58 year old male with recent history of hematuria, for ... · hematuria, for which he underwent cystoscopy. A 1.5 cm papillary tumor was found in the left lateral wall of the bladder.

Case PresentationCase Presentation

• 58 year old male with recent history of hematuria, for which he underwent cystoscopy. A 1.5 cm papillary tumor was found in the left lateral wall of the bladder.

Pictures of casePictures of case

Case presentationCase presentation

• Outside diagnosis: Invasive papillary Outside diagnosis: Invasive papillary urothelial carcinoma involving urothelial carcinoma involving muscularis propria.muscularis propria.

• Referred for cystectomy for muscle Referred for cystectomy for muscle invasive disease.invasive disease.

SMA

DES

pT1 Urothelial pT1 Urothelial Carcinoma of the Carcinoma of the

Bladder: Criteria for Bladder: Criteria for Diagnosis, Pitfalls and Diagnosis, Pitfalls and Clinical ImplicationsClinical Implications

Rafael E. Jimenez, M.D.Rafael E. Jimenez, M.D.

pT1 StagepT1 Stage

• Tumor invasive Tumor invasive into lamina into lamina propria, but propria, but not the not the muscularis muscularis propria.propria.

Anatomy of the bladder wallAnatomy of the bladder wall

MM

MP

Anatomy of the bladder wallAnatomy of the bladder wall

LP

SM

TerminologyTerminology

TNMTNM Clinical- ManagerialClinical- Managerial

pTispTis

““Superficial”Superficial”Non Non

muscle-muscle-invasiveinvasive

pTapTa

pT1pT1

pT2+pT2+ ““Invasive”Invasive” Muscle- Muscle- InvasiveInvasive

Patterns of invasionPatterns of invasion

Grade of Papillary TumorGrade of Papillary Tumor

• Vast majority of pT1 Vast majority of pT1 tumors are high gradetumors are high grade

GG TaTa T1T1

11 3434 00

2a2a 191191 44

2b2b 5252 4747

33 1515 5858

Larsson et al. Scand J Urol Nephrol 37: 195-201, 2003.

Epithelial changesEpithelial changes

Stromal changesStromal changes

The Real WorldThe Real World

Diagnostic pitfallsDiagnostic pitfalls

• Underdiagnosis of pT1Underdiagnosis of pT1

• Overdiagnosis of pT1Overdiagnosis of pT1

• Overdiagnosis of pT2Overdiagnosis of pT2

Obscuring InflammationObscuring Inflammation

Deceptively bland UCDeceptively bland UC

Difficulty in diagnosisDifficulty in diagnosis

• LP invasion LP invasion frequently frequently overcalled.overcalled.

• Interpretation Interpretation differences:differences:•Tangential Tangential sectioningsectioning

•Tissue Tissue fragmentationfragmentation

•Cauterization Cauterization artifactsartifacts

StageStage OriginalOriginal ConsensusConsensus

pTapTa 51.651.6 78.778.7

pT1pT1 48.448.4 21.321.3

Bol et al. J Urol 169, 1291-1294, 2003.

CIS bon Bunn’s nestsCIS bon Bunn’s nests

Tangential sectioningTangential sectioning

Inverted growth patternInverted growth pattern

Invasion of smooth muscle, Invasion of smooth muscle, indeterminate for type of muscleindeterminate for type of muscle

SmoothelinSmoothelin

• Smooth muscle protein expressed Smooth muscle protein expressed only in terminally differentiated cells.only in terminally differentiated cells.

• Absent expression in noncontractile Absent expression in noncontractile and proliferative smooth muscle and proliferative smooth muscle fibers.fibers.

SmoothelinSmoothelin

• 100% specificity and 100% specificity and positive predictive positive predictive value in identifying MP value in identifying MP vs. MM.vs. MM.

• 10 TURBT cases with 10 TURBT cases with perfect correlation perfect correlation between smoothelin between smoothelin results and H&E results and H&E impression.impression.

Paner et al. Am J Surg Pathol, 2009Paner et al. Am J Surg Pathol, 2009

ACTIN

SMTLN

Prominent desmoplastic reactionProminent desmoplastic reaction

UnderstagingUnderstaging

Cystectomy StageCystectomy Stage

TURBTURB TaTa T1T1 T2T2 T3T3 T4T4 TotalTotal

TaTa 33 77 22 00 33 1515

T1T1 22 1010 99 2424 1010 5555

T2T2 00 22 88 2222 33 3535

TotalTotal 55 1919 1919 4646 1616 105105

Cheng et al. Am J Clin Pathol 113: 275-279, 2000.

• 43 of 55 cases (78%) were upstaged on cystectomy• Only 34% had muscularis propria

Substaging of pT1 diseaseSubstaging of pT1 disease

• Heterogeneous behavior in pT1 Heterogeneous behavior in pT1 disease has been recognized.disease has been recognized.

• Higher risk of recurrence may be Higher risk of recurrence may be associated with more extensive associated with more extensive invasive disease.invasive disease.

• Need to differentiate between focal Need to differentiate between focal vs. extensive invasion of lamina vs. extensive invasion of lamina propria.propria.

Substaging of pT1 diseaseSubstaging of pT1 disease

• Relationship to Relationship to muscularis muscularis mucosae:mucosae:

MM

MM

MP

Abnormal anatomyAbnormal anatomy

MM

BV

Substaging of pT1 diseaseSubstaging of pT1 disease

• Depth of Invasion Depth of Invasion measured by measured by micrometer:micrometer:

AuthorAuthor CategoriesCategories OutcomeOutcome EndpointEndpoint

Cheng Cheng 19991999

<1.5 mm<1.5 mm 93%93% 5-year 5-year PFSPFS

>1.5 mm>1.5 mm 67%67%

Substaging of pT1 diseaseSubstaging of pT1 disease

• Maximum linear Maximum linear size of invasive size of invasive front:front:

AuthorAuthor CategoriesCategories OutcomeOutcome EndpointEndpoint

Van Van der AA der AA 20052005

<0.5 mm (1 <0.5 mm (1 hpf hpf diameter)diameter)

69%69% 5-year 5-year PFSPFS

>0.5 mm>0.5 mm 50%50%

Clinical ManagementClinical ManagementBaseline treatmentBaseline treatment

• Transurethral resection Transurethral resection of tumor:of tumor:• Provide adequate Provide adequate

tissue for pathologic tissue for pathologic analysisanalysis

• Remove all visible Remove all visible diseasedisease

• Provide tissue from Provide tissue from MP for adequate MP for adequate staging.staging.• Repeat resection if Repeat resection if

no MP identified in no MP identified in the samplethe sample

Clinical ManagementClinical ManagementIntravesical therapyIntravesical therapy

• Progression-free Progression-free survival 40% at 5-y for survival 40% at 5-y for patients with TUR onlypatients with TUR only

• PFS improves 15-23% PFS improves 15-23% in patients treated with in patients treated with intravesical intravesical chemotherapychemotherapy

• BCG may be superior BCG may be superior in preventing in preventing recurrence and recurrence and progression, but may progression, but may be associated with be associated with worse side effects and worse side effects and higher cost.higher cost.

Tolley et al. Journal of Urology 1996;155: 1233-1238

Recurrence-free survival

Clinical ManagementClinical ManagementCystectomyCystectomy

• High risk of High risk of understaging in understaging in TURTUR

• High rate of High rate of progressionprogression

• High cure rate High cure rate associated with associated with cystectomycystectomy

Herr and Sogani. J Urol 2001; 166:231

Disease specific survival

SummarySummary

• Pathologic diagnosis of pT1 urothelial carcinoma Pathologic diagnosis of pT1 urothelial carcinoma places the patient in an unique managerial places the patient in an unique managerial category.category.

• Pathologists need to be familiarized with the Pathologists need to be familiarized with the morphologic features associated with lamina morphologic features associated with lamina propria invasion, as well as the potential pitfalls propria invasion, as well as the potential pitfalls associated with the diagnosis.associated with the diagnosis.

• Extent of the invasive component is useful Extent of the invasive component is useful information on the management of these patients; information on the management of these patients; however, currently an universally accepted however, currently an universally accepted system for substaging has not been agreed upon.system for substaging has not been agreed upon.