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Stephen M Bonsib

Publications and source records attributed to Stephen M Bonsib.

11 recordsLinked to original sources
PubMed2006

Renal veins and venous extension in clear cell renal cell carcinoma.

The 2002 TNM formulation defines a pT3b tumor as one that 'extends into the renal vein or its segmental (muscle containing) branches.' This definition elicits uncertainty when veins with little muscle are involved or the relationship to the main renal vein is unknown. The diameter and medial thickness of 10 normal renal venous systems were studied and compared to sinus veins involved in 54 pT3b clear cell renal cell carcinomas (CC). All tumors were grossly examined and sampled for histology by the author. An immunoperoxidase cocktail containing CD 31 and actin, Masson trichrome and elastic stains were employed to aid identification of intravenous tumor. The venous dissections showed variable numbers of primary and secondary divisions with substantial overlap in diameter and medial thickness. The medial thickness decreased with each proximal division and ranged from being nonexistent to being thick. Study of the 54 pT3b CC revealed that the initial phase of extrarenal extension involved large caliber veins draining the primary tumor. With extensive venous involvement, tumor invaded through the vein wall into sinus fat or demonstrated retrograde venous extension into adjacent cortex. Correlation between gross and histology revealed that most nodules of tumor within the sinus fat contained evidence of pre-existing veins. The following observations were made: (1) the diameter of a sinus vein or the quantity of muscle is a poor indicator of vein segment or relationship to the main renal vein; therefore, the wording used to define pT3b should be clarified; (2) extrarenal spread in CC begins with intravenous extension whereas sinus fat invasion is usually secondary; (3) retrograde venous extension occurs in cases with massive renal vein involvement; and (4) nodules within the sinus fat usually represent venous involvement.

Actins↗
PubMed2006

Imaging glomeruli in renal biopsy specimens.

Glomerular capillary loops are complex vascular filters composed of interdigitating podocytes and fenestrated endothelial cells with an intervening proteoglycan-rich extracellular matrix. This arrangement is crucial to maintaining the filtration barrier but renders the glomerulus difficult to analyze by conventional two-dimensional histochemical techniques. When pathologic lesions distort glomerular architecture, its complex morphology is even more challenging to interpret. Fortunately, recent advances in microscopes and computer software now enable glomerular enthusiasts to dissect this complex structure with finer detail. In this review we explore the application of new methodologies such as two-photon microscopy that optimize three-dimensional, multicolor imaging and single-cell segmentation of glomerular components.

Animals↗
PubMed2006

Renal lymphatics, and lymphatic involvement in sinus vein invasive (pT3b) clear cell renal cell carcinoma: a study of 40 cases.

Although renal sinus vein invasion is the most common site of extrarenal involvement in clear cell renal cell carcinoma (CC), CC also spreads by lymphatics. As cortical lymphatics drain into the sinus, some involved sinus structures may be lymphatics, not veins. This possibility was investigated with podoplanin, a specific lymphatic endothelial marker, in 40 CC with sinus vein invasion. Ten blocks of uninvolved kidney, serving as controls, showed lymphatics within the adventitia of midcortical intralobular arteries. Lymphatics became more numerous and enlarged with progression towards the medulla. No lymphatics were among glomeruli or within the medulla unless associated with inflammation. The largest lymphatics occurred within the sinus, and were also noted within pelvic muscularis, and media of large veins. Intralymphatic tumor was observed and divided into two Groups. Group 1 (four cases) involved lymphatics within the invasive edge of tumors lacking a pseudocapsule. The lymphatics were small (0.045-0.19 mm), irregularly shaped, often incomplete, and contained single cells or small clusters of tumor cells. Group 2 (four cases) involved sinus lymphatics separate from tumor. One case each also involved adventitial lymphatics of an intralobular artery, the muscularis of the renal pelvis, and media of a muscular vein. The intralymphatic tumor in Group 2 often appeared discohesive, not endothelial cell invested, and larger than in Group 1 (0.4-0.5 mm). Conversely, tumor within muscular veins was cohesive, contained a capillary plexis, and was endothelial cell invested. In conclusion, intralymphatic tumor can be demonstrated in CC. Lymphatic involvement is less frequent than venous involvement and involves smaller structures. The potential for lymphatic spread may not be equal among involved lymphatics. Small peritumoral lymphatics may be destined for destruction by tumor growth. However, involved lymphatics within sinus and associated with renal pelvis, are likely sources for lymphatic spread and lymph node metastases.

Actins↗
PubMed2005

Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas.

PURPOSE: In patients with papillary renal cell carcinoma, it is not uncommon to find two or more anatomically distinct and histologically similar tumors at radical nephrectomy. Whether these multiple papillary lesions result from intrarenal metastasis or arise independently is unknown. Previous studies have shown that multifocal clear cell renal cell carcinomas express identical allelic loss and shift patterns in the different tumors within the same kidney, consistent with a clonal origin. However, similar clonality assays for multifocal papillary renal cell neoplasia have not been done. Molecular analysis of microsatellite and chromosome alterations and X-chromosome inactivation status in separate tumors in the same patient can be used to study the genetic relationships among the coexisting multiple tumors. EXPERIMENTAL DESIGN: We examined specimens from 21 patients who underwent radical nephrectomy for renal cell carcinoma. All patients had multiple separate papillary lesions (ranging from 2 to 5). Eighteen patients had multiple papillary renal cell carcinomas. Seven had one or more papillary renal cell carcinomas with coexisting papillary adenomas. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays were done for six microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p14 (D3S1285), 7q31 (D7S522), 9p21 (D9S171), 16q23 (D16S507), 17q21 (D17S1795), and 17p13 (TP53). X-chromosome inactivation analyses were done on the papillary kidney tumors from three female patients. Fluorescence in situ hybridization analysis was done on the tumors of selected patients showing allelic loss at loci on chromosome 7 and/or chromosome 17. RESULTS: Twenty of 21 (95%) cases showed allelic loss in one or more of the papillary lesions in at least one of the six polymorphic markers analyzed. A concordant allelic loss pattern between each coexisting kidney tumor was seen in only 1 of 21 (5%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the coexisting multiple papillary lesions was seen in two of three female patients. A discordant pattern of X-chromosome inactivation was seen in the tumors of the other female patient. Fluorescence in situ hybridization showed that the majority of tumors analyzed had gains of chromosomes 7 and 17. Two patients had one tumor with chromosomal gain and another separate tumor that did not. CONCLUSION: Our data suggest that, unlike multifocal clear cell renal cell carcinomas, the multiple tumors in patients with papillary renal cell carcinoma arise independently. Thus, intrarenal metastasis does not seem to play an important role in the spread of papillary renal cell carcinoma, a finding that has surgical, therapeutic, and prognostic implications.

Adult↗
PubMed2005

T2 clear cell renal cell carcinoma is a rare entity: a study of 120 clear cell renal cell carcinomas.

PURPOSE: In 2002 the American Joint Committee on Cancer revised the TNM staging system, introducing subclassification for T1 tumors, and invasion of renal sinus fat and sinus veins in categories T3a and T3b, respectively. Since renal sinus invasion represents the most common site of extrarenal extension, the relationship between size, and renal sinus invasion and its effect on the T classification was examined in prospective fashion. MATERIALS AND METHODS: A total of 175 renal cell carcinomas were examined in prospective fashion with careful evaluation for renal sinus invasion. A minimum of 5 blocks of the renal sinus-tumor interface were examined. Tumors were staged using the 2002 TNM formulation. RESULTS: The distribution of tumors types was clear cell renal cell carcinoma (CC) in 120 cases, papillary renal cell carcinoma in 30, chromophobe renal cell carcinoma in 12 and miscellaneous other carcinomas in 13. T classifications correlated with tumor type. Only 3 of 30 papillary renal cell carcinomas (10%) and 2 of 9 chromophobe renal cell carcinomas (16.6%) demonstrated extrarenal extension compared with 59 of 120 CCs (49%) (p <0.01). Renal sinus invasion occurred more often than capsule invasion (49% vs 20%, p <0.01). No tumor invaded the capsule that did not also invade the sinus. Compared with 1.1 to 4 cm CCs, of which 85% were renal limited, only 32% of CCs that were 4.1 to 7 cm (p <0.01) and 3% of those larger than 7 cm were renal limited, that is T1b and T2, respectively. CONCLUSIONS: The incidence of renal sinus invasion increases sharply after tumors exceed 4 cm. T1b CC is uncommon and T2 CC is rare if careful evaluation for sinus invasion is performed.

Adenocarcinoma, Clear Cell↗
PubMed2004

Practice guidelines for the renal biopsy.

Biopsy of the kidney should never be undertaken without careful consideration of the risks vs benefits. Given the importance of a correct diagnosis in the treatment and prognosis of renal disease, the pathological evaluation should use all available modalities. Native kidney biopsies require examination by light microscopy, immunohistochemistry and electron microscopy. The processing of the renal biopsy is complex and requires the support of a fully equipped anatomic pathology laboratory. Technical expertise is required to process the small fragments of tissue and to produce sections of highest quality. The correct diagnosis requires a well-trained renal pathologist with thorough knowledge of not only renal pathology but also renal medicine in order to correlate intricate tissue-derived information with detailed clinical data. In view of the importance and consequences of the pathologic diagnosis, the Renal Pathology Society appointed an Ad Hoc Committee on Practice Guidelines, to define the essential ingredients necessary to provide quality renal pathology diagnoses. This document incorporates the consensus opinions of the committee and the RPS membership at large.

Biopsy↗
PubMed2004

The renal sinus is the principal invasive pathway: a prospective study of 100 renal cell carcinomas.

A total of 100 renal cell carcinomas were prospectively examined for renal sinus invasion, 74 clear cell renal cell carcinomas (CC), 3 renal cell carcinomas, unclassified (RUC), 16 papillary renal cell carcinomas (PapC), and 7 chromophobe renal cell carcinomas (ChC). Using the 2002 TNM staging formulation, 49 tumors were T1, 5 were T2, and 46 were T3 or T4. Renal sinus invasion occurred more often than renal capsule invasion. No tumor invaded the capsule that did not also invade the sinus. Renal sinus invasion correlated with Fuhrman grade; 17% of grades 1/2 tumors invaded the sinus, while 71% of grade 3/4 tumor invaded the sinus (P < 0.001). Sinus invasion correlated with tumor type; 2 of 23 PapC and ChC invaded the sinus compared with 44 of 77 CC and RUC. Sinus invasion occurred in approximately 16% of tumors 1 to 4 cm in size, then abruptly increased for larger tumors (P < 0.001). When tumors are staged by the 1997 and 2002 TNM formulation, renal sinus invasion upstaged 28% of cases stage T1 or T2 by the 1997 formulation, to T3 using the 2002 criteria. In conclusion, renal sinus invasion is the most common site of extrarenal extension of renal carcinoma and correlates with tumor type, grade and size. Appropriate evaluation for sinus invasion reduces the incidence of T1b and T2 CC tumors, limiting prognostic utility and suggesting reassessment of the T1 and T2 stage designations.

Carcinoma, Renal Cell↗
PubMed2004

Podocyte injury associated glomerulopathies induced by pamidronate.

BACKGROUND: Pamidronate has been demonstrated to decrease bone-related complications in multiple myeloma and delay progression of the disease. This has led to its use in supportive and maintenance therapy of myeloma in conjunction with steroids and chemotherapy. It has also been selectively used in patients with breast cancer and other neoplasms. METHODS: We report on five patients who developed glomerular disease induced by pamidronate. Pamidronate was the only drug common to all patients. Tests for hepatitis B and C and human immunodeficiency virus (HIV) were negative for all patients. The first two patients received a high dose of pamidronate for 8 weeks, whereas the other three patients were on monthly therapy for a prolonged period of time. Sources of data included chart review and pathologic analysis of kidney biopsy. RESULTS: Three patients were female and two were males and all were Caucasian, ranging in age from 58 to 71 years. Renal biopsy findings included minimal change disease in two, focal segmental glomerulosclerosis in two, and collapsing focal segmental glomerulosclerosis in one. Immunofluorescence was essentially negative in all cases. Electron microscopy showed variable podocyte injury and extensive foot process effacement. There was no evidence of multiple myeloma-related renal disease. After the biopsy, pamidronate was discontinued and renal function stabilized in all patients except the one with the collapsing variant of focal segmental glomerulosclerosis who required hemodialysis. Three patients had resolution of proteinuria, one patient continued to have proteinuria without deterioration in renal function. CONCLUSION: Pamidronate has been mainly associated with collapsing focal segmental glomerulosclerosis. This report expands that relationship and adds other glomerular diseases linked with podocyte injury. Additional studies are needed to define the cause of the variability of renal histology with this agent.

Aged↗
PubMed2002

Radiation-induced kidney injury: a role for chronic oxidative stress?

Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant glomerulosclerosis and/or tubulointerstitial fibrosis. However, the particular cell types, mediators and/or mechanisms involved in the development and progression of radiation nephropathy remain ill defined. Angiotensin II (Ang II) plays a major pathogenic role; administration of Ang II blockers markedly abrogates the severity of radiation nephropathy in experimental models. Both ionizing radiation and Ang II signal via generation of reactive oxygen species (ROS). Thus, we hypothesized that localized kidney irradiation might lead to a chronic oxidative stress. In view of the difficulty in measuring ROS in vivo we adopted an indirect immunohistochemical approach in which we used a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most commonly used markers of DNA oxidation. The right kidney of 7-8 week-old male Sprague-Dawley rats was removed. Five to 6 weeks later the remaining hypertrophied kidney was irradiated with single doses of 0-20.0 Gy X-rays. Groups of rats, three per dose, were killed at 4, 8, 16 and 24 weeks post-irradiation, their kidneys fixed, and sections stained with the 8-OHdG-specific antibody N45.1. For quantitation of glomerular DNA oxidation with the N45.1 antibody stained sections, 50 glomeruli/animal were counted. The presence of any intensely stained nuclei within the glomerular tuft was scored as positive. Quantitation of tubular DNA oxidation employed a 10 x 10 point ocular grid. Sections were examined at 400 magnification; 250 tubular profiles were counted. All tubules with any nuclear staining were scored as positive.Sham-irradiated kidneys showed little evidence of DNA oxidation over the experimental period. In contrast, localized kidney irradiation led to a marked, dose-independent increase in glomerular and tubular cell nuclear DNA oxidation. This increase was evident at the first time point studied, i.e. 4 weeks after irradiation, and persisted for up to 24 weeks postirradiation. DNA oxidation in the irradiated kidney was only seen in apparently viable glomerular and tubular cells. Thus, while from 16 to 24 weeks post-irradiation structural alterations had progressed to glomerular sclerosis and tubular atrophy, positive staining for 8-OHdG was not observed in severely atrophic tubules. Similarly, fewer positive staining cells were noted in glomeruli undergoing sclerosis, while none were seen in totally sclerotic glomeruli. These data support the hypothesis that renal irradiation is associated with a chronic and persistent oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Differential diagnosis in nephropathology: an immunofluorescence-driven approach.

Evaluation of a renal biopsy can be intimidating, because observational data from histologic stains, direct immunofluorescence (IF), and electron microscopy must be integrated with clinical and laboratory data to arrive at the correct diagnosis. Numerous diagnostic categories usually merit consideration. The typical strategy to diagnose renal disease is heavily weighted toward analysis of the histologic pattern of glomerular injury. This focus on histology is understandable; histologic evaluation was the first analytic probe available and has driven the formulation of classification schemes. Evaluation of IF before review of the light microscopy facilitates diagnostic evaluation, because the possibilities are immediately reduced. This simplifies the crucial final step-clinical and histologic correlation. In this review, I discuss the information content of IF and provide an algorithmic approach to the major renal diseases based on an IF-driven dissection of the differential diagnosis.

Acute-Phase Proteins↗