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Rare Solid Cancers: An Introduction - Slide 10 - V. Kataja - Rare urological cancers
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Rare Solid Cancers: An Introduction - Slide 10 - V. Kataja - Rare urological cancers

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  • Rare Cancer = rare in location / rare histology in a common location
  • Histology matters! Prognosis defined by histopathological subtype

Rare Solid Cancers: An Introduction - Slide 10 - V. Kataja - Rare urological cancers Rare Solid Cancers: An Introduction - Slide 10 - V. Kataja - Rare urological cancers Presentation Transcript

  • Rare Urological Cancers Professor Vesa V Kataja Head of Department Cancer Center, UEF / KUH Kuopio, FINLAND Kuopio University Hospital
  • Rare Renal Cancers
    • different genetic abnormalities  different histologic subtypes  different clinical presentations
    Human renal epithelial neoplasms – genetic traits Histology Clear cell Papillary type 1 Papillary type 2 Chromophobe Oncocytoma Frequency 75 % 5 % 10 % 5 % 5 % Gene VHL Met FH Birt-Hogg-Dube ’ Clinical presentation - tumours in multiple organs - 40 % deve-lop RCC - HPRC , bilateral, multifocal papillary renal carcinoma - HLRCC , cutaneous or uterine leiomyoma - often aggressive - fibrofolliculoma, pulmonary cysts, multifocal and bilateral renal tumours (oncocytic 50 % chromo-phobic 33 %, clear cell 10 %, onco-cytoma 7 %)
  • Rare Renal Cancers 15 % Histological subtypes of sporadic renal cell cancer Histology Prognosis Note
      • Clear cell 75 %
    70 % @ 5 yrs Mutated VHL common Papillary type 1 80 % @ 10 yrs Papillary type 2 60 % @ 10 yrs Outcome studies limited Chromophobe Good ” malignant oncocytoma” ? Oncocytoma Excellent Benign Collecting duct 14 % @ 10 yrs Rare (1 %) and aggressive Medullary Median survival 4.5 mths (95 % metastatic @ dg) Rare and very aggressive Black race, all sickle cell trait/disease, mean age 19 yrs Sarcomatoid variant Median survival 6.6 mths Rare, aggressive variant of many histological subtypes
  • Rare Renal Cancers *Not in WHO 2004 classification Histological subtypes of sporadic renal cell cancer Histology/Entity Prognosis Note
      • Mucinous tubular and spindle-cell
    Behaves mainly in low-grade fashion Female:Male = 4 : 1 Translocation carcinoma (Transcription factor TFE3, TFEB ) TFE3 have indolent course despite advanced stage @ dg Children and young adults (median age 20 yrs) Generally large @ dg Post-neuroblastoma carcinoma Not established, affects longevity of life Mean interval 9 yrs from NB to RCC (risk > 300-fold) Tubulocystic carcinoma* Not established; mainly on the better side – most pT1 @ dg Male:Female = 7:1 Subset of papillary RCC?
  • Rare Renal Cancers *Not in WHO 2004 classification Histological subtypes of sporadic renal cell cancer Histology/Entity Prognosis Note End-stage renal disease associated carcinoma* 40 – 100 x the risk of general population Depends on histopathological subtype Spectrum of recognised types Two novel neoplasia 1) Cystic disease associated RCC 2) Papillary clear cell RCC Follicular RC* Good Note! metastatic follicular carcinoma of the thyroid Clear cell papillary and cystic RCC* Excellent TFE3 negative Oncocytic papillary RCC* Not established; mainly on better side Genetically similar to papillary RCC type 1 and 2 (trisomy 7, 17, loss of Y in FISH); male predominance (87 %)
  • Umberto Capitanio et al., BJU Int 103:1496-1500;2009
  • Rare Renal Cancers
    • CARCINOID TUMOUR
      • carcinoid syndrome in 10 – 15 %
      • association to horseshoe kidney (18 – 26 %) and renal teratomas (15 %)
      • metastatic disease in 50 – 60 % (LNs, liver, bone)
      • prolonged clinical course even with metastatic disease
    Renal carcinoid with CgA positivity Mazzucchelli R., et al. BJU Int 2009
  • Rare Renal Cancers
    • SMALL CELL CARCINOMA
      • usually close to renal pelvis
      • symptoms due to tumour growth, not due to ectopic hormones
      • high mitotic count, vascular tumour emboli, tumour necrosis
      • concomitant urotelial carcinoma in 1/3
      • metastases common: brain, bone, liver, adrenal
      • prognosis pessima: 75 % die within one year
  • Rare Renal Cancers
    • LARGE-CELL NEUROENDOCRINE CARCINOMA
      • first case described in Lane BR, et al. BJU Int 2007
      • To date, three described cases
      • prognosis pessimistic = small cell carcinoma
    Large cells with intense synaptophysin positivity Dundr P et al., Pathol Oncol Res 2010
  • Cancer of the Renal Pelvis and Ureter
    • Upper urinary tract tumours are uncommon
      • mainly arising from the renal pelvis (5 % of all renal tumours)
      • male predilection 2-3:1
      • later in life, mainly in the 70’s – 80’s
      • histology TCC in 90 %; the rest SCC and adeno-carcinoma (1 %)
      • diagnosis and staging problematic and less accurate
      • in TNM unique T3 definition for cancers of renal pelvis and ureter
  • Cancer of the Renal Pelvis and Ureter - TREATMENT -
    • RADICAL APPROACH
      • Open surgery
      • laparoscopic nephro-ureterectomy
    • NON-RADICAL APPROACH
    • ureteroscopic or percutaneous resection
      • Nd:YAG laser
    Hall MC et al. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology1998;52:594 Five-Year Disease-Specific Survival by Stage after Surgical Resection of Transitional Cell Carcinoma of the Upper Urinary Tract (77 % open surgery) Stage No %
      • pTa/pTis
    38 100 pT1 99 92 pT2 34 73 pT3 53 41 pT4 19 0
  • Cancer of the Renal Pelvis and Ureter - TREATMENT -
    • Adjuvant topical therapy
      • following endoscopic resection
        • BCG (pTis)
        • Adriamycin
      • reducing / delaying recurrence
      • CAVE! Risk of systemic absorbtion greater than in the treatment of bladder cancer
    • Adjuvant combined modality therapy
      • Cisplatin chemotherapy
      • Radiation therapy (45 – 50 Gy)
      • OS 21 – 49 % @ 5 yrs
      • RCT followed by CT
      • data from phase II trials
    • Relapsed / Metastatic cancer
      • cisplatin-based CT equal to bladder cancer
  • Rare Urothelial Bladder Cancers Variants of invasive urothelial carcinoma Squamous differentiation Glandular differentiation Nested pattern Microcystic Micropapillary Lymphoepithelioma-like Plasmacytoid and lymphoma-like Sarcomatoid/carcinosarcoma Giant cell Trophoblastic differentiation Clear cell Lipid cell Undifferentiated Adapted from the World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs Compared to pure urothelial cancers: - Higher clinical stage at presentation - More likely to be invasive
  • Rare Non-urothelial Bladder Cancers
    • Squamous cell carcinoma
    • Adenocarcinoma
    • Small cell carcinoma
    • Sarcomas
    • Carcinosarcoma
    • PNET
    • MPNST
    • Hemangiopericytoma
    • Lymphomas
  • Non-urothelial Bladder Cancers
    • SQUAMOUS CELL CARCINOMA
      • 3 - 5 % of bladder cancers
      • in endemic schistosomiasis regions up to 60 %
      • more aggressive than urothelial cancer 1
      • surgery is cornerstone of treatment!
        • surgery +/- RT: combination therapy improves DFS
        • 44-49 % vs 25 % @ 5 yrs (RCT with 236 pts) 2*
        • neoadjuvant CT with epirubicin improves DFS
        • 73.5 % vs 37.9 % @ 2 yrs (RCT with 71 pts) 3*
    1 Scosyrev et al., Urology 2009 (SEER Data) 2 Zaghloul et al., IJROBP, 1992 3 Gad el Mawla et al., Ann Oncol 1991 *NOTE! Trials on bilharzial SCC
  • Non-urothelial Bladder Cancers
    • ADENOCARCINOMA
      • 1 – 2 % of bladder cancers
      • in developing world up to 11 % 1
      • urachal (10 %) vs non-urachal adenocarcinoma
        • urachal squamous or urothelial in origin
        • 5-yr survival higher in urachal SCC 2
        • urachal SCC  partial cystectomy
        • non-urachal SCC  radical cystectomy
        • 5-FU based CT beneficial(?) 3
    1 Ghaneim MA et al., J Urol 1997 2 Wright JL et al., Cancer 2006 3 Siefker-Radtke A. Expert Rev Anticancer Ther 2006 Urachus
  • Non-urothelial Bladder Cancers
    • SMALL CELL CARCINOMA
      • 0.5 - 1 % of bladder cancers
      • any degree small cell histology  small cell cancer 1
      • prognosis determined by small cell histology
      • predominantly systemic disease!
        • radical cystectomy (alone) not ideal (?)
        • chemoradiation (?)
        • systemic chemotherapy (?)
      • systemic CT  radical cystectomy reasonable approach 2
      • 8 % @ 5 yrs survival rate in local disease 3
    1 World Health Organization Classification of Tumours, 2004 2 Black PC et al., Urol Oncol 2009 3 Mackey JR et al., J Urol 1998
  • Non-urothelial Bladder Cancers
    • LYMPHOMAS
      • 5 % of the non-urothelial tumours of the urinary tract
      • less than 100 cases described in the English literature
      • more common in females
      • most are low-grade B-cell NHL of the mucosa associated lymphoid tissue, ie MALT
      • 20 % high grade, DLBCL being most common phenotype
      • treatment follows lymphoma protocols
      • prognosis favourable
  • Non-urothelial Bladder Cancers SARCOMAS Leiomyosarcoma Most common adult sarcoma in bladder. Male predominance 2:1. Post cyclophospamide (5 – 20 yrs). Aggressive neoplasm
      • Rhabdomyosarcoma
    Most common bladder malignancy of childhood and adolescence. Embryonal, botryoid and alveolar variants. Post therapy at 6.1 yrs 40 % retaining functional bladder, survival rate 82 % (not incl. those with disseminated disease @ dg) Angiosarcoma Exceedingly rare and carries a poor prognosis: 70 % die within two years. Metastases to lungs and liver frequent Malignant fibrous histiocytoma (MFH) Predominantly in men in their 50s – 80s. Often large at presentation involving full thickness of bladder wall. Very aggressive with high local recurrence rate and metastases Carcinosarcoma Malignant epithelial neoplasms with a neoplastic spindle cell component. Post RT and cyclophospamide. Alveolar soft-part sarcoma The only case identified in the bladder of a 25-year-old woman (Amin MB, et al., Am J Surg Pathol, 2006) Other sarcomas Liposarcoma, chondrosarcoma, Kaposi sarcoma, Sarcoma NOS
  • Non-urothelial Bladder Cancers OTHER Carcinoid Around 20 reported cases. Not associated with carcinoid syndrome. Submucosal. 25 % present with lymph node or distant metatases. Local disease cured by excision
      • Large cell neuroendocrine carcinoma (LCNEC)
    Anecdotal cases. Equally aggressive to small cell carcinoma Primitive neuroectodermal tumour (PNET) Rare case reports. Highly aggressive, rapidly growing! Shares the same chromosomal abnormalities with Ewing sarcoma Malignant peripheral nerve sheat tumour (MPNST) Only a few cases documented. Dg < 40 years. Associated with NF type 1, possibly originating in nerve sheat neurofibromas in autonomic nerve plexuses in bladder wall. Highly malignant. Hemangiopericytoma Rare case reports in adults in their mid-40’s. Slowly growing painless mass. Microscopically benign appearance, yet 50 % develop metastases
  • Prostate Cancer
    • > 95 % adenocarcinomas arising in acinar and proximal ductal epithelium
    • most tumours develop in peripheral zone (PZ)
      • 10 – 20 % in transitional zone
    • adenocarcinoma of the prostate is highly prevalent and clinically heterogeneous disease
    • molecular understanding emerging
    Almost all PCs show focal neuroendocrine differentiation as evident by CgA, serotonin, NSE, synaptophysin or bombesin/gastrin releasing peptide positivity
  • Rare Prostate Cancers
    • ductal carcinoma
    • small cell carcinoma
    • large cell neuroendocrine cancer (LCNEC)
    • clear cell variant carcinoma
    • mucinous adenocarcinoma
    • sarcomas
    • lymphomas
    • carcinoid tumour
  • Rare Prostate Cancers
    • DUCTAL CARCINOMA
      • in biopsies 0.4 – 0.8 % pure ductal
      • 371 ductal and 442 881 acinar carcinomas from the SEER database
      • ductal carcinomas more likely to
        • present with distant disease (12 % vs 4 %)
        • be poorly differentiated (50 % vs 32 %)
        • 30 % lower mean PSA
        • 2.4-fold increased odds for prostate specific antigen less than 4.0 ng/ml
        • 2.2-fold increased disease specific mortality in men with local-regional disease @ dg
    Morgan TM et al., J Urol 2010
  • Rare Prostate Cancers
    • SMALL CELL CARCINOMAS
      • 1 – 5 % of prostatic malignancies (mixed adeno-NEC included = 50 %)
      • some with clinically evident adrenocorticotropic and antidiuretic hormone production
      • histologically identical to SCLC
      • diagnositcally should not be assigned a Gleason grade
      • best identified by strong CD44 membrane staining
      • mean survival < 1 year
      • treatment controversial: surgery vs combination CT
  • Rare Prostate Cancers
    • CARCINOID TUMOUR
      • true carcinoid tumours exceedingly rare
      • predominantly in elderly men
      • PSA negative
      • synaptophysin positive
      • may metastasise to lymph nodes, liver, lungs and bone
      • must be distinguished from ”carcinoid-like carcinoma”, ie. conventional adenocarcinoma with neuroendocrine features
  • Rare Prostate Cancers PSA negative staining of the tumour Carcinoma strongly positive for synaptophysin
    • 34-year old man with a three year history of symptomatic chronic prostatitis and one year history of dysuria
    • developed obstructive uropathy  TURP
    • low grade neuroendocrine carcinoma
    • somatostatin scintygraphy,FDG-PET and abdominal CT scan negative for metastases
    • radical prostatovesiculectomy  pT3N1M0
    • no additional treatment
  • Rare Prostate Cancers OTHER Large cell neuroendocrine carcinoma (LCNEC) Few described. Can be mistaken for Gleason 5+5 adenocarcinoma. Strong positivity for CD56, C57, CgA, synaptophysin. Strong bcl-2 overexpression, expression of MIB-1 and p53 in > 50 % of nuclei, negative AR staining. Prognosis = small cell carcinoma
      • Clear cell variant carcinomas
    signet-ring adenocarcinoma. Aggressive, very uncommon Mucinous (colloid) adenocarcinomas Characterised by large pools of extracellular mucin that by definition compose at least 25 % of the tumor volume. Represent approximately 0.4 % of all prostate adenocarcinomas. Considered more aggressive than non-mucinous adenocarcinoma. Sarcomas Highly aggressive. Leiomyosarcoma most common (0.1 % of prostate malignancies). Therapeutic options with efficacy are limited Lymphomas Rare. often with extraprostatic disease. Presents in all possible phenotypes. Treatment according to lymphoma protocols
  • Carcinoma of the Urethra
    • Male urethral carcinoma
    • Chronic irritation
    • HPV-16 (SCC) and other infections
    • urethral stricture (25 – 75 %)
    • 80 % squamous cell
    • 15 % transitional cell
    • 5 % adeno and undifferentiated
    • NOTE! Varies with anatomical location – prostatic vs penile urethra
    • Most often in bulbomembra-neous urethra (60 %)
    • Female urethral carcinoma
    • Incidence 4-fold to males
    • Chronic irritation
    • recurrent UTI
    • 60 % squamous cell
    • 20 % transitional cell
    • 10 % adeno
    • 8 % undifferentiated
    • 2 % melanoma
    • clear cell a distinct entity
    • histology has no effect on prognosis  same treatment
  • Carcinoma of the urethra
    • Male urethral carcinoma
    • anterior: lower grade, better prognosis
    • Ta, Tis, T1  TUR
    • T2  partial amputation
      • in proximal tumours total
    • prostatic urethra  radical cystoprostatectomy with en bloc penectomy
    • advanced T3-4N1-3  multimodality treatment with neoadjuvant CT followed by surgery or RT
    • Female urethral carcinoma
    • anterior: lower grade, better prognosis
    • Ta, Tis, T1  local excision
    • T2  brachytherapy
    • proximal or bulky locally advanced  en bloc total urethrectomy, cystectomy with pelvic lymphaden-ectomy, hysterectomy with salpingectomy, and removal of the anterior wall of the vagina combined with neodjuvant CT, EBRT and brachytherapy
    • median time to relapse = 13 mths
  • Kuopio Thank you!