Novosti v urološki patologiji

44. Memorialni sestanek profesorja Janeza Plečnika Uredniki / Editors Metka Volavšek, Jera Jeruc, Boštjan Luzar, Jože Pižem, Gregor Mikuž Novosti v urološki patologiji Update in uropathology Inštitut za patologijo Medicinske fakultete v Ljubljani Ljubljana, december 2013

Zbornik predavanj ob 44. Memorialnem sestanku profesorja Janeza Plečnika z naslovom Novosti v urološki patologiji Založnik: Inštitut za patologijo, Medicinska fakulteta, Univerza v Ljubljani Uredniki: Metka Volavšek, Jera Jeruc, Boštjan Luzar, Jože Pižem, Gregor Mikuž Recenzenti: Metka Volavšek, Jera Jeruc, Gregor Mikuž Prelom in oblikovanje: Milan Števanec Naklada: 350 Tiskarna: Pleško, Ljubljana Izdano v Ljubljani, decembra 2013 CIP - Kataložni zapis o publikaciji Narodna in univerzitetna knjižnica, Ljubljana 616.6(082) MEMORIALNI sestanek profesorja Janeza Plečnika z mednarodnim simpozijem (44 ; 2013 ; Ljubljana) Novosti v urološki patologiji = Update in uropathology / XLIV. memorialni sestanek profesorja Janeza Plečnika z mednarodnim simpozijem, 5.-6. december 2013 = XLIVth Professor Janez Plečnik Memorial Meeting with International Symposium, December 5-6, 2013, Ljubljana, Slovenija ; [organizatorji] Medicinska fakulteta Univerze v Ljubljani, Inštitut za patologijo... [et al.] ; [uredniki Metka Volavšek... et al.]. - V Ljubljani : Inštitut za patologijo, Medicinska fakulteta, 2013 ISBN 978-961-6502-34-4 1. Gl. stv. nasl. 2. Vzp. stv. nasl. 3. Volavšek, Metka 4. Medicinska fakulteta (Ljubljana). Inštitut za patologijo 270335232

Profesor dr. Janez Plečnik (1875-1940) (B. Jakac, kreda, 6. 12. 1979)

MEDICINSKA FAKULTETA UNIVERZE V LJUBLJANI INŠTITUT ZA PATOLOGIJO INŠTITUT ZA ANATOMIJO INŠTITUT ZA HISTOLOGIJO IN EMBRIOLOGIJO INŠTITUT ZA SODNO MEDICINO 44. MEMORIALNI SESTANEK PROFESORJA JANEZA PLEČNIKA 44 th PROFESSOR JANEZ PLEČNIK MEMORIAL MEETING z mednarodnim simpozijem with International Symposium NOVOSTI V UROLOŠKI PATOLOGIJI UPDATE IN UROPATHOLOGY 5. 6. december 2013 / December 5 6, 2013 Medicinska fakulteta Univerze v Ljubljani / Faculty of Medicine University of Ljubljana Korytkova 2, Ljubljana, Slovenija

44. MEMORIALNI SESTANEK PROFESORJA JANEZA PLEČNIKA 44 th PROFESSOR JANEZ PLEČNIK MEMORIAL MEETING z mednarodnim simpozijem with International Symposium NOVOSTI V UROLOŠKI PATOLOGIJI UPDATE IN UROPATHOLOGY Častni predsednik / Honorary President Akademik prof. dr. Dušan Ferluga, dr. med. Organizacijski odbor / Organizing Committee Predsednik / President: Glavni tajnik / Secretary: Blagajnik / Treasurer: Jože Pižem, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Jera Jeruc, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Anja Milenković Kramer, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Člani / Members: Jože Balažic, Inštitut za sodno medicino, Medicinska fakulteta, Ljubljana Zvezdana Dolenc Stražar, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Nina Gale, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Boštjan Luzar, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Dean Ravnik, Inštitut za anatomijo, Medicinska fakulteta, Ljubljana Alenka Vizjak, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Metka Volavšek, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Ruda Zorc-Pleskovič, Inštitut za histologijo in embriologijo, Medicinska fakulteta, Ljubljana Tehnična tajnica / Technical Secretary: Vlasta Krfogec, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Znanstveni odbor / Scientific Committee Predsednik / President: Metka Volavšek, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Člani / Members: Nina Gale, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Jera Jeruc, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Boštjan Luzar, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Gregor Mikuž, Institute of pathology, University of Innsbruck Jože Pižem, Inštitut za patologijo, Medicinska fakulteta, Ljubljana Nina Zidar, Inštitut za patologijo, Medicinska fakulteta, Ljubljana

Seznam avtorjev Ferran Algaba Pathology unit, Fundació Puigvert, Universitat Autónoma de Barcelona, Calle Cartagena 340-350, E-08025 Barcelona, Spain Armin Alibegović Institute of Forensic Medicine, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia B. Andrejić Višnjić Department of Histology and Embryology, Medical Faculty, Novi Sad, University of Novi Sad, Serbia Lenka Bauerová Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University Prague, Czech Republic Jure Bizjak Univerzitetni klinični center Ljubljana, Klinični oddelek za urologijo, Zaloška cesta 7, SI-1000 Ljubljana, Slovenija Julija Blatnik Institute of Pathology, Faculty of Medicine University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Magdalena Bogdanovska-Todorovska Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Ana Bravc General Hospital Slovenj Gradec, Gosposvetska cesta 1, SI-2380 Slovenj Gradec, Slovenia Damjana Breznik Department of Pathology, General Hospital Murska Sobota, Rakičan, Ul. dr. Vrbnjaka 6, SI-9000 Murska Sobota, Slovenia Tatjana Bujas Department of Pathology, University Medical Centre Maribor, Ljubljanska 5, SI-2000 Maribor, Slovenia Liang Cheng Departments of Pathology and Laboratory Medicine, and Urology, Indiana University School of Medicine, Indianapolis, USA S. Cirovic Institute of Pathology, Medical Faculty, University of Belgrade Matilda Djolai Institute for Pathology and Histology, Clinical Centre of Voivodina, Novi Sad, Serbia; Department of Histology and Embryology, Medical Faculty, Novi Sad, University of Novi Sad, Serbia Ivan Domazetovski Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Blagica Dukova Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Pavel Dundr Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University Prague, Czech Republic Dejan Đorđevic Clinical Center of Serbia, Urology Clinic Gordana Đorđević Department of Pathology, School of Medicine, University of Rijeka David Garner Integrative Oncology Department, BC Cancer Agency, Vancouver, Canada V

Silvia Gasparrini Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy Damjan Glavač Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, Korytkova 2, SI-1000 Ljubljana, Slovenia Helena Gutnik Institute of Pathology, Faculty of Medicine University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia I. Hadžisejdić Department of Pathology, School of Medicine, University of Rijeka Gregor Haring Institute of Forensic Medicine, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Vesna Janevska Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Anja Jeričević General Hospital Jesenice, Cesta maršala Tita 112, SI-4270 Jesenice, Slovenia Jera Jeruc Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Vesna Jurčić University of Ljubljana, Faculty of Medicine, Institute of Pathology, Korytkova 2, SI-1000 Ljubljana, Slovenia Rajko Kavalar Department of Pathology, University Medical Centre Maribor, Ljubljanska 5, SI-2000 Maribor, Slovenia Andreja Klevišar Ivančič Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Andrej Kmetec Klinični oddelek za urologijo, UKC Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenija Tomaž Kocjan Klinični oddelek za endokrinologijo, diabetes in bolezni presnove, Univerzitetni klinični center Ljubljana, Zaloška 7, SI-1525 Ljubljana, Slovenija Selim Komina Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Robert Kordič Department of Urology, University Medical Centre Ljubljana, Zaloška 7, SI-1000 Ljubljana, Slovenia Slavica Kostadinova-Kunovska Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Mile Kovačević University clinic for pulmonary diseases and allergology Golnik, Golnik 36, SI-4204 Golnik, Slovenia Elvira Krovinović Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Bojan Labachevski Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Neža Lebič Belcijan Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Šlajmerjeva ulica 3, SI-1000 Ljubljana, Slovenia Andreja Legen Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia VI

Antonio Lopez-Beltran Unit of Anatomical Pathology, Department of Surgery and Pathology, University of Cordoba, Faculty of Medicine, Avda. Menendez Pidal s/n, E-14004, Cordoba, Spain D. Markić Urology Clinic, Clinical Hospital Center, Rijeka J. Markovic-Lipkovski Institute of Pathology, Medical Faculty, University of Belgrade; Clinical Center of Serbia, Department for Pathology Roberta Mazzucchelli Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy Marija Meznarič Institute of Anatomy, Faculty of Medicine University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Miro Mihelič Univerzitetni klinični center Ljubljana, Klinični oddelek za urologijo, Zaloška cesta 7, SI-1000 Ljubljana, Slovenija Gregor Mikuž Institute of Pathology, Medical University Innsbruck, Austria Jernej Mlakar Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Rodolfo Montironi Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy Maja Mušič Oddelek za radiologijo, Onkološki inštitut Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenija Srdjan Novaković Oddelek za molekularno diagnostiko, Onkološki inštitut Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenija Alenka Oblak Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Zdenka Ovčak Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Gordana Petrushevska Institute of Pathology, Medical faculty, University "Ss. Cyril and Methodius", Skopje, Macedonia Jože Pižem Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Jelena Podolski Department of Pathology, University Medical Centre Maribor, Ljubljanska 5, SI-2000 Maribor, Slovenia Boris Pospihalj Oddelek za patologijo, Splošna bolnišnica Slovenj Gradec, Gosposvetska 1, SI-2380 Slovenj Gradec, Slovenia Sandi Poteko Urološki oddelek, Splošna bolnišnica Celje, Oblakova ul. 5, SI-3000 Celje, Slovenia Stefano Racchini Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy Jelena Ilić Sabo Institute for Pathology and Histology, Clinical Centre of Voivodina, Novi Sad, Serbia; Department of Histology and Embryology, Medical Faculty, Novi Sad, University of Novi Sad, Serbia Skender Saidi University Surgical Clinic of Urology, University Clinical Centre "Mother Theresa, Macedonia VII

Daja Sajnkar Department of Pathology, General Hospital Celje, SI-3000 Celje, Slovenia Marina Scarpelli Pathologic Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, I-60126 Torrette, Ancona, Italy Boris Sedmak Klinični oddelek za urologijo, UKC Ljubljana, Zaloška c. 2, SI-1000 Ljubljana, Slovenija Saša Simčič Laboratory for Humoral Immunity, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana Sotir Stavridis University Surgical Clinic of Urology, University Clinical Centre "Mother Theresa, Macedonia Igor Sterle Klinični oddelek za urologijo, UKC Ljubljana, Zaloška c. 2, SI-1000 Ljubljana, Slovenija Margareta Strojan Fležar Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Barbara Šegedin Institute of Oncology Ljubljana, Department of Radiation Oncology, Zaloška 2, SI-1000 Ljubljana, Slovenia Boštjan Šeruga Sektor internistične onkologije, Onkološki inštitut Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenija S. Štifter Department of Pathology, School of Medicine, University of Rijeka Simona Šramek Zatler Department of Pathology, General Hospital Celje, SI-3000 Celje, Slovenia Peter Štrafela Department of Pathology, University Medical Centre Maribor, Ljubljanska 5, SI-2000 Maribor, Slovenia Klara Tostovršnik Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Sandra Trivunić Dajko Institute for Pathology and Histology, Clinical Centre of Voivodina, Novi Sad, Serbia; Department of Pathology, Medical Faculty, Novi Sad, University of Novi Sad, Serbia Mojca Velikonja Univerzitetni klinični center Ljubljana, Ginekološka klinika, Šlajmerjeva 3, SI-1000 Ljubljana, Slovenia Dubravka B. Vidmar Klinični inštitut za radiologijo, UKC Ljubljana, Zaloška c. 7, SI-1525 Ljubljana, Slovenia Damjan Vidovič Department of Pathology, University Medical Centre Maribor, Ljubljanska 5, SI-2000 Maribor, Slovenia J. Vjestica Institute of Pathology, Medical Faculty, University of Belgrade Gregor Vlačić Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia Metka Volavšek Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia M. Zivotic Institute of Pathology, Medical Faculty, University of Belgrade VIII

Predgovor Letošnji že 44. Memorialni sestanek profesorja Janeza Plečnika z naslovom»novosti v urološki patologiji«zajema široko strokovno področje diagnostike bolezni sečil in moških spolnih organov, zaradi anatomske bližine pa tradicionalno vključuje tudi bolezenske spremembe nadledvičnic. Na srečanju so predstavljeni novosti in napredek stroke v zadnjih letih, tako v odkrivanju, prepoznavanju in zdravljenju tumorjev urogenitalnih organov kot tudi razumevanju mehanizmov njihovega nastanka. Predstavljajo jih številni ugledni domači in tuji strokovnjaki, ne samo patologi in citopatologi, ampak tudi urologi, internisti, onkologi, radiologi, radioterapevti in molekularni biologi. Vsi so se prijazno odzvali našemu vabilu za sodelovanje, njihovi prispevki v zborniku pa bodo še dolgo v pomoč pri vsakodnevnem delu. Zaradi širine področja in predvsem znatnega napredka tako v diagnostiki kot tudi zdravljenju tumorjev s področja urološke patologije, smo program letošnjega mednarodnega znanstvenega simpozija razdelili v več sklopov. V prvem z vseh zornih kotov predstavljamo napredek stroke na področju karcinoma prostate, ki je najpogostejši maligni tumor moških in tako ena najpogostejših bolezni, s katerimi se srečujejo bolniki in zdravniki različnih specialnosti. Zaradi zgodnjega odkrivanja in sodobnih diagnostičnih ter terapevtskih metod se umrljivost zaradi raka prostate znižuje, s tem pa povečujeta pomen skrbnega spremljanja bolnikov in tesnega sodelovanja med kliniki in patologi. Poleg morfoloških značilnosti raka, njegovih posnemovalcev ter priporočil za rutinsko diagnostiko in spremljanje bolnikov, so predstavljeni sodobni kirurški in radioterapevtski pristopi ter spremembe v prostati, nastale po različnih načinih zdravljenja. Drugi sklop z novostmi s področja patologije tumorjev ledvic vključuje napovedne dejavnike metastatskega karcinoma in citopatološko korelacijo pri redkih vrstah tumorjev ledvic. Ker je bilo v zadnjem desetletju na novo opisanih precej entitet, katerih obstoja, molekularnih značilnosti ter posebnosti v kliničnem poteku se še premalo zavedamo, smo v programu vključili tudi te. V tretjem sklopu, posvečenem urotelnim tumorjem, ki večinoma prizadanejo sečni mehur, čeprav lahko vzniknejo tudi v drugih delih sečil, prav tako predstavljamo redke entitete pa tudi molekularne označevalce urotelnega karcinoma. Posebno pozornost smo namenili preneoplastičnim in predinvazivnim spremembam sluznice mehurja, ki v vsakodnevni diagnostiki patologu predstavljajo velik izziv, nič manjši izziv pa ni določanje stopnje malignosti in globine invazije urotelnega karcinoma, ki pomembno vplivata na klinično ukrepanje. Zaradi splošnega pomena zaledenelih rezov, katerih vloga se v urološki patologiji zelo razlikuje glede na pregledovan organ in specifično diagnozo, smo poseben sklop, skupno s tumorji testisa, namenili tudi pregledu tega področja. Pri tumorjih testisa so poleg slikovne diagnostike predstavljene novosti v patologiji ter pomen retroperitonealne limfadenektomije v njihovem zdravljenju. Zadnji sklop, poleg kliničnih značilnosti, patologije in molekularne biologije, vključuje tudi sodoben laparoskopski pristop h kirurškem zdravljenju tumorjev nadledvičnic, s katerimi se v urološki patologiji sicer ne srečujemo tako pogosto kot z boleznimi drugih organov, kar pa ne zmanjšuje njihovega pomena. V knjigo»novosti v urološki patologiji«smo vklučili tudi 24 prispevkov posterske sekcije. Ti s svojo pestrostjo od epidemiologije prek rezultatov raziskav do predstavitev zanimivih primerov zaokrožajo naš program, pomembno prispevajo k uspehu našega mednarodnega srečanja in so dobro izhodišče ter spodbuda za nadaljnje delo na področju urološke patologije. Metka Volavšek Jože Pižem IX

Preface This year's 44 th Professor Janez Plečnik Memorial Meeting with the title»update in Uropathology«covers the diagnostics in the wide field of diseases in urinary tract and male genital organs. Due to anatomical proximity and tradition, the pathological changes of adrenal glands are also included. Advances and new developments in the last years concerning early detection, identification and treatment of tumours in the urogenital region as well as mechanisms of their development are presented. Experts from Slovenia and abroad, not only pathologists and cytopathologists, but also urologists, internists, oncologists, radiologists, radiotherapists and molecular biologists have kindly accepted our invitation. Their contributions published in the proceedings will remain invaluable in routine diagnostic work. Due to diversified topics and recent advances in the field of uropathology, this year's international scientific symposium has been divided into sessions dedicated to particular organs. At the beginning of the symposium, prostatic carcinoma, the most common cancer in male and thus one of the most common diseases encountered by patients and physicians of different specialities, is covered from all possible angles, since early detection and contemporary treatment methods have decreased the mortality of prostatic cancer, and the adoption of new active surveillance programs has increased the importance of close collaboration between pathologists and clinicians. In addition to morphological characteristics of prostatic cancer and its mimics, recommendations for routine diagnostic approach and patient monitoring are presented, complemented with review of contemporary surgical and radiotherapeutic approaches, as well as post treatment changes in the prostate. The second part, update in kidney tumour pathology, includes prognostic markers of metastatic renal cancer and cyto-histopathological correlation in rare kidney tumours. To increase awareness of the expanding number of entities in renal cell neoplasia, where new distinct tumours have been described in the last decade, with peculiarities in morphology and clinical behaviour, they are included as well. The main topic in the third part are urothelial tumors, which mostly affect urinary bladder but can also occur in the other parts of the urinary tract, with emphasis on rare entities and molecular markers of urothelial carcinoma. Special attention is given to the distinction between urothelial dysplasia and carcinoma in situ, which remains challenging in the everyday routine diagnostic work. The importance of frozen sections in surgical pathology, with specific indications and limitations for their use in uropathology, has prompted us to make a joint session with testicular tumour pathology. Of the latter, in addition to imaging diagnostic techniques, update in morphology of testicular tumours, as well as the role of lymphadenectomy in their treatment are included. In the last part of the symposium, the clinical, morphological and molecular pathological characteristics of adrenal gland neoplasms are presented, complemented with presentation on the use of laparoscopic surgery. The proceedings»update in Uropathology«also include 24 extended contributions from the poster section. With variety of topics, from epidemiology to extensive studies and reports on rare entities, the presentations nicely enrich the programme of this international symposium, contributing to its success and setting a cornerstone and stimulation for further work in the field of urologic pathology. Metka Volavšek Jože Pižem XI

Vsebina / Contents LECTURES 1 Classification, histologic variants of prostate cancer Klasifikacija, redke oblike karcinoma prostate Gregor Mikuž 9 Mimickers of prostate cancer in needle biopsies Posnemovalci karcinoma prostate v igelnih biopsijah Ferran Algaba 13 Role of the pathologist in active surveillance of prostate cancer Vloga patologa pri aktivnem opazovanju bolnikov s karcinomom prostate Rodolfo Montironi, Silvia Gasparrini, Stefano Racchini, Roberta Mazzucchelli, Liang Cheng 17 Staging and reporting of prostate cancer Ocena stadija karcinoma prostate v kirurških vzorcih Boris Pospihalj 25 Modern procedures in surgical treatment of prostate cancer Sodobne metode kirurškega zdravljenja raka prostate Sandi Poteko 29 The role of radiotherapy in the treatment of localized prostate cancer Vloga obsevanja v zdravljenju lokaliziranega raka prostate Barbara Šegedin 35 Treatment related changes in the prostate and prostatic cancer Vpliv različnih vrst zdravljenja na parenhim in karcinom prostate Metka Volavšek 43 New (rare) entities in renal cell tumor pathology Nove in redke oblike tumorjev ledvičnih celic Rodolfo Montironi, Silvia Gasparrini, Stefano Racchini, Roberta Mazzucchelli, Liang Cheng 47 Renal cell carcinomas associated with Xp11.2 translocations/tfe3 gene fusions - our experience Karcinomi ledvičnih celic povezani z Xp11.2 translokacijami/fuzijami gena TFE3 - naše izkušnje Jera Jeruc, Klara Tostovršnik 55 Therapeutic and prognostic markers in metastatic renal cell carcinoma Napovedni dejavniki pri metastatskem raku ledvic Boštjan Šeruga, Jera Jeruc, Maja Mušič, Srdjan Novaković 59 Cyto-histopathological correlation in kidney tumor patology. Case presentations Cito-histopatološka korelacija v patologiji tumorjev ledvice. Prikazi primerov Margareta Strojan Fležar, Helena Gutnik, Jože Pižem, Zdenka Ovčak, Metka Volavšek 65 Rare entities in urinary bladder pathology Redke oblike karcinoma sečnega mehurja Antonio Lopez-Beltran 71 The impact of histopathological diagnosis (stage and grade) on treatment decision of bladder cancer Vpliv histopatološke diagnoze in globine invazije na zdravljenje karcinoma sečnega mehurja Miro Mihelič, Jure Bizjak 75 Dysplasia and carcinoma in situ of the urinary bladder Displazija in intraepitelijski karcinom sečnega mehurja Antonio Lopez-Beltran 83 Value of frozen sections in uropathology Pomen zaledenelih rezov v urološki patologiji Ferran Algaba XIII

89 Update in pathology of testicular tumors Novosti v patologiji tumorjev testisa Gregor Mikuž 99 Imaging diagnostic techniques in testicular pathology Slikovne preiskovalne metode v diagnostiki tumorjev testisa Dubravka B. Vidmar 103 The role of retroperitoneal lymphadenectomy in the treatment of testicular tumors Vloga retroperitonealne limfadenektomije pri zdravljenju tumorjev testisa Andrej Kmetec 109 Clinical spectrum of adrenal gland pathology Klinične značilnosti bolezni nadledvičnic Tomaž Kocjan 117 Pathologist s approach to adrenal gland tumours Patologov pristop k obravnavi tumorjev nadledvičnic Marina Scarpelli 119 Molecular diagnostics of patients with pheochromocytomas within syndromes multiple endocrine neoplasia type 2 and von Hippel-Lindau disease Molekularna diagnostika bolnikov s feokromocitomi v sklopu sindromov multiple endokrine neoplazije MEN 2 in bolezni von Hippel-Lindau Damjan Glavač 127 Laparoscopic surgery of adrenal gland Laparoskopska kirurgija tumorjev nadledvičnic Igor Sterle, Boris Sedmak POSTERS 131 Evaluation of p63/ck34βe12/amacr cocktail immunostain results in problematic prostatic needle core biopsies Analiza rezultatov IHK preiskav dvomljivih epitelnih sprememb debeloigelnih biopsij prostate Peter Štrafela, Jelena Podolski, Damjan Vidovič, Tatjana Bujas, Rajko Kavalar 135 Influence of gross specimen sampling on the incidence of incidental prostatic carcinoma finding in cistoprostatectomy specimens of patients with bladder carcinoma Vpliv vzorčenja resektata pri cistoprostatektomiji zaradi karcinoma sečnega mehurja na incidenco naključno odkritega karcinoma prostate Jernej Mlakar, Metka Volavšek 141 Concomitant fetal malformations known but still different Sočasne fetalne malformacije poznane, a vendar drugačne Matilda Djolai, Jelena Ilić Sabo, Sandra Trivunić Dajko, B. Andrejić Višnjić 143 Clear cell renal cell carcinoma with syncytial giant cells Svetlocelični karcinom ledvičnih celic s sincicijskimi velikankami L. Bauerová, P. Dundr 145 TFE3, specific marker in diagnosis of Xp11.2 translocation renal cell carcinoma. Two case reports TFE3, specifični marker za diagnozo Xp11.2 translokacijskega karcinoma ledvičnih celic. Prikaz dveh primerov J. Vjestica, S. Cirovic, M. Zivotic, D. Đorđevic, J. Markovic-Lipkovski 147 Bilateral metastatic renal synovial sarcoma. A case report Sinovijski sarkom z zasevki v obe ledvici. Prikaz primera Damjana Breznik, Metka Volavšek, Jera Jeruc 151 Renal cell carcinoma, unclassified - Renal cell carcinoma with components of chromophobe carcinoma with sarcomatoid dedifferentiation and papillary renal cell carcinoma Karcinom ledvičnih celic, neklasificiran - Karcinom ledvičnih celic sestavljen iz kromofobnega karcinoma s sarkomatoidno dediferenciacijo ter papilarnega karcinoma Ana Bravc, Metka Volavšek XIV

157 Perilobar nephroblastomatosis as an incidental finding in infant autopsy Perilobarna nefroblastomatoza kot naključna najdba pri obdukciji novorojenčka Mile Kovačević, MetkaVolavšek 161 Tumor-like clinical presentation of accumulated uromodulin (Tamm-Horsfall glycoprotein) in the ureter tissue. A case report Klinično za tumor sumljive odlage uromodulina (Tamm-Horsfallovega glikoproteina) v steno sečevoda. Prikaz primera Andreja Klevišar Ivančič, Metka Volavšek 165 Primary localized amyloidosis of the ureter. A case report Primarna lokalizirana amiloidoza sečevoda. Prikaz primera Vesna Jurčić, Robert Kordič, Jera Jeruc 169 Incidence of the urinary tract tumors in two-year period (2010 2011) at the Institute of Pathology, Faculty of Medicine, Skopje, Macedonia Incidenca tumorjev sečil v dveletnem obdobju (2010 2011) na Inštitutu za patologijo Medicinske fakultete v Skopju, Makedonija Slavica Kostadinova-Kunovska, Vesna Janevska, Selim Komina, Blagica Dukova, Magdalena Bogdanovska-Todorovska, Ivan Domazetovski, Bojan Labachevski, Skender Saidi, Sotir Stavridis, Gordana Petrushevska 175 Small cell carcinoma of the urinary bladder. A case report with review of literature Drobnocelični karcinom sečnega mehurja. Prikaz primera in pregled literature Ana Bravc, Jera Jeruc 181 Plasmacytoid urothelial carcinoma of the bladder. A case report Plazmacitoidni tip urotelnega karcinoma sečnega mehurja. Prikaz primera Daja Sajnkar, Metka Volavšek, Jera Jeruc, Simona Šramek Zatler 187 The use of image cytometry system for preview of urinary cytology specimens Uporaba slikovnega citometra za primarno pregledovanje citoloških vzorcev iz urinarnaga trakta Andreja Legen, Elvira Krovinović, David Garner, Margareta Strojan Fležar 189 Small cell carcinoma in the urinary bladder washing. A case report Drobnocelični karcinom v izpirku sečnega mehurja. Prikaz primera Alenka Oblak, Metka Volavšek, Margareta Strojan Fležar 193 Herpes simplex viral cytopathic effect in voided urine sample. A case report Citopatski efekt herpes simpleks virusa v vzorcu spontanega urina. Prikaz primera Julija Blatnik, Helena Gutnik, Margareta Strojan Fležar 195 Innervation of urinary bladder Oživčenje mehurja Marija Meznarič 203 The value of frozen section in genitourinary tract surgery. A five year analysis (2008 2012) Pomen zaledenelega reza v kirurgiji genitourinarnega trakta. Analiza podatkov v petletnem obdobju (2008 2012) Neža Lebič Belcijan, Metka Volavšek 211 Inflammatory pseudotumor arising in testis. A case report Vnetni psevdotumor testisa. Prikaz primera G. Đorđević, I. Hadžisejdić, S. Štifter, D. Markić 213 Testicular teratoma with somatic-type malignancy. A case report Teratom testisa s somatsko malignostjo. Prikaz primera Mojca Velikonja, Metka Volavšek 219 Usefulness of immunohistochemical detection of Treponema pallidum in tissue specimens. A case report and review of literature Uporabnost imunohistokemičnega odkrivanja Treponeme pallidum v tkivnih vzorcih. Prikaz primera in pregled literature Anja Jeričević, Saša Simčič, Metka Volavšek 223 Descriptive epidemiology of testicular tumors diagnosed in the years 2000 2012 at Institute of Pathology, Faculty of Medicine Ljubljana Deskriptivna epidemiologija tumorjev testisa, diagnosticiranih med leti 2000 2012 na Inštitutu za patologijo Medicinske fakultete v Ljubljani Mojca Velikonja, Metka Volavšek XV

229 Retroperitoneal lymph node dissection in testicular cancer Disekcija retroperitonealnih bezgavk pri raku testisa Gregor Vlačić, Metka Volavšek 235 Testicular morphology in hypogonadotropic hypogonadism after abuse of anabolic steroids. A case report Morfologija testisov pri hipogonadotropnem hipogonadizmu po zlorabi anabolnih steroidov. Prikaz primera Armin Alibegović, Gregor Haring, Metka Volavšek XVI

LECTURES

Classification, histologic variants of prostate cancer Klasifikacija, redke oblike karcinoma prostate Gregor Mikuž Institute of Pathology, Medical University Innsbruck, Austria ABSTRACT Apart from the typical acinar morphology observed in more than 90% of prostatic adenocarcinomas, a spectrum of morphological variants and prostate cancer subtypes exists. Two nosologically different groups are distinguished: the variants of conventional acinar cancer and cancers with histological pattern, which are unusual for the prostate. Variants of conventional prostate cancer (pseudohyperplastic, foamy gland, hypernephroid, atrophic, microcystic, with Paneth-cell like changes, with collagenous micronodules, with glomeruloid formations, oncocytic) do not have any known prognostic significance and are graded according to Gleason. Unusual cancer types (ductal carcinoma, mucinous {colloid} carcinoma, mucinous signet ring cell carcinoma, small cell carcinoma, sarcomatoid carcinoma and carcinosarcoma, pleomorphic giant cell carcinoma, squamous and adenosquamous carcinoma, basal cell and adenoid-cystic carcinoma, lymphoepithelioma-like carcinoma, primary urothelial carcinoma of the prostate) have mostly a very poor prognosis and are therefore real nosological entities. Key words acinar, variants, unusual cancer, Gleason grading, nosologic entities IZVLEČEK Poleg običajnega acinarnega raka prostate, ki ga srečamo v več kot 90% primerov, obstoja širok spektrum morfoloških variant. Razlikujemo lahko dve nozološko različni skupini: variante konvencionalnega raka prostate in rak z mikromorfologijo, ki je za prostato zelo redka oziroma nenavadna. Variante (pseudohiperplastični, hipernefroidni, atrofični in mikrocistični rak, rak s Panethovimi celicami, s puhljičastimi celicam, s kolagenskimi vozliči, z glomeruloidnimi strukturami in z onkociti) potekajo klinično kot običajni rak in jih lahko tudi gradiramo po Gleasonu. V nasprotju z variantami imajo redke oblike (karcinom prostatičnih vodov, mucinozni, pečatnocelični, drobnocelični nevroendokrini karcinom, ploščatocelični in bazaloidni oziroma adenoidno-cistični karcinom ter primarni urotelni karcinom prostate) v glavnem zelo slabo prognozo in so zato prave nozološke entitete. Večine redkih vrst karcinomov se tudi ne da gradirati po Gleasonu. Ključne besede acinarni, variante, redke oblike raka, določanje stopnje Gleason-a, nozološka entiteta Introduction More than 90% of diagnosed prostate carcinomas (PC) belong histologically to the acinar (microacinar, conventional) type. The remaining few percent can be sub-divided into two main groups: the variants of conventional acinar cancer (Table 1) (2) and cancers with histological patterns which are unusual for the prostate 1 (Table 2). Variants of conventional PC do not have any known prognostic significance and are graded according to Gleason, whereas cancers of unusual types have mostly a very poor prognosis (3) and are therefore real nosological entities. Because of their rarity, it is important for pathologists to be able to recognize these tumor types, accurately diagnose them, and when applicable, grade these tumors 1 In the pertinent literature the terms variant or variation are sometimes used for the unusual types and vice versa or as synonyms, which is rather confusing. and understand their prognostic and therapeutic implications. Acinar (conventional) prostate cancer The morphology of the conventional PC is well known to all pathologists. The histological features range from well-differentiated glands resembling normal prostate tissue to completely undifferentiated tumors with cells ordered in sheets or solid complexes. Small cancers are usually uniform, whereas the large cancers are multiform with different gland architecture and differentiation grade. However, all PC have in common a single tumor cell type and the absence of the basal cells. This fact is very useful in distinguishing normal glands from the carcinomatous one. Basal cells stain immunohistochemically with high molecular weight cytokeratin, p63, cytokeratins and cytokeratin 5/6 whereas PC cells do not. In contrast, PC-cells show a PSA and α-metyl-coa-racemase (AMACR) immunoreactivity (2). 1

Prostate cancer variants Table 1. Variants of conventional PC without clinical importance. Pseudohyperplastic (Gleason 3) Foamy gland [xanthomatous] (mostly Gleason 3) Hypernephroid (Gleason 4) Atrophic (Gleason 3 or 4) Microcystic (Gleason 3) With Paneth-cell like changes (Gleason 3 or 4) With collagenous micronodules (Gleason 3) With glomeruloid formations (Gleason 3 or 4) With oncocytic changes (Gleason 3 or 4) Table 2. Unusual prostate cancer. Ductal carcinoma (Gleason 4) Mucinous (colloid) carcinoma (mostly Gleason 4 rarely 3) Mucinous signet ring cell carcinoma (no Gleason) Small cell carcinoma (no Gleason) Sarcomatoid carcinoma and (no Gleason) carcinosarcoma Pleomorphic giant cell (Gleason 5) Adenosquamous carcinoma (no Gleason) Squamous carcinoma (no Gleason) Basal cell / adenoid-cystic carcinoma (no Gleason) Lymphoepithelioma- like carcinoma (no Gleason) Urothelial carcinoma involving prostatic (no Gleason) ducts with or without stromal invasion The glands of acinar PC grow in haphazard fashion and are more crowded than normal prostate glands (Fig. 1). PC glands are often situated between benign glands. In dedifferentiated cancer cribriform structures (so called gland in gland ) structures appear or the cancer cells grow intraductally in solid complexes resembling the comedo carcinomas of the mammary gland. Completely undifferentiated PC are composed of sheets of cancer cells or isolated individual cells. A very important cytological feature is the nucleolus which is present with few exceptions in all PC nuclei, but is rarely seen or extremely small in the cells of the normal glands. The architectural pattern of PC are the key components of the Gleason grading system, which completely disregards the cytological features (4). The current Gleason grading system has evolved from its original description, first modified by Gleason and Mellinger in 1974 (5) and most recently in 2005 by the International Society of Urological Pathology (ISUP) (6). The new modification recommends Gleason score 6 as the lowest grade to be assigned on biopsy material. The original Gleason system restricted Gleason pattern 4 to cases with irregular cribriform architecture and fused glands. In the modified system, almost all cribriform patterns were considered Gleason pattern 4 along with poorly formed and fused glands. The Gleason score should include the most and the worst i.e. the architectural component with the largest extension and the most undifferentiated part of the tumor (Gleason grade >3) regardless of the extension of this part. In the original interpretation tumor components accounting for <5% were neglected. Moreover, in the reports Gleason score 7 should be clearly stated as 3+4 or 4+3 according to the amount of tumor, whereby 4+3 has a prognosis very similar to those of Gleason 8 (7). A recent proposal by the Epstein (7) group is to use prognostic groups, which are based on Gleason score (Table 3). Figure 1. Acinar (conventional) carcinoma with haphazardly distributed gland with the typical intraluminal bluish mucin. Table 3. Gleason score can be grouped and range from the most favorable prognostic group I to the least favorable group V (7). Gleason score 6 Gleason score 3+4 = 7 Gleason score 4+3= 7 Gleason score 8 Gleason score 9-10 Prognostic Grade Group I Prognostic Grade Group II Prognostic Grade Group III Prognostic Grade Group IV Prognostic Grade Group V Variants of acinar (conventional) PC Pseudohyperplastic PC Pseudohyperplastic carcinoma first described by Humphrey et al. (8) accounts for 1.5% of PC and is a neoplasm that can be easily mistaken for benign nodular hyperplasia. The histological aspect at low magnification shows well-differentiated mediumsized glands with cystic dilatatioion in a tight arrangement that imports a benign appearance (Fig. 2). Corpora amylacea are found in some cases (8). However, the lining cells show nucleomegaly and promi- 2

Prostate cancer variants nent nuclei in most of the neoplastic glands, and the high-molecular-weight keratin (34BE12) immunostain reveal absence of basal cells and α-methylacylcoaracemase is not always positive (8). Pseudohyperplastic PC is a moderately differentiated and potentially aggressive neoplasm of Gleason grade 3. Atrophic PC Acinar atrophy and postatrophic hyperplasia in the prostate are commonly confused with adenocarcinoma (Fig. 4). The converse situation may also present a diagnostic dilemma some PC mimic atrophy, raising serious concern for the underdiagnosis of malignancy. PC with atrophic features shows a proliferation of malignant acini that architecturally resemble atrophy or postatrophic hyperplasia, yet retain the diagnostic cytologic features of cancer. The acini are round, often dilated and distorted, and lined by flattened attenuated epithelium with scant cytoplasm. All cases had cytologic evidence of malignancy, including nuclear enlargement and prominent nucleoli (12). Figure 2. Pseudohyperplastic prostate cancer which can be easily mistaken for benign nodular hyperplasia. Foamy gland (xanthomatous) PC Foamy gland carcinoma is characterized by abundant xanthomatous cytoplasm and picnotic nuclei (Fig. 3). The typical cytologic features of adenocarcinoma such as nuclear enlargement and prominent nucleoli are frequently absent, which makes this lesion difficult to recognize as carcinoma, especially on biopsy material. The foamy tumor cells are negative for mucin and lipid stains, but positive for colloidal iron and Alcian blue stain. This variant does not appear to harbor a different prognosis compared with usual acinar adenocarcinoma, but diagnostic recognition of foamy gland carcinoma is important because in the majority of cases it is a Gleason grade 4. In some publications the hypernephroid variant is mentioned (11); however, in the literature not one case is described. According to some pictures this type corresponds to a solid variant of a foamy cell PC. Figure 3. The cells of foamy gland carcinoma have xanthomatous cytoplasm and pycnotic nuclei. Figure 4. Atrophic carcinoma with narrow glands and a marked stromal desmoplasia. Microcystic PC Cystic change in adenocarcinoma of the prostate is unusual and may be confused with benign cystic atrophy. The carcinoma glands are cystic dilated with a flat luminal cell lining layer. The mean diameter of the cystic glands is 10-fold greater than adjacent small malignant glands (0.4 0.9 mm) (13). Caveat, microcystic PC is benign-looking at low magnifications! PC with Paneth-cell like changes Paneth-cell like appearance of prostatic adenocarcinoma is considered to be a feature of neuroendocrine differentiation characterized by carcinoma cells with prominent eosinophilic cytoplasmic granules. The round to pyramidal cells are organized in glandular, cribriform, trabecular and patchy isolated structures. Paneth-cell-like carcinoma cells are positive for chromogranin A, synaptophysin, and negative for androgen receptor. In cases with Paneth-cell-like NECs, only the conventional adenocarcinoma component should be assigned a Gleason score. In cases in which the entire tumor is composed of Paneth-celllike cells and areas of the tumor lack glandular dif- 3

Prostate cancer variants ferentiation, the tumors should not be assigned a Gleason score and a comment should be provided as to the generally favorable prognosis of this morphologic pattern of neuroendocrine differentiation (14). PC with collagenous micronodules Collagenous micronodules are microscopic stromal fibrillar aggregates of uncertain histogenesis which arise in association with prostatic adenocarcinoma (Fig. 5). Bostwick et al. (15) identified this structure in 0.6% of needle biopsies and 12.7% of prostatectomies. Figure 5. Collagenous micronodules with stromal fibrillar aggregates. PC with glomeruloid formations Prostatic adenocarcinoma with glomeruloid features is characterized by intraluminal spherical clusters of cancer cells reminiscent of renal glomeruli (Fig. 6). This growth pattern is commonly encountered in highgrade adenocarcinoma. Glomeruloid structures in the prostate represent an uncommon but distinctive pattern of growth that is specific for malignancy and have never been observed in benign or premalignant lesions (16). have round-to-ovoid hyperchromatic nuclei and are strongly positive for PSA. Numerous mitochondria are seen on ultrastructural examination. The metastases of this aggressive variant (mostly Gleason 4) also consist of oncocyts (17). Prostate cancer with unusual histological patterns Ductal carcinoma Prostatic ductal adenocarcinomas account for 1% of prostate cancers and are a variant of adenocarcinoma with unique gross and microscopic features. Historically termed endometrioid because of their nuclear stratification and a postulated origin in the prostatic utricle, it is now accepted that prostatic ductal adenocarcinoma is a variant of adenocarcinoma with unique features. Cystoscopically, these tumors show exuberant polypoid or villous intraurethral projections, grossly mimicking both benign and malignant lesions, such as prostatic urethral polyp and papillary urothelial carcinoma. Thea may cause hematuria, urinary urgency, and eventually urinary retention. Ductal adenocarcinoma may be located centrally around the prostatic urethra or more frequently located peripherally admixed with typical acinar adenocarcinoma. Most commonly, these lesions grow in large cribriform and/or papillary patterns or (Fig. 7), as recently described, in a manner resembling prostatic intraepithelial neoplasia (i.e., 'PIN-like' prostatic ductal adenocarcinoma) (18). Figure 6. Glomeruloid structures in a prostatic carcinoma. PC with oncocytic changes The cancer cells show typical oncocyts - large cells with granular eosinophilic cytoplasm. Tumor cells Figure 7. Prostatic duct carcinoma with papillary pattern resembling endometrial carcinoma. The tumor cells are tall columnar with abundant usually amphophilic cytoplasm, which form a single or pseudostratified layer reminiscent of endometrial carcinoma. The application of the Gleason grading system to ductal carcinoma has proved controversial, with some reports initially advocating not assigning a Gleason score (GS) (19), whereas more recent pu- 4

Prostate cancer variants blications assign scores of 3 (single glands with pseudostratified cells, i.e. PIN-like ), 4 (more complex papillary or cribriform architecture), and 5 (when Comedo-necrosis is present) (19). Most studies have demonstrated that ductal adenocarcinoma is aggressive. Some reported that 25 40% of cases had metastases at the time of diagnosis with a poor 5-year survival rate ranging from 15 to 43% (20). Mucinous (colloid) carcinoma Mucin secretion within nondilated glands is a feature of between 60% and 90% of all PC and may be useful in its detection and diagnosis. In mucinous carcinoma, however, 25% of the resected tumor should be composed of tumor cells/glands floating in extracellular mucin lakes or pools (21). Moreover distended glands filled with mucin (mucinous cysts) may be seen (Fig. 8). Metastatic carcinomas from the colon, bladder, prostatic urethra, or Cowper gland, must be excluded. Grossly, a glistening cut surface may be identified, depending on the extent of colloid features. site for SmCC (24). Unlike SmCC at other sites, prostatic SmCCs seldom manifest clinically evident hormone production (25). Within the neuroendocrine carcinoma component, tumors exhibit a range of morphology, from classic SmCC features as seen in the lung (Fig. 9), that is, diffuse sheets of round blue hyperchromatic cells exhibiting nuclear molding, granular chromatin, inconspicuous nucleoli, scant cytoplasm, and frequent mitoses/apoptotic bodies; to lesions with a large cell neuroendocrine phenotype, including better-defined organoid, palisaded, or trabecular architecture and large cells with abundant cytoplasm and macronucleoli. Diagnostically, SmCC carcinoma should not be assigned a Gleason grade. The outcome for patients with SCC is dismal, with a median survival of 9 17 months (26). Figure 9. Classical oat-cell carcinoma invading the muscular prostate stroma. Figure 8. Mucinous (colloid) carcinoma with carcinoma glands floating in extracellular mucin lakes. In contrast to conventional carcinoma (Fig. 1) the mucin is outside the carcinomatous glands. Mucinous prostate adenocarcinomas behave aggressively (21). Some carcinomas of the prostate will have a signet-ring cell appearance, yet the vacuoles do not contain intracytoplasmic mucin (22). These vacuolated cells may be present as singly invasive cells, in single glands, and in sheets of cells. Only a few cases of prostate cancer have been reported with mucin-positive signet cells (23). Small cell carcinoma Small cell carcinoma (SmCC) of the prostate may be a component of 1% to 5% of all prostatic malignancies and is a relatively common extrapulmonary Sarcomatoid carcinoma and carcinosarcoma There is considerable controversy in the literature regarding nomenclature and histogenesis of these tumors. In some series, carcinosarcoma and sarcomatoid carcinoma are considered separate entities based on the presence of specific mesenchymal elements in the former (27). True carcinosarcomas are composed of a malignant epithelial (carcinomatous) component and a malignant mesenchymal component, whereas sarcomatoid carcinomas are composed of an admixture of both malignant glandular and spindle cell elements which are also of epithelial origin. These cells can show cytokeratin and PSA immunoreactivity (28). Carcinosarcomas are acinar carcinomas combined with a sarcoma component, which consist of undifferentiated spindled and pleomorphic cells arranged in sheets or fascicles. Osteosarcoma and chondrosarcoma are frequently identified. Different types of sarcoma can be found together in the same case. The prognosis is poor (27). 5

Prostate cancer variants Pleomorphic giant cell carcinoma Only few cases have been described to date (29). The tumor is composed of large cells with abundant eosinophilic cytoplasm which sometimes contain multiple nuclei, with or without irregular multilobulations, prominent eosinophilic nucleoli, and marked cytologic atypia. The cells are immunohistochemicaly positive for PSA and AE1/AE3. Squamous and adenosquamous carcinoma These unusual types account for 0.6% of all prostate cancers (30). Pure squamous carcinomas (SqCC) are characterized by infiltrating nests, strands, and sheets of polygonal cells with nuclear atypia, with squamous differentiation manifested as individual cell keratinization, intercellular bridges, and/or keratin pearl formation (Fig. 10). Adenosquamous carcinonoma (ASC) is defined by the presence of both glandular (acinar) and SqCC components (31). Direct transition from glandular to squamous epithelium can be seen (Fig. 11). About half of ASC arise after endocrine therapy or radiotherapy of a conventional PC (31). The mean survival for prostatic SqCC is not long, at 6 24 months (32). Basal cell and adenoid-cystic carcinoma This tumor has been classified, in accordance with the prevalent pattern of growth, as adenoid-cystic carcinoma or basaloid cell carcinoma (BCC), with the former growth pattern being considered the main feature of this entity (33). The pure BCC, showing islands and cords of epithelial cells with peripheral palisading like in "basalioma" of the skin (Fig. 12), characterize the first type, morphologically similar to basal cell carcinoma of the skin. The adenoidcystic carcinoma is composed of infiltrating basaloid cells forming dilated acinar and cribriform spaces with luminal basement membrane-like material (34). Focal squamous differentiation and clear cell appearance can be seen in both types. The basal cells are positive for high molecular cytokeratin and p63. These tumors predominantly manifest local infiltrative behavior. A small percentage behaves aggressively with local recurrences and distant metastases. The most common morphology among those with aggressive behavior is large solid nests, frequently with central necrosis, high Ki67%, and less staining with basal cell markers (33). Figure 10. Squamous cell carcinoma with calcified keratin masses. Figure 11. Adenosquamous carcinoma with direct transition from glandular to squamous epithelium. Figure 12. Basal cell carcinoma with cords and islands of tumor cells with peripheral palisading like in skin basalioma. Lymphoepithelioma-like PC This is a rare type of prostate cancer with some 10 cases reported. The tumor is characterized by a malignant epithelial component densely infiltrated by lymphoid cells. All described cases were associated with conventional adenocarcinoma. The lymphoepithelioma-like carcinoma component is characterized by indistinct cytoplasmic borders and a syncytial growth pattern. The stroma is densely infiltrated by lymphoid cells admixed with some plasma cells and neutrophils. Staining demonstrated that lymphoepithelioma-like carcinomas are immunohistochemically positive for PSA and racemase. The be- 6