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A deeper look at what we've discovered about bladder cancer

Discoveries

Low-Grade Papillary Urothelial Carcinoma with Degenerative Atypia: A grading Pitfall

Noninvasive low-grade papillary urothelial carcinoma is a papillary neoplasm with orderly appearance and mild nuclear pleomorphism. Some cases show significant nuclear pleomorphism with degenerative atypia leading to grading difficulties. These are rare tumors characterized scattered cells with nuclei larger than 5 times the size of stromal lymphocytes but displayed smudgy chromatin and occasional multinucleation and intranuclear vacuoles. Next generation sequencing identified the following mutations: HRAS (n=4), FGFR3 (n=3), KRAS (n=3), BRAF (n=1), PDGFRA (n=1), PIK3CA (n=1). Other deleterious mutations were identified but none in genes characteristic of high-grade tumors. The combination of preservation of polarity, low mitotic activity, Ki-67 <5% with the larger atypical nuclei negative for Ki-67, along with nuclear atypia that is degenerative are features used to classify these tumors as low-grade.

Figure - High power view of thickened urothelium with scattered larger cells with degenerative chromatin

Reference
Matoso A, Parimi V, Epstein JI. Noninvasive Low-Grade Papillary Urothelial Carcinoma with Degenerative Nuclear Atypia: A Grading Pitfall. Human Pathology 2021 Apr 19:S0046-8177(21)00053-8.

Urothelial Carcinoma In Situ of the Bladder: Correlation of CK20 Expression With Adaptive Immune Resistance, Response to BCG Therapy, and Clinical Outcome

Immunohistochemical stains have been suggested to aid in diagnostically challenging cases of urothelial carcinoma in-situ (CIS). Although full thickness immunostaining for CK20 is supportive of CIS, a subset of CIS cases is CK20(-), the clinical significance of which was unknown. This study included 43 patients with primary diagnosis of bladder CIS including 32 with only CIS, 5 with CIS and separate noninvasive high-grade papillary urothelial carcinoma, and 6 with CIS and separate high-grade urothelial carcinoma with lamina propria invasion. Digital morphometric image analysis showed that the average nuclear areas of enlarged nuclei were similar in CK20(+) and CK20(-) CIS (26.9 vs. 24.5 µM2; P=0.31). Average Ki67 index for CK20(+) CIS was higher than CK20(-) CIS (31.1% vs. 18.3%; P=0.03). Patients with CK20(+) CIS [28 (65%)] and patients with CK20(-) CIS [15 (35%)] had the same rates of Bacillus Calmete-Guerin (BCG) failure but patients with CK20(-) CIS had higher stage progression [3 CK20(+) (11%) vs. 6 CK20(-) (40%); P=0.02]. Given recent approval of immune checkpoint inhibitors in patients with CIS refractory to BCG, programmed death ligand-1 expression and colocalization with CD8(+) lymphocytes was investigated as signature of adaptive immune response and was seen in 8 patients regardless of CK20 status and exclusively among patients who failed BCG. Our results confirm that negative CK20 IHC does not exclude CIS and that those patients have similar clinical outcomes as patients with CK20(+) CIS. Programmed death ligand-1 and CD8 colocalization seen among patients who failed BCG therapy is an easy assay to perform to identify patients who could potentially benefit from combined BCG therapy and immune checkpoint inhibition.

Expression of Nectin-4 in Bladder Urothelial Carcinoma, in Morphologic Variants, and Nonurothelial Histotypes

The antibody-drug conjugate enfortumab-vedotin acts by targeting nectin-4, a protein that is nearly ubiquitously expressed in conventional urothelial cancer. However, expression of nectin-4 in morphologic variants of urothelial carcinoma and nonurothelial histotypes was unknown. Immunohistochemistry for nectin-4 using was performed on 169 patients including 83 with nonmuscle invasive bladder cancer and 86 patients with muscle invasive bladder cancer. Staining was scored for intensity (0 to 3) and extent (% positive cells) using the histological score system, where >15 was considered positive. Overall, 72/83 (87%) samples of nonmuscle invasive urothelial carcinoma were positive, including 29/30 (97%) noninvasive papillary urothelial carcinomas, 7/8 (87.5%) carcinomas in situ, 36/45 (80%) papillary urothelial carcinomas invading the lamina propria. Overall, 50/86 muscle invasive tumors were positive, including 15/22 (68.2%) urothelial carcinomas, 7/10 (70%) squamous cell carcinomas, 3/11 (28%) micropapillary tumors, 4/6 (66%) adenocarcinomas, 2/4 (50%) nested carcinomas, 5/8 (63%) plasmacytoid, 1/10 (10%) sarcomatoid carcinomas, and 0/15 (0%) small cell carcinomas. Whole transcriptome RNA sequencing revealed that compared with conventional urothelial carcinomas, most sarcomatoid carcinomas and all but 2 small cell carcinomas expressed very low levels of nectin-4 mRNA but expressed significant levels of either trop2 or ERBB2, which are the molecular targets of 2 other antibody-drug conjugates-sacituzumab gavitecan (trop2) or trastuzumab deruxtecan (ERBB2/HER2). In summary, our study demonstrates that there is heterogeneity of expression of nectin-4 in morphologic variants of urothelial cancer and nonurothelial histotypes, and suggests that testing expression of nectin-4 should be considered in morphologic variants or nonurothelial histotypes found to have lower expression.

Intestinal Metaplasia Without Dysplasia in the Urinary Bladder Reveal Only Rare Mutations Associated With Colorectal Adenocarcinoma

Intestinal metaplasia (IM) is a rare finding in urinary bladder specimens. It is unclear whether IM without dysplasia is a precursor of malignancy in the urinary system. We retrospectively selected cases of IM of bladder, and performed mutation analysis for genes frequently mutated in colon cancer including BRAF, APC, KRAS, MET, NRAS, PIK3CA, CTNNB1, FBXW7, and TP53 using validated clinical tests. One IM case revealed an APC mutation and another showed an NRAS mutation. Clinical follow-up for the IM patients was available with a median follow-up of 70 months. One patient-without any mutation in the genes investigated-developed invasive bladder adenocarcinoma with intestinal differentiation with metastasis to the liver and lung. Neither of the 2 patients harboring mutations developed any malignancy. In conclusion, a minority of cases with IM without dysplasia bear mutations in the genes commonly associated with colonic adenocarcinoma, suggesting a premalignant potential for such lesions possibly following the classic multistep chromosomal instability pathway of carcinogenesis. A larger cohort of patients with longer follow-up is needed to better establish whether close follow-up is warranted for mutation-harboring IM of the bladder.

Figure - Spectrum of findings in patients with intestinal metaplasia of the bladder. A, Benign urothelium with cystitis cystica et glandularis and a focus of intestinal metaplasia without dysplasia. B, Focus of intestinal metaplasia without dysplasia and without association with cystitis cystica glandularis. C, Intestinal metaplasia with low-grade dysplasia. D, A case of adenocarcinoma with intestinal differentiation arising in association with intestinal metaplasia.

Reference
Amin A, Murati-Amador B, Lombardo KA, Jackson CL, Grada Z, Palsgrove DN, Matoso A. Analysis of Intestinal Metaplasia Without Dysplasia in the Urinary Bladder Reveal Only Rare Mutations Associated With Colorectal Adenocarcinoma. Appl Immunohistochem Mol Morphol. Nov/Dec 2020;28(10):786-790.

Adaptive immune resistance to BCG

Therapy with Bacillus Calmette-Guerin (BCG) is a form of immunotherapy where patients develop an immune response that attacks tumor cells. A proportion of patients are unresponsive to this therapy. We characterized the immune cell expression among patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guerin (BCG) and found no differences in CD4, CD8, or FoxP3 expression between responders and nonresponders. Baseline PD-L1 expression was observed in 25% to 28% of nonresponders and 0% to 4% of responders (P < 0.01). PD-L1⁺ cells in BCG nonresponders colocalized with CD8⁺ T cells. In addition, BCG therapy did not increase PD-L1 gene expression (RNA-seq) or protein levels. The number of pretreatment CD4⁺ T cells was very low among PD-L1⁺ nonresponders (12%) and high among PD-L1^- nonresponders (50%). One mechanism of BCG failure may be adaptive immune resistance. Baseline tumor PD-L1 expression predicts an unfavorable response to BCG and if validated, could be used to guide therapeutic decisions.

Figure - Colocalization of PDL1 and CD8 among BCG Nonresponders. H&E demonstrates tumor cells in Sample 1 and Sample 2 (demonstrated by the arrow). These tumor areas have evidence of both PDL1 brown staining cells as well as pink CD8+ expressing cells. Taken together, these images suggest colocalization of CD8 and PD-L1 in the tumor microenvironment.

Reference
Kates M, Matoso A*, Choi W, Baras AS, Daniels MJ, Lombardo K, Brant A, Mikkilineni N, McConkey DJ, Kamat AM, Svatek RS, Porten SP, Meeks JJ, Lerner SP, Dinney CP, Black PC, McKiernan JM, Anderson C, Drake CG, Bivalacqua TJ. Adaptive Immune Resistance to Intravesical BCG in Non-Muscle Invasive Bladder Cancer: Implications for Prospective BCG Unresponsive Trials. Clin Cancer Res. 2020 Feb 15;26(4):882-891. *Co-first author

Diagnosis of urothelial carcinoma in situ using blue light cystoscopy

Carcinoma in situ (CIS) is difficult to visualize with white light cystoscopy (WLC), whereas blue light cystoscopy (BLC) using photosensitizing agents improves detection rates. The goal of our study was to assess the sensitivity of BLC and correlate the results with final pathology diagnoses. We also focused on cases that were abnormal under BLC and had a pathology diagnosis that was suspicious, but not diagnostic of CIS. We found that BLC increases detection of CIS that would have been underdiagnosed with the conventional WLC. The lesions that were BLC+ and suspicious for CIS where from patients with previous therapy for urothelial carcinoma and the changes called “suspicious” were therapy related.

Figure - A&B. White light cystoscopy (WLC) view of an example of a small papillary lesion (left), highlighted by red fluorescence under blue light cystoscopy (BLC; right). Note the background urothelium around the small papillary lesions is seen dark and without fluorescence under BLC. C&D. WLC of flat mucosa of areas that show red fluorescence under BLC (right), indicating to the urologist the area to be biopsied. The pathology of both these examples were benign.

Reference
Pederzoli F, Murati Amador B, Samarska I, Lombardo KA, Kates M, Bivalacqua TJ, Matoso A. Diagnosis of urothelial carcinoma in situ using blue light cystoscopy and the utility of immunohistochemistry in blue light-positive lesions diagnosed as atypical. Hum Pathol. 2019 Aug;90:1-7.

Clinical Significance of Urothelial Carcinoma Ambiguous for Muscularis Propria Invasion on Initial Transurethral Resection of Bladder Tumor.

Urothelial carcinoma that invades the muscle wall (muscularis propria) has a much worse prognosis than those that are non-invasive or invade superficially. While the majority of patients can be confidently diagnosed as superficial or muscle invasive bladder cancer, a small subset of cases are difficult to classify. The purpose of this study was to evaluate the clinical significance of invasive urothelial carcinoma that is ambiguous for muscularis propria invasion (AMP) on initial transurethral resection of bladder tumor (TURBT). We evaluated all consecutive cases that were not able to be classified with TURBT and collected clinical and pathologic information during their follow-up and compared them to patients with muscle invasive disease and those with superficial bladder cancer who underwent radical cystectomy (RC). The great majority of patients with AMP on initial TURBT have advanced disease on RC and emphasizes the need for early repeat TURBT or even consideration of early cystectomy to lower the risk of worse pathological findings and to prolong survival.

Figure - Invasive urothelial carcinoma splaying thin muscle bundles where it is difficult to know with certainty whether there is muscularis propria invasion.

Reference
Hassan O, Murati Amador B, Lombardo KA, Salles D, Cuello F, Marwaha AS, Daniels MJ, Kates M, Bivalacqua TJ, Matoso A. Clinical Significance of Urothelial Carcinoma Ambiguous for Muscularis Propria Invasion on Initial Transurethral Resection of Bladder Tumor. World J Urol. 2020 Feb;38(2):389-395.

Epithelioid angiosarcoma of the bladder

Primary angiosarcoma of the bladder is very rare, with approximately 30 cases reported in the literature. Those with epithelioid morphology are even rarer, with only single-case reports published. The clinical presentation was hematuria and bladder mass in all cases. Many patients had a history of radiotherapy to the pelvis to treat prostate cancer and to treat uterine cervical cancer. The time from radiotherapy to the diagnosis of epithelioid angiosarcoma ranged from 6 to 15 years. The average size of the tumor was 4 cm. (range, 1 to 8 cm.). Morphologically, the tumors were composed of nests and sheets of highly atypical cells with high nuclear to cytoplasmic ratio, occasional intracytoplasmic lumens, and a hemorrhagic background. None of the cases showed any urothelial carcinoma component. Three patients showed in addition usual angiosarcoma in the resection specimen. The tumor involved the muscularis propria in many patients, and the prostate and seminal vesicles as well. Epithelioid angiosarcoma of the bladder is a rare malignancy that is frequently misdiagnosed as high-grade carcinoma, especially due to positive immunostaining for cytokeratins. This tumor is more frequent in older men with a history of radiotherapy to the pelvis. Morphologic features that should suggest the vascular origin of the tumor include highly atypical nuclei with interspersed erythrocytes, hemorrhagic background, and occasional intracytoplasmic lumens. Patients usually present with muscle invasive disease, and the prognosis is dismal.

Figure - Epithelioid angiosarcoma of the bladder composed of highly atypical epithelioid cells in a hemorrhagic background.

Reference
Matoso A, Epstein JI. Epithelioid Angiosarcoma of the Bladder: A Series of 9 Cases. Am J Surg Pathol. 2015;39(10):1377-82.

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Leiomyosarcoma is a rare type of cancer that affects smooth muscle tissue. These tumors are most common in the abdomen, but can occur anywhere in the body, including the uterus.

Rhabdomyosarcoma (RMS) is a rare type of cancer that forms in soft tissue — specifically skeletal muscle tissue or sometimes hollow organs such as the bladder or uterus.

A medical doctor who specializes in the management and surgery of diseases of the genitourinary tract.

A colorless crystalline solid which readily forms water-soluble polymers.

A mucous membrane

The removal and microscopic examination of a tissue sample.

Visual examination of the inside of the bladder by means of a cystoscope (Instrument that is passed through the urethra and allows visualization and biopsy of the bladder).

An imaging technique that uses beams of radiation (X-rays) to take an image of the body.

Epithelium that lines the bladder mucosa, the renal pelvis, ureters and urethra

Tubular structure that transports urine from the bladder with the urethral meatus in the vulva in women and with the urethral meatus in the glans penis in men

Tubular structure that transports urine from the renal pelvis with the bladder

The removal of tissue through the use of a cystoscope, without a surgical incision on the skin

Medical subspecialty that studies tissue abnormalities caused by diseases. Biopsies and resection specimens are read and informed by “surgical pathologists”

Carcinoma that resembles cancer originating in the skin

Vessels, connective tissue and cells providing support to epithelial cells

A multidisciplinary meeting of the physicians and caretakers involved in cancer care, including pathologists, surgical oncologists, medical oncologists, radiologists, nurses and genetic counselors to discuss the treatment plans for individual patients

A mass or a lump. A tumor mass can be nonneoplastic and be due to something like swelling or inflammation. A tumor mass can also be neoplastic, and includes both benign and malignant tumors

The process by which the body reads the code in RNA to make proteins

The process by which DNA is copied to make RNA

A type of treatment that specifically targets a single molecule or pathway involved in cancer cell growth and progression

A treatment that can reach cancer cells that have potentially spread throughout the body. Examples include chemotherapy, hormone therapy, and targeted therapy. Systemic therapies can have side effects due to effects on normal body cells, such as hair loss or gastrointestinal distress

A disease that widely affects the entire body

Any change noted by a patient that could be caused by a disease

A physician who specializes in surgical treatment (removal) of cancer

The term for the usual treatment given for a particular disease, which is based on past research and experience proving the treatment’s efficacy and safety

A measure of how much a cancer has grown and/or spread in the body (i.e., how advanced a cancer is). The most common staging system is the TNM system, which stands for Tumor, lymph Nodes, and Metastasis. Stage ranges from 0 to 4, with stage 0 being pre-invasive disease, and stage 4 being metastatic disease. The stage is often written using Roman numerals: stage 0, stage I, stage II, stage III and stage IV. Stage is a prognostic factor, such that a high stage is associated with a poorer prognosis or outcome

The process of having a second set of doctors look at your unique medical situation to provide a second opinion on the diagnosis and/or treatment plan

Cancer that arises from epithelium but transform to look like stromal origin

Cancer arising from stroma cells

RNA molecules are a copy of the genetic information encoded in DNA, and the RNA copy is then used to create proteins

A term used to describe the balance between the risk (such as side effects) and benefit of a therapy, procedure, or other course of action

Anything that increases the risk of developing a disease. For bladder cancer, these include smoking history, age and male gender

The chance or probability of developing a disease in a given period of time

A research study in which patient records and files are reviewed to look for results (outcomes) that already occurred in the past

Resident physicians are physicians who have finished medical school and are now studying a specific area in depth, such as pathology, internal medicine, surgery, pediatrics, radiology, and more

A reduction is size

Lymph nodes that drain (collect) the lymph fluid from a particular part of the body. The main regional nodes of the bladder are in the pelvis

When a cancer returns after previously having been eliminated. This can be a local recurrence in the bladder, or a distant recurrence when the cancer metastases to a new organ

A type of research study in which patients are randomly assigned into treatment groups, either to receive an experimental treatment (“intervention group”) or standard treatment (“control group”).

A physician who specializes in the use of imaging techniques, such as X-rays, mammograms, CT scans, and MRIs. This can include reviewing scans to detect a physical abnormality or mass, or for placing a needle in an exact location in order to perform a core biopsy

A treatment for some forms of cancer that uses high energy radiation to damage the DNA of the cells

Is the removal of the urinary bladder in women and the urinary bladder, prostate and seminal vesicles in men

A research study that is conducted using new patients and following their course to observe the outcome

A term used to describe continued growth of a cancer

A term that describes variation in size and shape of a cell’s nucleus

Urothelial carcinoma characterized by cells with an appearance similar to plasma cells and a pattern of single cell infiltration

A physician who specializes in the diagnosis of disease; pathologists use a microscope to examine the cells from tissue to determine if the tissue is normal or cancer

A description for how a cancer has responded to therapy, as seen under the microscope

The tissue of an organ

Cancer originated in the urothelium that forms exophytic or endophytic papillary structures (protrusions with a fibrovascular core)

Treatments given to relieve pain and symptoms rather than to cure the disease

An abnormal growth of cells that are clonal, that is, they arose from each other and share genetic material. Neoplasms can be benign or malignant

Therapy that is given to the patient before surgery to attempt to shrink the tumor size. Neoadjuvant therapy is typically chemotherapy or targeted therapy, but can also include radiation therapy

Thick muscle bundles that serve as the contractile unit that expulses the urine out during urination

Thins smooth muscle bundles located underneath the urothelium

A change in a cell’s DNA. Some mutations lead to a favorable change in a gene or a protein’s function, an unfavorable change, a loss of function, or no change at all (see also genetic mutation)

An approach to patient care that incorporates several disciplines of medicine and allows for communication between physicians and caretakers of different specialties. In bladder cancer care, this includes genetic counselors, medical oncologists, nurse navigators, pathologists, radiation oncologists, radiologists, and oncologic urologists. By sitting everyone down at one time, medical providers can better coordinate care, leading to better patient care

An imaging technique that uses a powerful magnetic field and radio waves to take pictures of tissue deep in the body

Classification of cancer based on its gene expression. There are 2 main molecular subtypes in bladder cancer, luminal and basal

The process by which a cell divides into two cells. Under the microscope, dividing cells can be identified by their exposed chromosomes (DNA)

A device used by pathologists to examine tissue on slides; the microscope magnifies the tissue so that pathologist can examine the individual cells and make a diagnosis

Morphologic variant of urothelial carcinoma forming micropapillae. It is considered a clinically aggressive deviant morphology

Tumor established in a distant place from its origin. Most common metastatic sites are lymph nodes, lungs, liver, brain, and bone

A doctor specialized in the treatment of cancer using chemotherapy, immune check point inhibitors, and targeted therapy

A lump or swelling. A mass can be due to excess fluid or an abnormal growth of cells; the growth of cells can be benign or malignant

The ‘edge’ of specimen containing a rim of normal-appearing tissue around the tumor. Pathologists evaluate the margin tissue under the microscope to see if the tumor has been entirely removed. “Negative” or clean margins means that all of the tumor was removed. “Positive” or involved margins means that the tumor was not entirely removed and additional therapy may be necessary

Cancer cells with the ability to invade surrounding tissue and with the potential to metastasize (spread) to lymph nodes and distant organs

Tumor cells entering the lymphatic system and in-route to lymph nodes

Part of the immunologic system where antigens are presented to immune cells to develop an immunologic response. In cancer, lymph nodes are where the tumor cells go after they leave the primary tumor

Cancer that is expected to progress more slowly that high-grade cancer

Cancer that has not yet spread to nearby tissues (by direct invasion) or to distant organs (by metastasis)

Connective tissue immediately underneath the urothelium

Cancer that has invaded into the stroma and can give rise to metastases

Refers to therapy applied using intravesical instillation of drugs or BCG

A pattern of growth where the cancer cells grow into (invade) the surrounding tissues (see also infiltrating)

Something that occurs during an operation. For instance, a frozen section is done intraoperatively

The result of the presence of immune cells (“inflammatory” cells) to a part of the body. Areas of the body that are inflamed often look swollen and red

A pattern of growth where the cancer cells grow into (invade) the surrounding tissues (see also invasive).

A type of treatment that uses the immune system to fight cancer; these therapies target proteins expressed by immune cells or on the cancer cell

A type of laboratory test that can detect the proteins expressed by a cell. The test uses special antibodies (“immunostains”) that each binds to a particular protein in question; the immunostain will change the color of the tissue to show whether a protein is present

The body’s natural defense against infection with microorganisms such as bacteria and viruses. The immune cells are constantly on the lookout for cells that look “foreign.” In addition to microorganism, immune cells can also recognize cancer cells as “foreign,” since the cancer cells may express abnormal proteins. In this way, the immune system can sometimes be a part of the body’s attack against cancer

Cancer that is expected to behave aggressively

Relating to appearance of cells and tissues under the microscope

The area of tissue that is seen at a microscope’s highest magnification (i.e., the most “zoomed in”)

Blood in the urine

Blood in semen

A type of dye that is applied to tissue sections so that the cells absorb the color and can be seen with the eye when looking under the microscope. This dye turns the nuclei blue and the cytoplasm pink

A histologic description of how closely the cancer cells resemble their normal cell of origin

A small, thin rectangular piece of glass where tissue slices from a biopsy or a surgical specimen are placed and stained with dye so that the tissue can be evaluated under a microscope

A mutation in DNA that is present at birth and that can be transferred from parent to child

A test of a patient’s DNA to look for specific gene mutations or other abnormalities that might cause cancer or other conditions

A change in a cell’s DNA. Some mutations lead to a favorable change in gene or protein’s function, an unfavorable change, a loss of function, or no change at all (see also mutation)

A meeting between a patient and a medical geneticist or counselor to discuss the potential impact of a genetic test result on the health of a patient and for their family

A laboratory test that analyzes the expression of multiple genes to characterize what proteins tumor cells are creating

A single sequence of DNA that codes for a protein

A method that pathologists can perform intra-operatively (i.e., while a surgery is underway) to quickly freeze a piece of tissue from the patient in order to take thin slices and make a slide to evaluate “in real time” while the surgery is still ongoing. This is sometimes performed on lymph nodes or margins to tell the surgeon whether there are cancer cells there. The results are only preliminary, however, and must be confirmed with review of the final FFPE sections

A term used to describe how fresh tissue samples are processed and stored so that slides of the tissue can be made and examined by a pathologist. The fresh tissues are “fixed” in a preservative called formalin, so that the tissues will not degrade or decompose. They are then “embedded” into paraffin wax, which means they are placed into a little block or wax similar to candle wax so that they can be easily sliced into thin slices and placed on a glass slide for a pathologist to review

The medical history of all of the biological (blood-related) members of a family; this family medical history can show patterns of shared diseases. Because you share genes with your family members, a “positive family history” of certain diseases may be considered a risk factor for an individual to develop the disease.

A positive result for a test that should actually be negative (i.e., an incorrect test result that states a person is positive for disease, which the person is actually disease-free)

A negative result for a test that should actually be positive (i.e., an incorrect test result that states a person is disease-free, which the person actually has the disease)

The layer of cells that lines the outside of the body, lines the inside of the body cavities, and lines the outside and inside of body organs. Epithelium is one of four types of tissues in the body; the other three types are connective tissue (like fat and fibrous tissue), muscle tissue, and neural/nervous system tissue. The epithelium lining each of the surfaces in the body has different names; for instance, the epithelium lining the outside of the body is called skin, and the epithelium lining the inside of the chest cavity is called the pleura. The epithelium that lines the urinary system is called urothelium

A type of cell in the body that makes up many different tissue types, including urothelium in the bladder. Epithelial cells in other parts of the body line the body surface (such as the “squamous epithelium” of the skin) and the body cavities. The epithelial cell is the cell or origin of carcinomas

Swelling of a part of the body from excess fluid

The molecule which contains all of your genes, located within a cell’s nucleus … a long, complex molecule with which your genes are encoded

Synonym with muscularis propria

The portion of a cell outside the nucleus, but still within the cell membrane

A consultation in pathology occurs when a specimen is sent to a second (or sometimes third) institution to review the findings. This can occur when other pathologists need assistance with a particularly challenging or rare case, or if a patient or clinician would like a second opinion on a case.

A study organized by a hospital, organization, or other group to systematically and thoroughly investigate a new medication, technique, or other approach to treatment. Clinical trials are extensively monitored to make sure that they are conducted in a safe, ethical, and equitable manner

Flat carcinoma that is non-invasive

drugs used to kill tumor cells

Cancer arising from epithelial cells

A neoplastic (clonal) growth of cells with the potential to metastasize (spread throughout the body). Cancers can arise from epithelial cells (“carcinomas”), melanocytes (“melanomas"), stromal or connective tissue cells (“sarcomas”), and lymphoid cells (“lymphomas and leukemias”)

Bacillus Calmette-Guérin (BCG) a live attenuated strain of Mycobacterium bovis, is currently an agent approved by the US Food and Drug Administration for primary therapy of carcinoma in situ, non-invasive papillary urothelial carcinoma, and carcinoma invading the lamina propria (stage pT1) of the bladder.

A tubular structure that carry blood both to and from various parts of the body. This includes arteries, veins, and capillaries.

Pelvic reservoir of urine.

Any chemical or protein created by the body that can be measured, and can be used to provide useful information such as whether a cancer is growing or shrinking during treatment. Biomarkers can also provide information about the prognosis of a cancer (prognostic biomarker), as well as whether a cancer will respond to certain therapies (predictive biomarker).

Non-cancerous. A benign tumor cannot invade nearby tissues or spread to other parts of the body

Tumor cells invading blood vessels to travel to a distant location and form a metastasis

Adjuvant therapy is any treatment given in addition to surgery. It can include chemotherapy, radiation therapy, or other treatment. This is in contrast to neoadjuvant chemotherapy, which is given before surgery