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Many of the reported oncocytomas have different chromosome abnormalities, indicating that they comprise a cytogenetically heterogenous group of tumors consisting of potentially cytogenetic subgroups. We have performed cytogenetic studies on nine renal oncocytomas. Clonal abnormalities were present in eight tumors. The findings most observed were the loss of the Y chromosome, and abnormalities of chromosomes 1 and 22. We also observed telomeric associations (tas) in two tumors and structural aberrations of chromosomes 9p and 19q, as well as monosomy 10. In two cases we found a similar reciprocal t(5;11)(q35;q13) in two cases. Review of the literature disclosed one other oncocytoma with a t(5;11) (q35;q13). This suggests that t(5;11)(q35;q13) defines a (second) subset of oncocytomas apart from the subgroup specifically associated with the loss of chromosomes 1 and Y.

The current classification of renal-cell adenomas (RCAs) and carcinomas (RCCs) is based on eight basic cell and tumor types (entities) with characteristic morphologic features: (1) RCCs of clear-cell type, (2) RCAs/RCCs of chromophilic-cell type, (3) RCAs/RCCs of chromophobic-cell type, (4) RCCs of duct Bellini type, (5) RCCs of transitional-cell type, (6) RCCs of neuroendocrine type, (7) RCAs of oncocytic type, and (8) RCAs of metanephroid type. Tumors with a proposed histogenesis from the proximal tubule (clear-cell and chromophilic tumors) amount to 85% of renal cancers, whereas tumors with a proposed histogenesis from the connecting tubule/collecting duct (chromophobic-, oncocytic-, and duct Bellini-type tumors) amount to only 11%. The remaining tumor types represent rare entities (less than 1% each). Tumor cytogenetics data confirm the proposed eight morphologic subtypes and give further indications for type-specific tumor development and progression.

The present investigation is based on the morphological analysis of 1224 renal cell carcinomas and 68 renal oncocytomas from the kidney tumor registry of the Institute of Pathology, University of Mainz. The subclassification of epithelial renal cell tumors in 5 basic types (i.e. clear cell type, chromophilic type, chromophobic type, oncocytic type and duct Bellini type) as proposed by Thoenes and coworkers (1986) was taken as the basis for a systematical study. It refers especially to ultrastructural aspects and antigen profiles of the tumor cells established immunohistologically in relation to the nephron/collecting duct epithelia. Thus, the study focuses on problems of phenotypia and histogenesis. Finally, morphological parameters of prognosis in renal cell carcinomas are taken into account as well. I. Ultrastructural analysis provides further knowledge of the morphological differences between the various basic cell types of epithelial renal tumors. Structural similarities are presented between the basic cell types of clear cell and chromophilic renal cell carcinomas and cells of the proximal tubules, on the one hand, and the basic cell types of the chromophobic renal cell carcinomas, duct Bellini carcinomas as well as oncocytomas and cells of the collecting duct, on the other hand. This can sometimes be traced back to the single cell level (chromophobic renal cell carcinomas: intercalated cell type B). The results of the freeze fracture analysis confirm this view and, for the first time, morphologically prove molecular anomalies of the oncocytic mitochondria membrane. Initial tumor development can be observed for the chromophilic renal cell carcinoma, the duct Bellini carcinoma, as well as the renal oncocytoma and chromophobic renal cell carcinoma. This development demonstrates the relationship these tumor types have to well-defined segments of the nephron/collecting duct (i.e. proximal tubule, medullary and cortical collecting duct). II. The immunohistological analysis demonstrates characteristic antigen profiles of every renal tubule segment and of every epithelial renal tumor type which can be used for differential diagnosis purposes. Two tumor groups with different morphological phenotypes can be identified. The first group (clear cell and chromophilic renal cell carcinomas) mostly presents antigens of the proximal tubule, while the second group (chromophobic renal cell carcinomas, duct Bellini carcinomas, oncocytomas) mostly expresses antigens of the collecting duct. In the case of the renal oncocytomas, for example, the expression of the band 3 antigen exhibits a relationship to the single cell level (i.e. the intercalated cells type A).(ABSTRACT TRUNCATED AT 400 WORDS)

1. Only clear cell and chromophilic carcinomas of the kidney exhibit a considerable lymphocytic infiltration which is compatible with some immunological responsiveness. Chromophobic carcinomas and benign oncocytomas seem to be immunologically reactive. This reflects the different antigen spectrum and histogenesis of these tumors (Störkel and Jacobi, 1989). Clear cell and chromophilic carcinomas are derived from the proximal tubule and chromophobic carcinomas and oncocytomas from the collecting duct. 2. The tumor periphery seems to be the place of greatest immunological importance, as basic requirements of a sufficient lymphocyte/tumor cell interaction can only be expected there. If these data are taken into account for a therapeutical approach with biological immune modifiers the size of the tumor (tumor burden) and proliferation index must be considered too. This might be a likely explanation for the positive effect of inhaled interleukin-2 on lung metastasis in renal cell cancers. Harvesting of tumor infiltrating lymphocytes for therapeutical purposes should take these findings into account. 3. In spite of dense lymphocytic infiltration only 3% of the tumor infiltrating lymphocytes exhibit the activation marker CD 25. There seems to be a sufficient T cell locomotion in renal cell carcinomas but an insufficient T-cell activation. Whether this fact is induced by lacking cytokine stimulation of involved lymphocytes or by still unknown mediators of the tumor cells is not yet known and needs further investigation. 4. Clear cell carcinomas exhibit most adhesion molecules and the highest amount of infiltrating cytotoxic T-cells and natural killer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The term renal cell tumors (adenomas and carcinomas) subsumes the tumors deriving from the uriniferous tubule epithelium of the kidney. Precise analysis shows that the renal cell tumors display different cell types which build up the individual tumor alone or in combination with each other. Three categories of basic elements are distinguished in the characterization of renal cell tumors: Cytological elements = tumor cell types: Clear, chromophobe, chromophilic (basophilic, eosinophilic), oncocytic, spindle-shaped/pleomorphic. Histological elements = growth patterns: Compact, acinar (nest-like), tubulopapillary (tubular, papillary), cystic. Cytological grading of malignancy: G I, G II, G III; mainly based on the degrees of nuclear atypia. The cytological features are given priority compared to the histological growth forms for classification of renal cell tumors. However, the latter are not to be neglected in the overall evaluation of a tumor. A classification of renal cell tumors is suggested and the result of its application in 510 renal cell carcinomas and oncocytomas is presented. On this basis and in connection with the cytological grading, a more precise prognostic evaluation of the renal cell carcinomas is expected.

The angiographic findings in ten patients with renal oncocytoma are described. Characteristic features include: absence of encasement, vascular occlusions, arterio-venous shunts and contrast lakes (8/10). Spoke-wheel arrangement of tumor vessels (8/10). Homogeneous tumour contrast during the capillary phase (7/10). Sharp demarcation from the kidney and surroundings (9/10) and a peritumoral halo (4/10). If the suspicion of an oncocytoma is raised by CT examination of a space-occupying lesion (part I), angiography should be performed to confirm the diagnosis and help in planning surgical treatment.

Renal oncocytoma is a distinct type of epithelial tumor said to arise from the collecting duct system. Here we show that in nine of ten oncocytomas the tumor cells expressed an analog of the erythrocyte anion exchanger band 3. In the normal kidney band 3 is confined to the basolateral surface of the majority of intercalated cells which comprise up to 50% of the cortical collecting duct epithelium. Carbonic anhydrase c is another protein abundant in intercalated cells, and this was also expressed in six of the ten oncocytomas investigated. Immunoreactivity specific for band 3 and carbonic anhydrase c was not detected in any of the 20 renal cell carcinomas examined. At favourable section planes direct transitions between normal collecting ducts and oncocytic tubules were observed. These findings suggest that oncocytomas may develop from intercalated cells of the collecting duct epithelium.

The computer tomograms of 22 patients with renal oncocytomas were analysed retrospectively. Characteristic findings were: 1. solid round space-occupying lesions (22/22), 2. sharp demarcation from the kidney (20/22), 3. smooth margin (20/22), 4. hypodensity after intravenous contrast (20/20), 5. enhancement (19/19), 6. central hypodense nidus (16/22), 7. homogeneous beyond the nidus (11/22). In the presence of these criteria, the diagnosis of an oncocytoma may be suspected. Safe differentiation from a renal cell carcinoma may not always be possible.

Typing of renal cell tumours according to cytomorphological criteria results in different basic cell types, i.e. the clear cell type, the chromophilic cell type, the chromophobic cell type, the oncocytic cell type and the cell type of Duct-Bellini-Carcinoma. Each basic cell type exhibits a typical spectrum of cytological variability including eosinophilic (granular) variants. Antigenic properties of the proximal tubule can mainly be detected in clear cell and chromophilic renal cell carcinomas, whereas antigenic properties of the connecting tubule and collecting duct can be found especially in the chromophobic renal cell carcinoma and oncocytoma as far as in Duct-Bellini-Carcinoma. These different phenotypes of epithelial renal cell tumours are possibly due to various histogenetic pathways. Prognostic factors in renal cell carcinoma include staging, grading and to a less extent cytological and histological parameters which are summarized in a new prognostic score. From this score, three significantly distinct prognostic groups evolved with a correct prognosis of over 80% on the average for an individual case, which suggests a great prognostic potential.

We examined the expression of the diverse cytokeratin (CK) polypeptides as well as vimentin in human renal cell carcinomas of various subtypes and in renal oncocytomas by applying both two-dimensional gel electrophoresis and immunocytochemistry by using polypeptide-specific monoclonal antibodies. The tumors were classified according to the guidelines of the World Health Organization, with some modifications based primarily on recently proposed cytomorphological criteria. All clear cell carcinomas (G I, G II; N = 20) co-expressed CKs nos. 8 and 18, and vimentin, with CK no. 19 being present in 13 of the 20 cases and exhibiting a heterogeneous distribution. Dedifferentiated carcinomas (G III; N = 8) also co-expressed CKs nos. 8 and 18 as well as vimentin, but in addition, exhibited CK no. 19 and, in many cases, CK no. 7; in 1 case, only vimentin was expressed. Both eosinophilic-granular (N = 3) and basophilic (small cell cuboidal; N = 6) carcinomas contained CKs nos. 8 and 18, and the co-expression of vimentin was a consistent feature of these tumors; CK no. 19 was found in all of these cases, while CK no. 7 was present in the majority. In chromophobe cell carcinomas (N = 8), in contrast to all of the other carcinoma types, no vimentin was detected in the tumor cells, with only CKs nos. 8, 18, and to a variable extent 7, being present. Similarly, oncocytomas (N = 8) lacked vimentin and exhibited only CKs nos. 8 and 18. Conspicuous scattered CK no. 19-positive cells were found in these two last tumor types. No CK polypeptides other than simple-epithelium-type CKs (nos. 7, 8, 18, and 19) were detected in any of the tumors studied. These results indicate that, in renal cell tumors, the expression of intermediate-filament proteins is strikingly correlated with the specific morphologic appearance. While the co-expression of CKs nos. 8 and 18 and vimentin was a surprisingly consistent feature of the most common subtypes of renal cell carcinomas, CK no. 19 exhibited remarkable heterogeneity of expression both within individual tumors and between different tumors, the expression patterns of this CK being correlated to the tumor subtypes. The consistent absence of vimentin in chromophobe cell carcinomas and oncocytomas makes it possible to define these as a separate class of renal cell tumors. This finding supports the view that chromophobe cell carcinomas represent a distinct tumor entity and points to their close phenotypic relationship to benign oncocytomas as well as to normal renal tubules.