Squamous cell carcinoma of the bladder

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The majority of bladder cancers are transitional cell cancers.  Squamous cell carcinoma of the bladder (red and white arrows) is less common in North America.  It is often secondary to shistosomal infection (schistosoma haematobium).  It  may be associated with other types of long term irritations: chronic infections, calculi, treatment with cyclophosphamid. It occurs most often in the seventh decade with a slight male predominance. It most commonly involve the trigone and lateral walls. This patient had a long term indwelling suprapubic tube (white arrow head)  Distant metastases are infrequent (8-10%).  The prognosis is poor .Most patients die from failure of local control of the tumor.  Foci of central keratinization (keratin pearls) are seen within concentric layers of the abnormal squamous cells, occurring in the squamous cell carcinoma on the micro view (yellow arrow).

Genetics of SCCA of the bladder is complex. Chromosome 9 monosomy is an early event and might even occur in preneoplastic stages. Loss of homozygosity  is  found in particular in the locus where CDKN2/P16 sits. CDKN2/P16 is a tumor suppressor gene on chromasome 9p21. 

Loss of homozgosity is an important concept in cancer biology.  Mutant tumor suppressors genes are usually recessive (mutant oncogene are typically dominant).  Loss by deletion of the non mutant member of a homozygous  gene pair allows the mutant recessive gene to be expressed. Products of the mutant tumor supressor gene are non or less functional.  This is the TWO HIT (Knudson-Nordling) Hypothesis of cancer mutation.  One hit mutates a member of the homozygous tumor suppressor pair, the second deletes the gene that has not experienced a mutation.

References

Squamous cell carcinoma of the bladder: pathology, diagnosis and treatment.
Shokeir AA. BJU Int. 2004 Jan;93(2):216-20

A survey of homozygous deletions in human cancer genomes,. Charles Cox, Graham Bignell, Chris Greenman, Arne Stabenau, William Warren, Philip Stephens, Helen Davies, Stephen Watt, Jon Teague, Sara Edkins, Ewan Birney, Douglas F. Easton, Richard Wooster, P. Andrew Futreal, and Michael R. Stratton. PNAS March 22, 2005 vol. 102 no. 12 4542-4547