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Objectives: To explain the high incidence of misdiagnosis of angiomyolipoma (AML) prior to surgery., Materials and Methods: Between 1989 and 2007, 2,657 patients were operated for a renal tumor at Dupuytren hospital in Limoges and at Cochin hospital in Paris. In 85 cases (3.2%), tumors were AMLs on pathology. The group of patients in which the diagnosis was done preoperatively was compared to the one in which the diagnosis was missed., Results: Mean age of patients was 57-years-old and the sex-ratio was five women for one man. The mean size of AMLs was 5.4 cm. The patients were symptomatic in 46% of cases (39/85). The diagnosis of AML was ignored preoperatively in 62 patients (73%). In multivariate analysis, the small size of the AML, low proportion of fat and male sex were significantly associated with misdiagnosis of AML (p<0.001, p<0.018 and p<0.008, respectively)., Conclusions: The incidence of misdiagnosis of AML preoperatively is high. The diagnosis seems particularly difficult when the tumor is small or contains a small proportion of fat. In addition, this study highlights that the diagnosis of AML is frequently ignored in men. The increased resolution of CTscan and the use of preoperative biopsies for tumors less than 4 cm could be helpful to decrease the incidence of useless surgery of AMLs.

A distinctive tumor described under the terms Bellini duct carcinoma and low-grade collecting duct carcinoma has been referred to by us and others as tubulocystic carcinoma. This renal cell carcinoma subtype is not recognized in the World Health Organization 2004 classification. Herein, we present a detailed study of 31 cases to further characterize this rare subtype of renal cell carcinoma. The tumor occurred in adults (mean age, 54 years) with a strong male predominance (7:1). Grossly, the tumors ranged from 0.7 to 17 cm, and exhibited a spongy or "bubble wrap" appearance reflecting the microscopic presence of variably sized cystically dilated tubules lined by a single layer of epithelium. The lining varied with a cuboidal, flat, and hobnail cell appearance, and the neoplastic cells had abundant eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. The cysts were closely spaced with an intervening variably fibrotic stroma. Immunohistochemistry and ultrastructural examination showed features of proximal convoluted tubules (Pax 2 immunoreactivity and short microvilli with brush border organization) and distal nephron (kidney-specific cadherin immunoreactivity and cytoplasmic interdigitation). Gene expression profiling showed that tubulocystic carcinoma displayed a unique molecular signature. Twenty-four tumors were stage pT1, 4 stage pT2, and 3 stage pT3. Disease progression (median follow-up of 56 months) occurred in 3 patients; 1 with local recurrence, and 2 with distant metastasis to bone and liver. In light of the distinctive clinicopathologic features and a low but definite metastatic potential, this unique subtype of renal cell carcinoma deserves formal recognition in the contemporary classification of renal neoplasms.

Tubulocystic carcinoma is a tumor entity, which is not yet included in the WHO-classification of renal tumors. We report a series of 11 cases of this tumor, 6 of which were examined in by immunohistochemistry using a panel of five antibodies (CK7, CK34betaE12, CK19, CD10 and P504S). All patients were men. Each had renal tumor stage of pT1N0M0, with a diameter of 1.7 to 7 cm (mean, 3.3 cm). None of the patients presented with recurrence or metastases. Grossly, tumors were microcystic masses with a bubble-wrap appearance. Histological features included cysts and small tubules, separated by delicate septa and lined by flat to columnar or hobnail cells. The cyst and tubule epithelium showed immunohistochemical characteristics of both proximal and distal tubules. Tubulocystic carcinoma is a distinctive kidney tumor, with noteworthy macroscopic and microscopic characteristics, which can be distinguished from other cystic kidney tumors, including cystic nephroma, multilocular cystic renal cell carcinoma and some solid tumors with extensive cystic changes. More cases are needed to ascertain its prognosis. Tubulocystic carcinoma should be considered as a new subtype of renal cell carcinoma in the next revision of the WHO classification.

The pancreas is an uncommon site of metastasis from renal cell carcinoma. The metastasis is generally diagnosed during the follow-up of patients who underwent nephrectomy for renal cell carcinoma. In our observation, duodenal bleeding led to the diagnosis of both pancreatic metastasis and renal carcinoma. The diagnosis of pancreatic metastasis should be suspected when a pancreatic mass is associated with past or synchronous renal carcinoma. The outcome after resection of pancreatic metastasis is better than after resection of pancreatic adenocarcinoma. Surgical resection of pancreatic metastasis should be considered when possible.

Background: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor., Objective: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell)., Design: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases., Results: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin., Conclusion: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

Aims: Renal lesions in von Hippel-Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship., Methods and Results: To investigate such a possible relationship between cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel-Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (alpha3, alpha5, alpha6, alphav, beta1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl-2) inconspicuous., Conclusions: Phenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel-Lindau disease.

Renal metastasis from carcinoma of the lung is rarely a clinical problem. Autopsic series however prove that the kidney is a frequent metastatic organ (20%). We report the case of a 43-years-old male patient affected with a squamous cell carcinoma of the lung, with bilateral renal extension. These secondary localizations were detected through a left flank pain prior to a systemic inflammatory response syndrome. The absence of hematuria (even microscopic) contrasted with the importance of the lesions. The age, along with the poor general state of our patient and the absence of any CT specificity justified an exploratory lobotomy. The pathologic analysis of the renal biopsies confirmed the metastatic nature of the lesion.

The purpose of this study is to provide an updated pathologic-radiologic classification of cystic renal tumors and to assess imaging diagnostic capabilities. Eighty seven cases of cystic renal tumors explored with multimodality imaging (ultrasonography, CT, MRI, arteriography) and with histopathologic correlation are reported. The most common cystic carcinomas were multilocular cystic renal cell carcinoma (33%) and the pseudocystic necrotic carcinoma (31%), which usually belong to category IV. Less common cystic carcinomas were unilocular cystic renal cell carcinoma (6%) and renal cyst wall carcinoma (6%). The association of thin septa and large locules are suggestive findings for multilocular cystic nephroma, but such criteria are not specific enough to recognize benign multilocular cystic nephroma and to exclude multilocular cystic renal cell carcinoma. Since carcinomatous degeneration may occur within the wall of such tumors, especially in von Hippel Lindau disease, surgery is still required. The results of our study corroborate the Bosniak classification of cystic renal masses: no tumors belonged to the category I or II, all cystic masses which belonged to the category IV were malignant tumors, category III included benign and malignant tumors.

Unusual fat-containing renal tumors in a series of 27 cases comprised five categories: atypical and complicated angiomyolipomas (AMLs) (n = 15), including AMLs with extrarenal growth (n = 5), AMLs with undetectable fat (n = 4), and hemorrhagic AMLs (n = 6); fat-containing renal cell carcinomas (RCCs) (n = 9); lipoma (n = 1); liposarcoma (n = 1); and fat-containing renal oncocytoma (n = 1). Fat was present within RCCs by the following mechanisms; lipid-producing necrosis within a large RCC (n = 2), intratumoral bone metaplasia with fatty marrow elements and calcification within a small RCC (n = 2), and entrapment of perirenal (n = 4) or sinus (n = 1) fat by large irregular RCCs. Fat-containing RCC must be considered in cases of fat-containing renal tumors, even though the presence of intratumoral fat is characteristic of AML. A dedicated computed tomography scanning protocol and strict diagnostic criteria are mandatory for accurate diagnosis. Malignancy should be suspected on the basis of the following criteria: presence of intratumoral calcifications; large, irregular tumor invading the perirenal or sinus fat; large necrotic tumor with small foci of fat; and association with nonfatty lymph nodes or venous invasion.

Expression of bcl-2 is associated with inhibition of apoptosis and extension of cell survival. The importance of apoptosis in relation to the development and progression of renal cell neoplasia remains undefined so far. In order to determine the expression of bcl-2 oncoprotein in normal and neoplastic renal cells, 37 renal tumours were investigated by immunolabelling, including 13 clear cell carcinomas, ten tubulopapillary carcinomas, four chromophobic renal cell carcinomas, and ten oncocytomas. Twenty-six samples of adjacent normal renal tissue served as controls. bcl-2 expression was correlated with cell proliferation activity as estimated by Ki67 antigen expression, and p53 protein expression in the tumour samples. The results demonstrate that in the normal kidney, positive bcl-2 immunostaining was present in glomerular parietal epithelial cells, in distal tubular cells, and in sparse proximal tubule cells. Renal cell tumours showed heterogeneous bcl-2 expression according to the tumour cell type. While the majority of carcinomas of clear cell type were usually negative or contained sparsely distributed positive cells, all tubulopapillary carcinomas were consistently positive for bcl-2. In oncocytomas and chromophobic carcinomas, there was a low percentage of bcl-2 immunoreactive tumour cells; some nuclear bcl-2 positivity was detected in one chromophobic tumour. These findings indicate variable bcl-2 oncoprotein expression in different types of renal cell tumours, with the highest level of expression in tubulopapillary carcinomas. No clear relationship was found between nuclear grade, cell proliferation activity, and level of bcl-2 expression. p53 protein was detected in only one tubulopapillary carcinoma.

Background: Cell to cell and cell to matrix interactions play a major role in tumor growth and invasion. Therefore, we studied the composition of extracellular matrices and the distribution of cell adhesion molecules in 50 renal cell tumors of various types and various grades of malignancy as compared with nontumoral kidney., Experimental Design: In the present study, we used immunolabeling with specific antibodies directed against the alpha 1, alpha 2, and alpha 3 chains of collagen type IV; laminin; heparan sulfate proteoglycan; fibronectin; collagen I; collagen III; the alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1, and beta 3 subunits of integrins; and ICAM-1, VCAM-1, and ELAM-1 molecules., Results: In clear cell type carcinomas (24 cases) the basal laminae surrounding the tumor islets contained the alpha 1 and alpha 2 chains of collagen type IV and heparan sulfate proteoglycan in all cases, and laminin in 96% of the cases. The alpha 3 chain of collagen IV was present in only one case, whereas fibronectin, collagen I, and collagen III were detected in nearly 50% of the cases. The tumor cells expressed alpha 3, alpha 6, and beta 1 integrin subunits in all cases, alpha 5 in 25%, alpha v beta 3 in 54%, and alpha 2 in none. ICAM-1 was detected in all cases, and VCAM-1 in 58%. The expression of the alpha 6 subunit was weak in 2 tumors of high grade, whereas the alpha v subunit was expressed in 7 of 14 low grade and in 7 of 10 intermediate and high grade tumors. In tubulopapillary carcinomas with chromophilic cells (12 cases), the most prominent findings were the presence of the alpha 3 chain of collagen IV in tumor basal laminae in 66% and the expression of the alpha 2 integrin subunit by the tumor cells in 58% of the cases, both features characterizing distal renal tubules. In chromophobic carcinomas (4 cases), the tumor basement membranes were tenuous and contained no fibronectin or interstitial collagens. The tumor cells expressed the alpha 6, alpha 2, alpha 3, beta 1, and alpha nu beta 3 integrin subunits but neither ICAM-1 nor VCAM-1 molecules. In oncocytomas (10 cases), the tumor basement membranes contained the alpha 1, alpha 2, and alpha 3 chains of collagen IV, laminin, and heparan sulfate proteoglycan. Fibronectin was not detected, whereas interstitial collagens were present in half of the cases. In all tumors, cells expressed the alpha 6 and beta 1 integrin subunits, whereas alpha 2, alpha 3, and alpha nu beta 3 were present in 30%, 60%, and 90% of the cases, respectively. ICAM-1 and VCAM-1 were not detected. The vascular endothelial cells of the stroma expressed the alpha 1, alpha 5, alpha 6, and beta 1 integrin subunits in all 50 of the studied tumors. In addition, ICAM-1 was detected in 84%, VCAM-1 in 50%, and ELAM-1 in 34% irrespective of tumor cell type, growth, or nuclear grade., Conclusions: These results suggest that each type of renal cell tumor produces particular extracellular matrix components and expresses a characteristic repertoire of cell adhesion molecules, which could provide better understanding of the origin of these tumors. The expression of the alpha nu beta 3 integrin subunit was demonstrated in all types of renal cell tumors and was not found to be related to high grade tumors. Stromal vascular endothelial cells expressed activation molecules VCAM-1 and ELAM-1 in a significant number of cases in both benign and malignant tumors.

It is widely believed that demonstration of fat within a well-marginated renal tumor at computed tomography (CT) is highly suggestive of angiomyolipoma and can rule out renal cell carcinoma. The authors describe a patient in whom CT demonstrated a solid mass containing calcifications and small amounts of fat. Renal cell carcinoma was diagnosed at pathologic examination. The carcinoma had tubular and papillary architectural configurations associated with areas of osseous metaplasia located in the fibrous stroma of the tumor. Renal cell carcinoma should be considered in the differential diagnosis of well-marginated lipomatous renal tumors when intratumoral calcifications are identified at CT. Such calcified, fat-containing renal tumors must be evaluated with surgical exploration and treated as any other indeterminate renal tumors.