Cytology images

Contributed by Susan Prendeville, M.D.

Malignant squamous cells

Keratinized malignant cells

Positive stains
Negative stains
Molecular / cytogenetics description
  • HPV DNA in situ hybridization negative
  • Basal / squamous molecular subgroup of muscle invasive bladder cancer show frequent mutations in TP53 and RB1 (Eur Urol 2020;77:420)
Sample pathology report
  • Bladder, tumor left lateral wall, transurethral resection:
    • Invasive poorly differentiated carcinoma with extensive squamous differentiation
    • No evidence of in situ carcinoma (urothelial or squamous) in this biopsy material (see comment)
    • Comment: The differential includes pure squamous cell carcinoma and urothelial carcinoma with extensive squamous differentiation. This distinction requires evaluation of the entire resected tumor. In addition, clinical / radiological correlation is advised to ensure the tumor is compatible with a bladder primary.
  • Bladder and prostate, robotic radical cystoprostatectomy:
    • Bladder with invasive squamous cell carcinoma, moderately differentiated (see synoptic report)
    • Prostate, negative for carcinoma
Differential diagnosis
  • Urothelial carcinoma with squamous differentiation:
    • Squamous differentiation is common in urothelial carcinoma and may be extensive
    • Careful search for conventional urothelial carcinoma component or urothelial carcinoma in situ (may be focal)
    • Immunohistochemistry is of limited utility in this differential due to overlapping profiles; a panel approach may aid diagnosis in some cases: (squamous markers CK14 / desmoglein-3 with urothelial markers GATA3 / uroplakin / S100P) (Hum Pathol 2013;44:164)
  • Metastasis or direct extension of squamous cell carcinoma primary to another site, e.g. cervix, penis, anus:
    • Requires clinical and radiological correlation
    • p16 expression not of use in this differential
    • In situ hybridization for HPV DNA supports cervical primary (expressed in majority of cervical but not bladder squamous cell carcinoma) (Am J Surg Pathol 2014;38:1017)
  • Verrucous squamous cell carcinoma:
    • Well differentiated tumor showing minimal cytologic atypia
    • Hyperkeratotic papillary or undulating projections with a pushing type of invasion at the base comprising rounded, broad based tongues of epithelium
    • Absence of irregular infiltrating nests
Board review style question #1

A 65 year old man underwent radical cystectomy for a bladder mass and the entire tumor looked like the above histologic image. Which of the following is true regarding this tumor type arising in the urinary bladder?

  1. Gross examination usually shows a small tumor
  2. Hematuria is not a clinical feature
  3. It is associated with Schistosoma haematobium infection
  4. It is the most common type of bladder carcinoma
  5. Smoking is not a risk factor
Board review answer #1
C. It is associated with Schistosoma haematobium infection

Comment Here

Reference: Bladder squamous cell carcinoma
Board review style question #2
Which of the following is true about squamous cell carcinoma of the urinary bladder?

  1. It is associated with keratinizing squamous metaplasia / dysplasia of the bladder mucosa
  2. It is negative for CK5/6
  3. It is negative for p63
  4. It is the same as urothelial carcinoma with squamous differentiation
  5. p16 immunohistochemistry is reliable to distinguish between a bladder and cervical primary
Board review answer #2
A. It is associated with keratinizing squamous metaplasia / dysplasia of the bladder mucosa

Comment Here

Reference: Bladder squamous cell carcinoma
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