title: Chromophobe renal cell carcinoma with neuroendocrine and neuroendocrine-like features. Morphologic, immunohistochemical, ultrastructural, and array comparative genomic hybridization analysis of 18 cases and review of the literature.
abstract: Chromophobe renal cell carcinoma (CRCC) with neuroendocrine differentiation (CRCCND) has only recently been described. Eighteen cases of CRCC with morphologic features suggestive of neuroendocrine differentiation were selected from among 624 CRCCs in our registry. The tissues were fixed in neutral formalin, embedded in paraffin, cut into 4- to 5-μm-thick sections, and stained with hematoxylin and eosin. As CRCC with neuroendocrine features, tumors with following morphology were suggested: (1) trabecular/palisading/ribbon-like, gyriform, insular, glandular, and solid pattern; (2) uniform polygonal cells formed in small islets; and (3) cribriform pattern in combination with palisading. Selected cases were further analyzed using immunohistochemistry, electron microscopy, array comparative genomic hybridization, and fluorescence in situ hybridization. Cases were classified as CRCCND or CRCC with neuroendocrine-like features (CRCCND-L) based on the immunohistochemical expression of neuroendocrine markers: CRCCND, 4 cases, age range 49 to 79 years, size ranged from 2.2 to 22 cm, and CRCCND-L, 14 cases, age range 34 to 74 years, size range 3.8 to 16.5 cm. Follow-up information was available for 11 of 18 patients aged 0.5 to 12 years. Two of 4 CRCCNDs showed aggressive clinical course with metastatic spreading. Chromophobe renal cell carcinomas with neuroendocrine differentiation were focally positive for CD56 (4/4), synaptophysin (4/4), chromogranin A (1/4), and neuron-specific enolase (3/4). All 14 CRCCND-Ls were mostly negative or very weakly focally positive for some of the aforementioned markers. All 18 tumors were positive for cytokeratin 7 and CD117. Ultrastructural analysis showed poorly preserved neuroendocrine granules only in 2 of 4 analyzed CRCCNDs. Losses of chromosomes 1, 2, 6, and 10 were found in all analyzable CRCCNDs, whereas multiple losses (chromosomes 1, 2, 6, 10, 13, 17, and 21) and gains (chromosomes 4, 11, 12, 14, 15, 16, 19, and 20) were found in CRCCND-L.
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Peckova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Martinek
authors.affiliation: Department of Diagnostic Pathology, Kansai Medical University, Hirakata Hospital, Osaka, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Ohe
authors.affiliation: Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.affiliation: Department of Pathology, University Hospital Dubrava, Zagreb, Croatia.
authors.forename: Stela
authors.initials: S
authors.lastname: Bulimbasic
authors.affiliation: Department of Pathology, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Condom Mundo
authors.affiliation: Department of Pathology, Instituto Nacional de Cancerologia, Mexico City, Mexico.
authors.forename: Delia
authors.initials: D
authors.lastname: Perez Montiel
authors.affiliation: Department of Pathology, Cruces University Hospital, Barakaldo, Spain.
authors.forename: Jose I
authors.initials: JI
authors.lastname: Lopez
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Daum
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Rotterova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Bohuslava
authors.initials: B
authors.lastname: Kokoskova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dubova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Pivovarcikova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bauleth
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Grossmann
authors.affiliation: Department of Urology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.affiliation: Department of Urology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Kalusova
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS.
authors.forename: Whitney
authors.initials: W
authors.lastname: Davidson
authors.affiliation: Department of Otorhinolaryngology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Slouka
authors.affiliation: Bioptical Laboratory Chomutov, Chomutov, Czech Republic.
authors.forename: Sulc
authors.initials: S
authors.lastname: Miroslav
authors.affiliation: Department of Pathology, University Hospital Ostrava, Ostrava, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Buzrla
authors.affiliation: Department of Radiology, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Mirka
authors.initials: M
authors.lastname: Hynek
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic; Biomedical Centre, Charles University, Medical Faculty and Charles University Hospital Plzen, Plzen, Czech Republic. Electronic address: hes@medima.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
keywords: Chromophobe renal cell carcinoma; Chromosomal numerical aberrations; Immunohistochemistry; Kidney; Neuroendocrine differentiation; aCGH