Intan P.E.D. Kümmerlin

Biopsy of a renal mass: where are we now?

Purpose of review To review the most recent literature concerning renal mass biopsy with special consideration to three points: variation in results related to the standard used as comparison, biopsy in small renal masses (up to 4 cm in diameter) and the case for nondiagnostic biopsy. Recent findings The overall rate of failed and indeterminate biopsies shows a trend for improvement. However, selection bias and the lack of a uniform index test for comparison preclude a definitive statement. Fine-needle aspiration may equal results of core biopsy, but its role in the diagnostic algorithm is not yet defined. In-vivo accuracy decreases in small renal masses with the same limitations exposed for the overall literature on renal mass biopsy. When nondiagnostic biopsies are considered, there is a need for standardization of the nomenclature in order to compare results. Re-biopsies or surgery after a nondiagnostic biopsy shows malignancy in up to 75% of the cases of renal cell carcinoma. Summary There is a trend in increasing interest and accuracy on the subject of percutaneous biopsy of renal masses as well as a decreasing trend in the rate of nondiagnostic biopsies. In the small renal masses, most likely to be benign, a diagnostic percutaneous biopsy may have a definitive role. However, the higher rate of nondiagnostic results in this population calls for prospective studies with standard definitions and when possible homogenous index test to properly assess the diagnostic performance of the biopsy.

Cytological Punctures in the Diagnosis of Renal Tumours: A Study on Accuracy and Reproducibility

BACKGROUND Fine needle aspiration (FNA) cytology is under consideration as an auxiliary preoperative diagnostic technique in the diagnosis of renal masses. However, reports for FNA are contradictory with regard to diagnostic accuracy and applicability. OBJECTIVE To evaluate the diagnostic accuracy and reproducibility of FNA from renal masses. DESIGN FNAs performed in-bench (hematoxylin and eosin [H&E] stains) from 66 consecutive renal tumours (58 malignant and 8 benign tumours) were presented twice with a 6-mo interval to five pathologists with little experience in renal cytology. Pathologists were blinded for the results of the first round as well for the surgical specimen. The FNAs were stained for Papanicolaou and Giemsa. MEASUREMENTS Diagnostic accuracy, concordance between smears and surgical specimens, and the generalized kappa for interobserver/intraobserver agreement were calculated. RESULTS AND LIMITATIONS The number of nondiagnostic and nonconclusive cases ranged from 5-14% in the first and 3-8% in the second round. Overall accuracy varied between 73-89% and 71-91% for the first and second round, respectively. Sensitivity (72-97%) and positive predictive value (PPV) (93-100%) to classify a malignant tumour in both rounds was high. Sensitivity (25-100%) and PPV (28-100%) to classify a benign tumour was lower with a wide confidence interval. Overall concordance in subtyping ranged from 39-70% in the first, and from 52-74% in the second round. Interobserver agreement ranged from fair (kappa=0.039) to substantial (kappa=0.540) for the different subtypes. The intraobserver agreement (mean kappa=0.357, CI 95%=0.304-0.411) was moderate for all pathologists. The low number of benign tumours in this study precludes sound statements regarding the diagnostic accuracy of FNA to classify benignity. CONCLUSION Despite the lack of experience in renal cytology, all pathologists showed a high diagnostic yield and good overall accuracy in distinguishing between malignant and benign tumours. Concordance in subtyping varied widely among pathologists and was reliable only for clear cell renal cell carcinoma (ccRCC). These results suggest that FNA may have a potential role in the diagnosis of renal tumours although its value in subtyping was limited in our setting.

NADPH production by the pentose phosphate pathway in the zona fasciculata of rat adrenal gland

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was ∼60%, 15%, and 7% of G6PD activity, respectively. The Km value of G6PD for glucose-6-phosphate was two times higher than the Km value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6PD.

Changes in the stage and surgical management of renal tumours during 1995–2005: an analysis of the Dutch national histopathology registry

To evaluate changes in the pathological characteristics, stage of primary renal tumours and their surgical management in the Netherlands during the period 1995–2005.

Age and Gender Related Differences in Renal Cell Carcinoma in a European Cohort

PURPOSE We evaluated the influence of age on gender related differences in the renal cell carcinoma presentation of patients operated on between 1995 and 2005 in a European country. We also assessed the trend of missing pathological data. MATERIALS AND METHODS Data on all patients who underwent radical or partial nephrectomy for renal cell carcinoma during 1995 to 2005 in The Netherlands were retrospectively collected from the prospective PALGA (Pathological Anatomical National Automated Archive) database. Patients were divided into 5 cohorts based on age at surgery, including 40 or less, 41 to 50, 51 to 60, 61 to 70 and greater than 70 years. Variables evaluated were gender differences by age, and tumor size, subtype, stage and Fuhrman grade. RESULTS A higher mean age in women was only observed in those older than 70 years (p <0.001). The male-to-female ratio was 2:1 at ages 41 to 60 years and 1.2:1 at greater than 70 years. Compared to men women had smaller tumors at ages 51 to 60 years (p = 0.03), stage pT3 was less common at age 41 years or greater (p = 0.02), and grade 2 was less common at age 61 years or greater (p <0.001). The incidence of tumors with missing data on stage (14.9%), subtype (52.2%) and grade (47.1%) decreased substantially during the study period (p <0.001). CONCLUSIONS Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.

Diagnostic problems in the subtyping of renal tumors encountered by five pathologists

The diagnostic problems in the subtyping of renal tumors were evaluated by a panel of five pathologists studying a set of selected tumors. Five pathologists independently assessed a single hematoxylin-and-eosin (HE)-stained slide from 28 selected renal tumors. After this independent assessment, the pathologists reevaluated and discussed all discordant cases. Additional HE-stained sections and immunohistochemically (IHC) stained slides were available. The generalized kappa for interobserver agreement was calculated. After independent assessment of the HE-stained slides, the five pathologists unanimously reached an agreement in the decision between malignant and benign in 82% of the cases. Fifty percent of the cases were correctly subclassified. The overall generalized kappa value for the five pathologists was 0.320 (CI 95% 0.090-0.551), which is considered a moderate agreement. A 100% agreement was reached for all 28 cases after examination of more slides from different tumor areas and IHC-stained sections. An accurate histologic distinction between benign and malignant renal tumors is possible on one HE-stained section. Correct assignment of the subtype is difficult on one slide alone and relies on IHC-markers and additional slides. Tumors composed of an eosinophilic cell type and tumors with a papillary growth pattern were the major causes of an incorrect diagnosis on an HE-stained section alone.

Trends in epidemiology and treatment of upper urinary tract tumours in the Netherlands 1995-2005: an analysis of PALGA, the Dutch national histopathology registry

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

Crioablación laparoscópica de las pequeñas masas renales

Resumen Objetivos Revision del estado actual de la crioblacion de las pequenas masas renales y descripcion preliminar de la serie del AMC. Material y metodos Busqueda bibliografica (PubMed/Medline/Embase) y analisis de las series mas importantes. La presente serie incluye 13 pacientes portadores de masas renales unicas de pequeno tamano tratados mediante crioablacion laparoscopica con sondas ultrafinas (1,5 mm diametro). El seguimiento postoperatorio se realizo mediante CT y/o RMI trimestralmente durante el primer ano y semestralmente durante el segundo. Resultados No existen estudios randomizados comparando la crioablacion de las masas renales de diametro ≤ 4 cm con la cirugia parcial o radical. La tasa de complicaciones es baja y la tasa de recurrencia o persistencia, a corto plazo, minima salvo en una serie de crioablacion guiada por la imagen (8%). El diametro tumoral maximo tratado en nuestra serie es de 3,2 cm. Los tumores se abordaron retro o transperitonealmente dependiendo de su situacion. El tiempo quirurgico medio fue de 208 minutos (106-379) y el tiempo medio de exposicion a temperaturas inferiores a -20oC en la periferia tumoral fue de 10 minutos. A tiempo medio de seguimiento de 8 meses no se objetivo recurrencia tumoral. Conclusion La crioablacion laparoscopica o guiada mediante imagen de las masas renales de pequeno tamano parece una alternativa aceptable si bien el tiempo medio de seguimiento es todavia corto en la mayoria de las series.