Part 2 Urothelial Variant Histologies
Sarcomatoid/carcinosarcomaBackground Highlights: Historically sarcomatoid carcinoma and carcinosarcoma were thought to be two distinct phenotypes; however this aggressive histology is now considered to be under the same umbrella with mesenchymal origins.
Management Notes: Due to the aggressive nature of this subtype, there is no role for intravesical therapy at any stage. Many patients go directly to cystectomy, though it's not currently known whether neoadjuvant chemotherapy is appropriate in this population. This is a group where intraoperative radiation therapy (IORT) may provide benefit, extrapolating from current principles in sarcoma surgery. 
Squamous DifferentiationBackground Highlights: This is perhaps the most common histological variant, affecting at least 16-20% of bladder cancer patients. New research has connected squamous differentiation to a distinct "basal" bladder cancer subtype that is more aggressive . These patients have p63 upregulation at presentation.
Management Notes: While much is still being discovered with regards to the squamous "basal" subtype, currently most clinicians would treat this histological variant similar to urothelial cancer with intravesical BCG for non-muscle invasive disease and pre-operative chemotherapy in muscle invasive disease.
MicropapillaryBackground Highlights: Micropapillary urothelial carcinoma is another aggressive histologic variant, closely resembling serous carcinoma of the ovary. It is likely underdiagnosed, and portains a worse prognosis.
Management Notes: There is good data to support early cystectomy, and forgo intravesical treatments in early stage micropapillary bladder cancer . Recently, new research has identified a link between the micropapillary histologic variant and the ERBB2 (HER2) genetic mutation.  This is significant because the HER2 mutation is associated with worse prognosis ; however, there are current drugs available that target the HER2 receptor, and therefore there is newfound hope that patients with HER2 mutations may benefit from early identification and treatment.
Click here to read our previous blog entry on Micropapillary Urothelial Cancer for more details.
If the current research momentum continues, this blog entry will be dated within a few years. Histologic variants will ultimately give way to molecular and genetic variants for which targeted therapies will be developed and delilvered. At Johns Hopkins and at other similar minded institutions this is the ultimate objective in treating each bladder cancer singularly and comprehensively.
Click here to read Part 1: Non-Urothelial Bladder Cancer
This blog was written by Max Kates, MD, a URO-2 resident at the Brady Urological Institute at Johns Hopkins.
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 Kamat AM, Gee JR, Dinney CP et al: The case for early cystectomy in the treatment of nonmuscle invasive micropapillary bladder carcinoma. J Urol 2006; 175: 881.
 Ross JS, Wang K, Gay LM et al: A high frequency of activating extracellular domain ERBB2 (HER2) mutation in micropapillary urothelial carcinoma. Clin Cancer Res 2014; 20: 68.
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