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1.
Virchows Arch ; 479(1): 57-67, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33447899

RESUMEN

Clear cytoplasm is a major characteristic feature of most malignant renal neoplasms. Benign clear cells in the renal parenchyma, usually histiocytes, can occasionally be found, but they are infrequently of an epithelial nature. We report histological, immunohistochemical, ultrastructural, and cytogenomic features of clear epithelial cell clusters incidentally found in four kidney specimens. Multiple microscopic clear cell clusters were present in the cortex, often in subcapsular location. They were composed of large epithelial cells with strikingly clear cytoplasm, without nuclear atypia, arranged in solid nests, and some tubules with narrow lumina. Immunohistochemically, they were positive for AE1AE3, PAX 8, EMA, kidney-specific cadherin, cytokeratin 7, E cadherin, and CD117, with focal immunoreactivity for CD10. Carbonic anhydrase IX, vimentin, and markers related to apoptosis and proliferation were negative. Ultrastructurally, the cytoplasms were enlarged and poor in organelles, showing ballooning degeneration. Array comparative genomic hybridization showed no chromosomal gains or losses. Clear cell clusters constitute a rare finding in the kidney and must be differentiated from benign lesions (ectopic adrenal tissue, osmotic tubulopathy, histiocytic clusters, renal adenomas) and renal cell carcinomas. Clear cell clusters appear to be generated from "endocrine-type" atrophic tubules whose cells are enlarged due to intracellular oedema. Immunohistochemistry shows a distal nephron phenotype with a limited expression of a proximal marker, CD10. Coexisting chronic renal disease or ischemic conditions seem to be related to the development of clear cell clusters. Pathological, ultrastructural, and cytogenomic features do not support a preneoplastic nature of this lesion, at least in the cases studied here.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Riñón/patología , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Carcinoma de Células Renales/química , Carcinoma de Células Renales/ultraestructura , Hibridación Genómica Comparativa , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Humanos , Inmunohistoquímica , Riñón/química , Riñón/ultraestructura , Neoplasias Renales/química , Neoplasias Renales/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas
2.
Med Oncol ; 37(4): 28, 2020 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-32172294

RESUMEN

Renal cell carcinoma is a lethal disease that is often discovered incidentally. New non-invasive biomarkers are needed to aid diagnosis and treatment. Extracellular vesicles (EVs), membranous vesicles secreted by all cells, are a promising potential source for cancer biomarkers, but new methods are required that are both sensitive and specific for cancer identification. We have developed an EV isolation protocol optimized for kidney tumor and normal kidney tissue that yields a high vesicle concentration, confirmed by nanoparticle tracking analysis (NanoSight) and by nanoscale flow cytometry (NanoFCM). Using Western blot, we confirmed presence of EV markers CD81, CD63, flotillin-1, and absence of cellular debris, calnexin. Transmission electron microscopy images demonstrate intact membranous EVs. This new method improves existing protocols with additional steps to reduce contaminants in the EV product. Characterization of our isolation product confirms successful isolation of EVs with minimal contamination. The particle yields of our protocol are consistent and high as assessed by both standard and novel methods. This optimized protocol will contribute to biomarker discovery and biological studies of EVs in renal cancer.


Asunto(s)
Carcinoma de Células Renales/ultraestructura , Vesículas Extracelulares , Neoplasias Renales/ultraestructura , Biomarcadores/metabolismo , Carcinoma de Células Renales/patología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/ultraestructura , Femenino , Citometría de Flujo , Humanos , Riñón/patología , Riñón/ultraestructura , Neoplasias Renales/patología , Células MCF-7 , Masculino , Microscopía Electrónica de Transmisión , Nanopartículas/metabolismo , Reproducibilidad de los Resultados , Flujo de Trabajo
3.
Rev Esp Patol ; 52(1): 57-61, 2019.
Artículo en Español | MEDLINE | ID: mdl-30583834

RESUMEN

Tubulocystic renal carcinoma is an uncommon neoplasm. We present a case of a patient presenting with multiple renal colic. A nodular cystic lesion was an incidental sonographic finding which increased in size during subsequent follow-ups. The patient underwent radical nephrectomy and tubular renal carcinoma was diagnosed histopathologically and immunohistochemically.


Asunto(s)
Carcinoma de Células Renales/ultraestructura , Neoplasias Renales/ultraestructura , Adulto , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/diagnóstico por imagen , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico por imagen , Masculino , Cólico Renal/etiología , Tomografía Computarizada por Rayos X , Ultrasonografía
4.
Ultrastruct Pathol ; 42(5): 458-463, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30252563

RESUMEN

A multiple myeloma patient, who had been treated with a hematopoietic stem cell transplant, underwent a renal biopsy for investigation of a possible relapse of disease as indicated by increased serum creatinine and positive urinary Bence-Jones protein containing increased kappa light chain. Paraprotein-related renal disease was not evident by light microscopy or immunofluorescence microscopy however electron microscopy demonstrated a proximal tubulopathy with intracytoplasmic non-crystalline inclusions. The ultrastructural findings suggested possible end-organ involvement by the disease and follow-up studies subsequently revealed a relapsed multiple myeloma in the patient. The case exemplifies the usefulness of electron microscopy in detecting paraproteins that, in some instances, may be difficult to demonstrate by other techniques.


Asunto(s)
Túbulos Renales Proximales/ultraestructura , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/ultraestructura , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/ultraestructura , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/ultraestructura , Túbulos Renales Proximales/patología , Microscopía Electrónica de Transmisión , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/patología
5.
BMJ Case Rep ; 20172017 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-29066638

RESUMEN

Birt-Hogg-Dubé (BHD) is a rare syndrome of inherited renal cell carcinomas, characterised by cutaneous lesions and pulmonary cysts and pneumothorax in a vast majority of the patients. Awareness of this syndrome is important in order to refer patients for genetic counselling and personalised follow-up as soon as possible. We describe a case of a 30-year-old female referred to our institution due to incidental discovery of solid bilateral renal masses. Renal biopsies were consistent with chromophobe tumour, and bilateral nephrectomy was performed. Gross examination revealed deformed kidneys with 28 brown and solid lesions, size variable between 0.1 and 6 cm, histologically corresponding to renal cell carcinomas, chromophobe type. Genetic test was required that showed a c.573delGAinsT frameshift mutation in heterozigosity at the folliculin gene, consistent with BHD diagnosis.


Asunto(s)
Síndrome de Birt-Hogg-Dubé/complicaciones , Síndrome de Birt-Hogg-Dubé/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico por imagen , Adulto , Concienciación , Dolor de Espalda/diagnóstico , Dolor de Espalda/etiología , Síndrome de Birt-Hogg-Dubé/patología , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/ultraestructura , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/ultraestructura , Nefrectomía/métodos , Neumotórax/diagnóstico , Neumotórax/etiología , Proteínas Proto-Oncogénicas/genética , Enfermedades Raras , Enfermedades de la Piel/patología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Proteínas Supresoras de Tumor/genética , Ultrasonografía
6.
Br J Cancer ; 117(5): 752-755, 2017 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-28742796

RESUMEN

BACKGROUND: Leukocyte telomere length (LTL) is a potential biomarker of cancer prognosis; however, evidence for renal cell carcinoma (RCC) is inconsistent. METHODS: We investigated LTL and RCC-specific survival among 684 cases from the US kidney cancer study (USKC) and 241 cases from the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO). Leukocyte telomere length was measured by quantitative polymerase chain reaction, and hazard ratios (HRs) and 95% confidence intervals (CIs) computed using multivariable Cox models. RESULTS: Short LTL was associated with poorer disease-specific survival in both USKC (lowest vs highest quartile: HR: 2.3, 95% CI: 1.2-4.4; P for trend=0.02) and PLCO (HR: 2.4, 95% CI: 1.0-5.4; P=0.04). Among USKC cases, the association was strongest for stage-I RCC (HR: 5.5, 95% CI: 1.6-19.0; P=0.006). CONCLUSIONS: Our findings suggest that shorter LTL is an independent marker of poor RCC prognosis, particularly for stage-I disease.


Asunto(s)
Carcinoma de Células Renales/ultraestructura , Neoplasias Colorrectales/ultraestructura , Neoplasias Renales/ultraestructura , Leucocitos/ultraestructura , Neoplasias Pulmonares/ultraestructura , Neoplasias Ováricas/ultraestructura , Neoplasias de la Próstata/ultraestructura , Acortamiento del Telómero , Telómero/ultraestructura , Anciano , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Estudios de Casos y Controles , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Neoplasias Renales/sangre , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/sangre , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Pronóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Tasa de Supervivencia
7.
Am J Surg Pathol ; 41(5): 663-676, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28288037

RESUMEN

Xp11 translocation renal cell carcinomas (RCC) are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathologic manifestations. Only 3 RBM10-TFE3 RCCs have been reported to date. Here, we added 4 cases of this rare type of tumors with clinicopathologic, immunohistochemical, molecular, and ultrastructural analyses. Most tumors had similar patterns with mixed architectures as follows: acinar, tubular and papillary patterns of epithelioid cells combined with sheets of small cells with "pseudorosette-like" architectures, mimicking the typical morphology of t(6;11) RCC. Cytoplasmic vacuolization, nuclear groove, and psammoma bodies were observed in most cases. Immunohistochemically, all 4 cases demonstrated moderate to strong immunoreactivity for TFE3, Cathepsin K, CD10, Ksp-cadherin, E-cadherin, P504S, RCC marker, PAX8 and vimentin, whereas negativity for TFEB, HMB45, and CK7. CKpan and Melan-A were at least focally expressed. The antibody to Ki-67 showed labeling of 3% to 8% (mean, 5%) of tumor cell nuclei. ;Of interest, several immunostainings demonstrated expression discrepancy in different histology patterns. RBM10-TFE3 fusion transcripts were identified in all cases by reverse transcription-polymerase chain reaction. By fluorescence in situ hybridization, all 4 cases showed unusual split signals with a distance <1 signal diameter (co-localized or subtle split signals) and usually had false-negative results. We also observed ultrastructures, including melanin pigment, nuclear groove, numerous glycogens, mitochondrion with areas of high electron density material, basement membrane material, and cell junctions with poor development. All 4 patients were alive with no evidence of recurrent disease. Our report adds to the known data regarding RBM10-TFE3 RCC.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor , Carcinoma de Células Renales/genética , Inversión Cromosómica , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 6 , Cromosomas Humanos X , Fusión Génica , Neoplasias Renales/genética , Melaninas/análisis , Proteínas de Unión al ARN/genética , Translocación Genética , Anciano , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/química , Carcinoma de Células Renales/ultraestructura , Catepsina K/análisis , China , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Renales/química , Neoplasias Renales/ultraestructura , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
J Biomol Struct Dyn ; 35(5): 1020-1029, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26982119

RESUMEN

In our study, renal cancer is induced in rats making use of dimethylnitrosamine (DMN). G1 - Group 1 were control rats and G2 - Group 2 rats were given a single intra-peritoneal injection of DMN of 50 mg/kg body weight resulting in 100% incidences of renal tumors after 12 months. SEM and histopathology confirmed the presence of renal cancer in the DMN-treated rats. Making use of ammonium sulfate precipitation and gel filtration chromatography on Sephacryl S-100HR column, a thiol protease inhibitor was isolated from kidney of control rats known as Rat kidney Cystatin (RKC) as well as from kidney of cancerous rat called as Cancerous Rat Kidney Cystatin (CRKC). Both these inhibitors were characterized, and interestingly, it was found that CRKC showed greater anti-papain activity and also it was stable in a broad pH and temperature range thus implying that CRKC is more stable as compared to RKC. UV and fluorescence spectroscopy point out in structural difference between RKC and CRKC which was further confirmed by Circular dichroism (CD) and FTIR spectroscopy. Our study clearly showed that kidney cystatin is structurally modified in the case of renal cancer and performs its role in a more efficacious manner.


Asunto(s)
Cistatinas/química , Animales , Biomarcadores de Tumor , Biopsia , Dicroismo Circular , Cistatinas/metabolismo , Dimetilnitrosamina/efectos adversos , Concentración de Iones de Hidrógeno , Neoplasias Renales/inducido químicamente , Neoplasias Renales/diagnóstico , Neoplasias Renales/metabolismo , Neoplasias Renales/ultraestructura , Masculino , Pronóstico , Estabilidad Proteica , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Termodinámica
9.
Int J Mol Sci ; 17(11)2016 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-27827846

RESUMEN

The renal microvasculature is targeted during aging, sometimes producing chronic kidney disease (CKD). Overdiagnosis of CKD in older persons is concerning. To prevent it, a new concept of "healthy aging" is arising from a healthy renal donor study. We investigated the renal microcirculatory changes of three older persons and compared them with that of one patient with nephrosclerosis using a three-dimensional (3D) reconstruction technique that we previously developed. This method uses a virtual slide system and paraffin-embedded serial sections of surgical material that was double-immunostained by anti-CD34 and anti-α smooth muscle actin (SMA) antibodies for detecting endothelial cells and medial smooth muscle cells, respectively. In all cases, the 3D images proved that arteriosclerotic changes in large proximal interlobular arteries did not directly induce distal arterial change or glomerulosclerosis. The nephrosclerotic patient showed severe hyalinosis with luminal narrowing of small arteries directly inducing glomerulosclerosis. We also visualized an atubular glomerulus and intraglomerular dilatation of an afferent arteriole during healthy aging on the 3D image and showed that microcirculatory changes were responsible for them. Thus, we successfully visualized healthy aged kidneys on 3D images and confirmed the underlying pathology. This method has the ability to investigate renal microcirculatory damage during healthy aging.


Asunto(s)
Adenocarcinoma de Células Claras/diagnóstico por imagen , Envejecimiento/patología , Carcinoma de Células Renales/diagnóstico por imagen , Imagenología Tridimensional/métodos , Glomérulos Renales/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Microvasos/diagnóstico por imagen , Nefroesclerosis/diagnóstico por imagen , Actinas/genética , Actinas/metabolismo , Adenocarcinoma de Células Claras/irrigación sanguínea , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/ultraestructura , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Antígenos CD34/genética , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/ultraestructura , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Expresión Génica , Humanos , Glomérulos Renales/irrigación sanguínea , Glomérulos Renales/ultraestructura , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/metabolismo , Neoplasias Renales/ultraestructura , Masculino , Microtomía , Microvasos/metabolismo , Microvasos/ultraestructura , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/ultraestructura , Nefroesclerosis/metabolismo , Nefroesclerosis/patología , Adhesión del Tejido
10.
Med Mol Morphol ; 49(1): 57-61, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26508100

RESUMEN

In a case of metanephric adenoma of the kidney, many apical cytoplasmic blebs were found on the luminal surface of tumor cells. The tumor, measuring 15 mm in diameter, was found incidentally in the right kidney of a 40-year-old woman. It consisted of a dense proliferation of cuboidal cells forming small tubules of round or irregular shape. The apical portion of the cytoplasm of tumor cells exhibited club-shaped expansion or dome-like protrusion which was largely occupied by numerous free ribosomes. The neck portion of the protruded apical cytoplasm was constricted, and the apical cytoplasm appeared to have been "pinched-off" and shed into the lumen. The prominent formation of apical cytoplasmic blebs has, to our knowledge, not been documented in renal tumors except in angiomyoadenomatous tumors. Its pathological significance is unknown, but it most likely represents a response of tumor cells to some hypoxic or toxic cellular injuries.


Asunto(s)
Adenoma/patología , Citoplasma/patología , Neoplasias Renales/patología , Adenoma/terapia , Adenoma/ultraestructura , Adulto , Femenino , Humanos , Neoplasias Renales/terapia , Neoplasias Renales/ultraestructura
11.
Pol J Pathol ; 66(1): 3-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26017874

RESUMEN

Rhabdoid morphology in renal cell carcinoma (RCC) may, like sarcomatoid change, be perceived as a type of dedifferentiation, and is a poor prognostic factor. Histologically, rhabdoid neoplastic cells are round to polygonal cells with globular eosinophilic cytoplasmic inclusions and eccentric vesicular nuclei and enlarged nucleoli. All types of RCC, including clear cell, papillary, chromophobe, collecting duct carcinoma, renal medullary carcinoma, acquired cystic disease-associated RCC, ALK-positive renal cancer and unclassified RCC, may display a variably prominent rhabdoid phenotype. Immunohistochemically, the cytoplasm of rhabdoid cells shows positivity for vimentin and/or cytokeratin. Ultrastructurally, cytoplasmic whorls/aggregates of intermediate filaments correspond to light microscopically observed inclusions. Genetically, a previous report suggests that combined loss of BAP1 and PBRM1 may be associated with rhabdoid morphology. As with sarcomatoid change, pathologists should describe, estimate and state the proportion of tumor cells with a rhabdoid phenotype in the routine pathology report of RCC.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Tumor Rabdoide/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Carcinoma de Células Renales/química , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/ultraestructura , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Neoplasias Renales/química , Neoplasias Renales/genética , Neoplasias Renales/terapia , Neoplasias Renales/ultraestructura , Técnicas de Diagnóstico Molecular , Valor Predictivo de las Pruebas , Pronóstico , Tumor Rabdoide/química , Tumor Rabdoide/genética , Tumor Rabdoide/terapia , Tumor Rabdoide/ultraestructura
12.
Acta Histochem ; 117(6): 505-11, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25935740

RESUMEN

The small cell variant renal oncocytoma is until now a rarely described and easily misdiagnosed subtype of renal oncocytoma. The tissue morphology, immunohistochemical profile, ultrastructural and molecular characteristics of four cases of small cell variant renal oncocytoma were analyzed and the literature was reviewed. The patients were three women and one man with ages ranging from 51 to 76 years. The size of the tumors ranged from 3 to 8.5 cm in diameter. The follow-up duration ranged from 6 to 58 months. All patients lived uneventfully without tumor recurrence or metastasis. The tumors were grayish yellow to brown, well demarcated, with a central scar or cystic change. Microscopically, the tumor was arranged in lobular structure containing dense small acini or tubular structures, with small cells featuring weak eosinophilic and scant cytoplasm, small round nuclei and inconspicuous nucleoli. No mitotic figures or necrosis were discerned. The immunohistochemical profile of small cell variant of renal oncocytoma is partially consistent with classic oncocytoma, expressing EMA, CK18, CD117 and E-cad. However, MITO and S-100A1 were intensively expressed in classic RO, but neither of them was expressed in small cell variant RO. Ultrastructurally, a small number of organelles was revealed in the tumor cell, including a few mitochondria, lysosomes and microvilli, less than those in the classic oncocytoma. No genetic aberrations were found in all cases regardless of clinicopathological characteristics and tissue types. Small cell variant renal oncocytoma of the kidney is frequently difficult to be differentiated from other benign and malignant small cell tumors with eosinophilic cytoplasm. The immunohistochemical profile, ultrastructural and genetic features of the tumor are integrally presented here for the first time. Acquaintance with the special characteristics of the tumor could facilitate the correct diagnosis of the tumor.


Asunto(s)
Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/ultraestructura , Neoplasias Renales/diagnóstico , Neoplasias Renales/ultraestructura , Anciano , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Masculino , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Persona de Mediana Edad
13.
Cell Death Dis ; 6: e1585, 2015 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-25569102

RESUMEN

Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-producing metabolic pathways. One exception seems to be the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most other pathways than that of glycolysis has been shown to be reduced. This makes ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of the disease. However, few studies have so far addressed this issue. In this report, we show a strikingly reduced mitochondrial respiratory capacity of primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in established ccRCC cell lines, a finding that highlights the importance of using biologically relevant models in the search for new candidate cancer therapies. 3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been shown to be well tolerated in vivo, should be further analyzed for the possible development of selective treatment strategies for patients with ccRCC.


Asunto(s)
Carcinoma de Células Renales/patología , Glucólisis/efectos de los fármacos , Neoplasias Renales/patología , Mitocondrias/metabolismo , Piruvatos/farmacología , Adenosina Trifosfato/biosíntesis , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/ultraestructura , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Respiración de la Célula/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Renales/genética , Neoplasias Renales/ultraestructura , Lactatos/metabolismo , Mitocondrias/efectos de los fármacos , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Simportadores/genética , Simportadores/metabolismo
14.
Pathol Res Pract ; 210(7): 454-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24702883

RESUMEN

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor with relatively indolent behavior. Non-classic morphological variants have not been well studied and rarely been reported. We report a challenging case MTSCC with a peculiar morphology in a 42-year-old man, arising in a background of end-stage renal disease (ESRD). Predominant areas with extensive papillary architecture, psammoma bodies and stromal macrophageal aggregates, reminiscent of a papillary renal cell carcinoma (papillary RCC), were intermixed with foci that transitioned into a MTSCC-like morphology exhibiting elongated tubules and a low grade spindle cell component in a background of mucinous stroma. Immunohistochemistry demonstrated diffuse positivity for P504s/AMACR and vimentin in tumor cells. Focal positivity for RCC, CD10 and CK7 was also noted. Kidney-specific cadherin, cytokeratin 34betaE12 and TFE3 stains were negative in the tumor. The major differential diagnostic considerations were papillary RCC, clear cell papillary RCC, and Xp11.2 translocation carcinoma. Negative FISH studies for trisomy 7 and 17 in both papillary and spindled components supported the diagnosis of MTSCC. The ultrastructural profile was not entirely indicative of the cellular origin of the tumor. Cytogenetic analysis should be performed in atypical cases of MTSCC for precise diagnosis.


Asunto(s)
Adenocarcinoma Mucinoso/ultraestructura , Biomarcadores de Tumor/análisis , Carcinoma/ultraestructura , Neoplasias Renales/ultraestructura , Adenocarcinoma Mucinoso/genética , Adulto , Carcinoma/genética , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Renales/genética , Trasplante de Riñón , Masculino , Microscopía Electrónica de Transmisión
15.
JBR-BTR ; 97(5): 298-300, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25597212

RESUMEN

Solitary fibrous tumor (SFT) is an unusual spindle cell neoplasm rarely described in the kidney. Usually occurring in the pleura, it has also been described in various extrapleural sites. We report a rare case of SFT of the kidney fortuitously found in a 55-year-old patient. The imaging features are illustrated. The definite diagnosis was made through histological and immunohistochemical study after radical nephrectomy.


Asunto(s)
Neoplasias Renales/diagnóstico , Neoplasias Renales/cirugía , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/cirugía , Medios de Contraste , Diagnóstico Diferencial , Humanos , Riñón/diagnóstico por imagen , Riñón/cirugía , Neoplasias Renales/ultraestructura , Persona de Mediana Edad , Tomografía Computarizada Multidetector/métodos , Nefrectomía/métodos , Intensificación de Imagen Radiográfica/métodos , Tumores Fibrosos Solitarios/ultraestructura , Ultrasonografía Doppler/métodos
16.
Zhonghua Bing Li Xue Za Zhi ; 43(11): 728-31, 2014 Nov.
Artículo en Chino | MEDLINE | ID: mdl-25582249

RESUMEN

OBJECTIVE: To study the clinicopathological features, differential diagnosis and prognosis of clear cell papillary renal cell carcinoma (CCPRCC). METHODS: The histological, immunohistochemical, and molecular features were studied in 11 cases and follow-up data were also analyzed. RESULTS: There were a total of 3 females and 8 males. The age of patients were ranged from 33 to 72 years(mean age 52.5 years). The diameters of tumors varied from 1cm to 4 cm. Histologically, papillary and cystic architecture were present at least focally in all tumors. The papillae were covered by small to medium-sized cuboidal cells with abundant clear cytoplasm and often showed extensive secondary branching, which were often folded and densely packed, resulting in a solid appearance. The nuclei were round and uniform in shape; nucleoli were not prominent (Fuhrman grade 1 or 2). Neither mitotic figures nor necrosis was present. All 11 cases exhibited moderate to strong positivity for CK7, CA9, vimentin, and HIF-1α, coupled with negative reactions for CD10, P504S, and TFE3. Ksp-cadherin was positively expressed in 8 cases.VHL gene mutations were not found in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. CONCLUSIONS: CCPRCC is uncommon and seemed to be an indolent tumor. The differential diagnosis should be included tumors, which harbor clear cell and papillary structure including clear cell renal cell carcinoma, papillary renal cell carcinoma, Xp11 translocation renal cell carcinoma, and CCPRCC. Immunohistochemical and molecular analysis may be help for its diagnosis.


Asunto(s)
Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Adulto , Anciano , Carcinoma de Células Renales/química , Carcinoma de Células Renales/ultraestructura , Cromosomas Humanos Par 3 , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Neoplasias Renales/química , Neoplasias Renales/ultraestructura , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Racemasas y Epimerasas/análisis , Translocación Genética , Carga Tumoral
17.
Int J Clin Exp Pathol ; 6(12): 2936-42, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24294381

RESUMEN

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal neoplasm, which was initially described in end-stage renal disease (ESRD), but some cases have been reported in otherwise normal kidneys. We report a series of 11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was available for 8 patients. No patients developed local recurrence, distant or lymph-node metastasis, or cancer death. Histologically, all tumors exhibit morphologic features typical of CCPRCC including a mixture of cystic and papillary components, covered by small to medium-sized cuboidal cells with abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity for CK7, CA9, Vim, and HIF-1α, coupled with negative reactions for CD10, P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. Ultrastructurally, the tumor cells composed of numerous glycogens with scanty cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome 3) was detected in 3 cases suggesting that at least some of these lesions have demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed of numerous glycogens with scanty cell organelles, reminiscent of CCRCC suggesting the close pathogenesis relationship of CCPRCC with CCRCC.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/ultraestructura , Neoplasias Renales/genética , Neoplasias Renales/ultraestructura , Adulto , Anciano , Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Anhidrasa Carbónica IX , Anhidrasas Carbónicas/análisis , Carcinoma de Células Renales/química , Carcinoma de Células Renales/cirugía , Deleción Cromosómica , Cromosomas Humanos Par 3 , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Renales/química , Neoplasias Renales/cirugía , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Mutación , Nefrectomía , Fenotipo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética
20.
Virchows Arch ; 462(5): 575-81, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23525677

RESUMEN

Tubulocystic carcinoma of the kidney (TCCK) is a tumor entity, which is not yet included in the WHO classification of renal tumors. The histogenesis of this neoplasm is uncertain. This study was undertaken to determine (1) the incidence of TCCK and (2) immunohistochemical and ultrastructural characteristics of those tumors that qualify as TCCK by the current definitions. From January 1, 2003 to December 31, 2012, a total of 615 renal cell carcinomas (RCCs) were seen by the Department of Pathology, University of Maryland Medical Center. Four TCCKs were identified (4/615, <1 %). TCCK is a distinctive group of kidney tumors with a male predominance and noteworthy macroscopic spongy appearance. Microscopically, the tumors were composed of tubules and cysts lined by a single layer of eosinophilic, columnar, cuboidal, flat, or hobnail cells with large nuclei and prominent nucleoli separated by a thin fibrotic stroma. In all TCCKs, the majority of neoplastic cells showed immunohistochemical (CD10(+), RCC(+), vimentin(+), and AMACR(+)) and ultrastructural (abundant long brush border microvilli) characteristics of proximal renal tubules. In few cells, the microvilli were shorter and sparse with cytoplasmic interdigitation analogous to intercalated cells of the collecting ducts. Focal positivity for BerEP4 (a marker preferentially expressed in distal renal tubules) was also noted. The major differential diagnostic considerations are oncocytoma, multilocular cystic renal cell carcinoma, and cystic nephroma/mixed epithelial and stromal tumor of the kidney. TCCK seems to have a favorable prognosis. In the current series, none of the patients had local recurrence or metastatic disease.


Asunto(s)
Carcinoma/ultraestructura , Neoplasias Renales/ultraestructura , Adulto , Anciano , Carcinoma/metabolismo , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/metabolismo , Masculino , Microscopía Electrónica de Transmisión
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