title: Morphological, immunohistochemical, and chromosomal analysis of multicystic chromophobe renal cell carcinoma, an architecturally unusual challenging variant.
abstract: Chromophobe renal cell carcinoma (ChRCC) is typically composed of large leaf-like cells and smaller eosinophilic cells arranged in a solid-alveolar pattern. Eosinophilic, adenomatoid/pigmented, or neuroendocrine variants have also been described. We collected 10 cases of ChRCC with a distinct multicystic pattern out of 733 ChRCCs from our registry, and subsequently analyzed these by morphology, immunohistochemistry, and array comparative genomic hybridization. Of the 10 patients, 6 were males with an age range of 50-89 years (mean 68, median 69). Tumor size ranged between 1.2 and 20 cm (mean 5.32, median 3). Clinical follow-up was available for seven patients, ranging 1-19 years (mean 7.2, median 2.5). No aggressive behavior was documented. We observed two growth patterns, which were similar in all tumors: (1) variable-sized cysts, resembling multilocular cystic neoplasm of low malignant potential and (2) compressed cystic and tubular pattern with slit-like spaces. Raisinoid nuclei were consistently present while necrosis was absent in all cases. Half of the cases showed eosinophilic/oncocytic cytology, deposits of pigment (lipochrome) and microcalcifications. The other half was composed of pale or mixed cell populations. Immunostains for epithelial membrane antigen (EMA), CK7, OSCAR, CD117, parvalbumin, MIA, and Pax 8 were positive in all tumors while negative for vimentin, TFE3, CANH 9, HMB45, cathepsin K, and AMACR. Ki67 immunostain was positive in up to 1 % of neoplastic cells. Molecular genetic examination revealed multiple chromosomal losses in two fifths analyzable tumors, while three cases showed no chromosomal numerical aberrations. ChRCC are rarely arranged in a prominent multicystic pattern, which is probably an extreme form of the microcystic adenomatoid pigmented variant of ChRCC. The spectrum of tumors entering the differential diagnosis of ChRCC is quite different from that of conventional ChRCC. The immunophenotype of ChRCC is identical with that of conventional ChRCC. Chromosomal numerical aberration pattern was variable; no chromosomal numerical aberrations were found in three cases. All the cases in this series have shown an indolent and non-aggressive behavior.
authors.affiliation: Department of Pathology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|Department of Pathology and Experimental Therapeutics, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Maria Pané
authors.initials: MP
authors.lastname: Foix
authors.affiliation: Department of Pathology, University of Split, Split, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Dunatov
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Martinek
authors.affiliation: Department of Pathology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|Department of Pathology and Experimental Therapeutics, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Enric Condom
authors.initials: EC
authors.lastname: Mundó
authors.affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Saul
authors.initials: S
authors.lastname: Suster
authors.affiliation: Department of Pathology, East University, Riga, Latvia.
authors.forename: Maris
authors.initials: M
authors.lastname: Sperga
authors.affiliation: Department of Pathology, Cruces University Hospital, Biocruces Research Institute, University of the Basque Country, Barakaldo, Spain.
authors.forename: Jose I
authors.initials: JI
authors.lastname: Lopez
authors.affiliation: "Ljudevit Jurak" Pathology Department, Clinical Hospital Center "Sestre milosrdnice", Zagreb, Croatia.
authors.forename: Monika
authors.initials: M
authors.lastname: Ulamec
authors.affiliation: Department of Pathology, Clinical Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Stela
authors.initials: S
authors.lastname: Bulimbasic
authors.affiliation: Department of Pathology, Instituto Nacional de Cancerologia, Mexico City, Mexico.
authors.forename: Delia Perez
authors.initials: DP
authors.lastname: Montiel
authors.affiliation: Department of Pathology, Faculty of Medicine, Royal Columbian Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Alaghehbandan
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Peckova
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Krystina
authors.initials: K
authors.lastname: Pivovarcikova
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Daum
authors.initials: D
authors.lastname: Ondrej
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Rotterova
authors.affiliation: Department of Pathology, Clinical Center of the University of Srajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Faruk
authors.initials: F
authors.lastname: Skenderi
authors.affiliation: Department of Urology, Medical Faculty and Charles University Hospital, Charles University, Plzen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Prochazkova
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Dusek
authors.affiliation: Department of Urology, Medical Faculty and Charles University Hospital, Charles University, Plzen, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.affiliation: Department of Pathology, , Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic. hes@medima.cz.|Biomedical Centre, Faculty of Medicine in Lzen, Charles University in Prague, Plzen, Czech Republic. hes@medima.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
mesh_terms: D018249:Adenoma, Oxyphilic / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1
keywords: ArrayCGH; Chromophobe renal cell carcinoma; Immunohistochemistry; Kidney; Multicystic