Primary renal glomus tumor with concurrent papillary renal cell carcinoma and multiple papillary adenomas in a patient with end stage renal disease: a case report and clinicopathologic analysis

Glomus tumors are mesenchymal tumors commonly seen in the extremities, and rarely seen in deep visceral organs. This is due to the lack of glomus bodies in visceral organs. Here, we describe an unusual association between glomus tumor and co-existing papillary renal cell carcinoma, multiple papillary adenomas, and end stage renal disease. We discuss our diagnostic approach and differential diagnoses, along with an extensive review of all reported benign and malignant primary glomus tumors. A 63-year-old male with a known history of a kidney transplant, end-stage renal disease, and previous nephrectomy of his right kidney due to a renal mass (papillary renal cell carcinoma) presented with a renal mass. Microscopic examination showed papillary carcinoma, multiple papillary adenomas, and a small nodule with uniform, round to oval cells. Immunohistochemical work-up revealed the small nodule to be a glomus tumor. Only 28 cases of primary renal glomus tumors have been reported in the literature. Most were discovered incidentally. None of the reported cases have occurred along with other renal tumors. This is the first case of the unusual combination of primary renal glomus tumor arising in the native kidney of a renal transplant patient with concurrent papillary renal cell carcinoma and multiple papillary adenomas (renal adenomatosis). We also explore the possible genetic basis behind this association.     

Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnostics

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.     

NCAM and FGFR1 coexpression and colocalization in renal tumors

Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor (FGFR) have a role in epithelial-mesenchymal transformation during tumor genesis. Interplay between both molecules activates FGFR signaling and it could be responsible for tumor development. Renal epithelial tumors were analyzed for FGFR1 and NCAM coexpression by immunohistochemistry and for colocalization of these molecules on the particular tumor cells by triple immunofluorescence. Detection of NCAM isoforms in renal tumors was evaluated by RT-PCR. Applying immunohistochemistry we revealed that the majority of analyzed renal neoplasms, including renal cell carcinoma (RCC) and oncocytoma coexpressed NCAM and FGFR1. Triple immunofluorescent technique confirmed that both markers are commonly colocalized on the same tumor cells. Interestingly, it seemed that different position of NCAM and FGFR1 expression on renal tumor cells is related to renal tumor type or grade: exclusively membranous FGFR1/NCAM expression occurred in low grade clear cell RCC (cRCC); cytoplasmatic and membranous expression was present in high grade cRCC and other RCC types; oncocytoma showed only cytoplasmatic staining of both markers. NCAM-140 and NCAM-120 were detected in almost all analyzed renal neoplasms. Expression of both molecules on different cell compartments in various kidney tumors indicated that NCAM/FGFR1 interaction could play distinct roles in renal tumor genesis.     

A novel case of concurrent renal tumors: chromophobe renal cell carcinoma and carcinoid tumor of the kidney with brief review of renal neuroendocrine tumors

Renal cell carcinoma of chromophobe type is a malignant neoplasm with characteristic large cells that exhibit prominent cell membranes. Primary renal carcinoid tumors are rare tumors with the histological appearance similar to well-differentiated neuroendocrine tumors at other sites. Chromophobe renal cell carcinoma with neuroendocrine differentiation is exceedingly rare. The authors describe a case of a chromophobe renal cell carcinoma and carcinoid tumor of the kidney presenting as distinct masses in the same kidney in a 34-year-old male. The histologic and immunohistochemical features of both the tumors were characteristic with no overlapping features. The carcinoid tumor presented at a higher stage with nodal metastasis. To the best of the authors' knowledge, this is the first case of 2 morphologically distinct tumors, one chromophobe renal cell carcinoma and the other primary carcinoid tumor in the same kidney.     

Benign tumors and tumor-like lesions of the adult kidney. Part II: Benign mesenchymal and mixed neoplasms, and tumor-like lesions

In this review article the benign tumors and tumor-like lesions of the adult kidney are discussed. The incidence of benign renal tumors is low, especially when compared to renal cell carcinomas, as most are detected incidentally or at autopsy. Some of these tumors, as their names imply, are unique to the kidney, e.g., renal adenoma, metanephric adenoma, renal oncocytoma, nephrogenic adenofibroma, mesoblastic nephroma, capsuloma, juxtaglomerular cell tumor, renomedullary interstitial cell tumor (medullary fibroma), cystic nephroma, cystic partially differentiated nephroblastoma, and cystic hamartoma of the renal pelvis, while others, such as angiomyolipoma, leiomyoma, hemangioma, lipoma, etc., are not unique to the kidney and show similar morphologic features in the other sites they affect. Of the tumor-like lesions, xanthogranulomatous pyelonephritis, malakoplakia, and renal cysts are the most common. The other entities, such as fibroepithelial polyp, are rare, most having been the topic of case reports. In Part I of this paper the benign epithelial tumors of the kidney were previously discussed. This paper (Part II) is devoted to the benign mesenchymal tumors, mixed mesenchymal and epithelial tumors, and the tumor-like lesions.     

Renal cell adenomas and carcinomas in hemodialysis patients: Relationship between hemodialysis period and development of lesions

Step-sections of 96 whole kidneys from 50 chronic hemodialysis patients were subjected to a histopathological and quantitative investigation with regard to the development of renal neoplastic lesions. The range of hemodialysis duration was from 1 to 222 months. A total of 349 renal cell adenomas were found in 41 cases (82%). They were commonly multiple and present bilaterally. Renal cell carcinomas were evident in four cases (8%), with hemodialysis durations of 54, 57, 112 and 222 months. The incidence of adenomas increased in a hemodialysis duration-dependent manner, indicating a high risk of renal cell tumor development in chronic hemodialysis patients. Furthermore, acquired cystic disease of the kidney (ACDK) was also observed in 12 cases (24.0%), where the mean hemodialysis period was 143.4 ± 48.0 months. This value was significantly longer than that of non-ACDK cases (P < 0.001). There was, however, no clear relationship between the appearance of ACDK and renal cell tumors. The present results underline the necessity for attention to possible neoplasia of the kidney in patients on long-term hemodialysis.     

Expression of endothelin 2 and localized clear cell renal cell carcinoma

Despite the rising incidence of clear cell renal cell carcinoma, the molecular events that support its development and progression remain unclear. Herein, we evaluate the association of endothelin 2 expression with both clear cell renal cell carcinoma development and progression-free survival. We conducted real-time polymerase chain reaction to determine endothelin 2 expression levels on 238 patients who underwent nephrectomy for localized clear cell renal cell carcinoma, 161 of whom also had adjacent normal kidney samples available for analysis. To evaluate associations with clear cell renal cell carcinoma development, linear mixed models were used to compare differential expression between tumor and a normal kidney as well as to explore interactions with clinicopathologic features. To evaluate associations with prognosis, Cox proportional hazards models were used to assess the association of progression-free survival and endothelin 2 expression in tumor tissue. Overall, endothelin 2 expression was higher in tumor samples versus patient-matched normal kidney samples, with an average fold change of 1.99 (95% confidence interval, 1.48-2.60; P < .0001). This overexpression in tumor versus normal kidney samples was more pronounced in low- compared with high-grade tumors (interaction, P = .0002), in early- compared with late-stage tumors (interaction, P = .001), and in tumors without compared with those with necrosis (interaction, P = .001). Moreover, an increasing endothelin 2 expression in tumors was associated with a longer progression-free survival (hazard ratio, 0.89; 95% confidence interval, 0.80-0.99; P = .03); however, after controlling for known clinicopathologic factors, this association was attenuated (hazard ratio, 0.99; 95% confidence interval, 0.89-1.09; P = .7). Up-regulation of endothelin 2 is a common and early event in localized clear cell renal cell carcinoma. Higher tumor expression of endothelin 2 is associated with a longer progression-free survival but not after adjustment for well-known pathologic indices. Thus, although endothelin 2 does not appear to be an independent prognostic marker, there is evidence of a putative role in clear cell renal cell carcinoma progression. If supportive mechanistic data can be produced, endothelin 2 could represent a potential target for chemopreventive or neoadjuvant therapeutics for clear cell renal cell carcinoma.     

Synchronous squamous cell carcinoma of the kidney,squamous cell carcinoma of the ureter,and sarcomatoid carcinoma of the urinary bladder: A case report

The author presents a unique case of a synchronous triple carcinoma of kidney, ureter, and urinary bladder. A 73-year-old man was admitted to our hospital because of hematuria and lumbago. Endoscopy and imaging modalities revealed a bladder tumor, a left ureter tumor, and a left kidney tumor. No other tumors were found in the body by imaging modalities. Cystectomy and left nephroureterectomy were performed. The bladder tumor was a large polypoid tumor consisting of pleomorphic sarcomatoid carcinoma (80%) and high-grade papillary urothelial carcinoma (20%), both invading the deep muscle layer. There were gradual merges between the two. The sarcomatous component was composed of malignant spindle, polygonal, and giant cells. Lymphovascular permeation was pronounced. Immunohistochemically, the sarcomatous element was positive for vimentin and various types of cytokeratins (CK), while the urothelial carcinoma element was positive for various types of CK and negative for vimentin. The ureter tumor was small and obstructed the ureter lumen. It was a pure squamous cell carcinoma without a urothelial component. The ureter tumor invaded the adventitia. A mild degree of lymphovascular invasion was recognized. Immunohistochemically, the tumor cells were positive for various types of CK but negative for vimentin. In the kidney, almost the entire kidney parenchyma was replaced by a tumor. The renal pelvis was broadly erosive but was free of apparent tumors. Histologically, the renal tumor was a pure squamous cell carcinoma without a urothelial component. Broad necrosis was present, and lymphovascular permeation was pronounced. The renal pelvis and calices were devoid of apparent tumor cells, but renal squamous cell carcinoma was present just beneath the pelvis and calices. Immunohistochemically, the kidney tumor was positive for various types of CK and negative for vimentin.     

Specific genomic alterations in rat renal cell carcinomas induced by N-ethyl-N-hydroxyethylnitrosamine.

To characterize genetic alterations occurring in renal tumorigenesis, EHEN-induced renal cell tumors were examined using restriction landmark genomic scanning (RLGS) analysis, an electrophoretic separation technique that detects gene amplifications and deletions. Comparison of DNAs from tumor against those from corresponding nontumorous kidney and/or EHEN-treated kidney without development of renal tumors yielded specific alterations in terms of both amplified and reduced DNA spots. Two amplified spots were detected only in renal cell tumors and an additional four spots were frequent in EHEN-treated kidneys. One reduced spot was common to all tumor samples, and another was frequently detected in the tumors analyzed but not in EHEN-treated kidneys. A subset of the altered spots thus appeared to be specific for EHEN-induced renal tumorigenesis.     

Cellular congenital mesoblastic nephroma in a newborn

Typical nephroblastoma (Wilms'tumor) is uncommon within the first 6 months of life. Renal tumors most commonly found in this age constitute of two groups which have a better and worse prognosis, respectively, than typical nephroblastomas. The group of tumors with a better prognosis encompasses congenital mesoblastic nephroma (CMN), fetal rhabdomyomatous nephroblastoma and cystic, partially differentiated nephroblastoma. The group of tumors with a worse prognosis consists of rhabdoid tumor of the kidney and bone metastasizing renal tumor (clear cell sarcoma) of childhood. Adequate therapy for these two neoplasms has as yet to be developed. Among the low-grade malignant tumors congenital mesoblastic nephroma can be successfully treated with simple nephrectomy. There, are however, variants of CMN which may differ in clinical behavior from the typical form of CMN. These variants include the cellular CMN2 and, possibly, the malignant mesenchymal nephroma of infancy. A case of cellular congenital mesoblastic nephroma is presented here. Its clinical and pathologic features are discussed.     

EXPERIMENTAL STUDIES ON TUMORS OF THE URINARY SYSTEM OF RATS INDUCED BY CHEMICAL CARCINOGENS*

Tumors in rats were induced in the urinary system of rats with basic lead acetate (BLA), N-nitrosodimethylamine (DMN), N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), N-nitrosodibutylamine (DBN), 3-methylcholanthrene (3-MC) and 4-nitroquinollne 1-oxide (4NQO). These kidney, ureter and urinary bladder tumors were studied by histopatho-logy, histochemistry, autoradiography and electron microscopy. The tumors of the kidney were classified into the following 4 types; renal cell tumors, embryonal cell tumors, transitional cell tumors and hemangioendotheliomas. However, the tumors of all other regions were of one type, transitional cell tumors. Studies by light and electron microscopy and autoradiography and histochemlcal studies on the histogenesis of tumors of the urinary system in rats showed that renal cell tumors may originate from the renal tubular epithelium and from a part of the metanephrogenic tissue, embryonal cell tumors originate from metanephrogenic tissue and hemangioendotheliomas may originate from blood capillaries. Transitional cell tumors of the kidney, renal pelvis, ureter and bladder originate from transitional epithelium.     

Expression of GLUT1 in primary renal tumors: morphologic and biologic implications

This study aimed to assess whether glucose transporter 1 (GLUT1) is useful in prognostication or differential diagnosis of renal tumors. GLUT1 immunostain for 228 renal tumors showed a membranous or cytoplasmic pattern. The membranous pattern was seen in 86.2% of 145 clear cell renal cell carcinomas (RCCs) and 100% of 11 transitional cell carcinomas (TCCs) but in no oncocytomas, other subtypes of RCC, or sarcomatoid areas of RCCs. The cytoplasmic pattern was seen in 55.2% of 145 clear cell RCCs, 38% of papillary RCCs (11/29), 13% of chromophobe RCCs (2/16), 22% of oncocytomas (5/23), and 82% of TCCs (9/11). Western blot showed a markedly increased GLUT1 protein content in clear cell RCCs compared with a low level in papillary RCCs and normal kidney specimens. GLUT1 expression in clear cell RCC was not significantly correlated with patient survival, tumor grade, or tumor stage. GLUT1 may be a novel target for immunotherapy and a useful marker in the differential diagnosis and classification of renal tumors.     

Expression of carbonic anhydrase IX,PAX2 and PAX8 and their association with clinicopathologic characteristics in renal epithelial tumors北大核心CSCD

Objective: To study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics. Methods: Immunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls. Results: CAIX was commonly expressed in CCRCC (94. 0%, 63/67), of which 77. 8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor. Conclusions: CAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.     

DNA methylation profiling reveals novel diagnostic biomarkers in renal cell carcinoma

Background

Renal cell carcinoma (RCC) is the tenth most commonly diagnosed cancer in the United States. While it is usually lethal when metastatic, RCC is successfully treated with surgery when tumors are confined to the kidney and have low tumor volume. Because most early stage renal tumors do not result in symptoms, there is a strong need for biomarkers that can be used to detect the presence of the cancer as well as to monitor patients during and after therapy.

Methods

We examined genome-wide DNA methylation alterations in renal cell carcinomas of diverse histologies and benign adjacent kidney tissues from 96 patients.

Results

We observed widespread methylation differences between tumors and benign adjacent tissues, particularly in immune-, G-protein coupled receptor-, and metabolism-related genes. Additionally, we identified a single panel of DNA methylation biomarkers that reliably distinguishes tumor from benign adjacent tissue in all of the most common kidney cancer histologic subtypes, and a second panel does the same specifically for clear cell renal cell carcinoma tumors. This set of biomarkers were validated independently with excellent performance characteristics in more than 1,000 tissues in The Cancer Genome Atlas clear cell, papillary, and chromophobe renal cell carcinoma datasets.

Conclusions

These DNA methylation profiles provide insights into the etiology of renal cell carcinoma and, most importantly, demonstrate clinically applicable biomarkers for use in early detection of kidney cancer.

     

Intrarenal solitary fibrous tumor of the kidney report of a case with emphasis on the differential diagnosis in the wide spectrum of monomorphous spindle cell tumors of the kidney

Solitary fibrous tumor (SFT) is a neoplasm that can occur in the urogenital tract, and is also reported occurring in the spermatic cord, seminal vesicles, urinary bladder, prostate, and kidney. Furthermore, it is most important to consider its existence in the kidney, because it is usually diagnosed as renal cell carcinoma pre-operatively. To our knowledge, only 10 cases of SFT have been reported in the kidney to date. We report the clinico-pathological features of an intrarenal SFT occurring in a 31-year-old woman. The tumor, measuring 8.6 cm in its greatest diameter, completely replaced the cortex and the medulla of the middle region of the right kidney, compressing the pelvis. Radiological imaging was consistent with a renal cell carcinoma. Histologically, the tumor was composed of a proliferation of bland-looking vimentin+, CD34+, bcl2+ and CD99+ spindle cells exhibiting a haphazard to storiform growth pattern, pushing borders, and a low mitotic rate (2 mitoses x 10 HPF). We placed emphasis on the differential diagnostic problems, i.e., its differentiation from other primary monomorphous benign and malignant spindle cell tumors of the kidney, such as fibroma, benign fibrous histiocytoma, hemangiopericytoma, inflammatory myofibroblastic (pseudo-)tumor, leiomyoma, angiomyolipoma with predominant spindle cell smooth muscle component, benign peripheral nerve sheath tumors, renal mixed epithelial/stromal tumors, adult type mesoblastic nephroma, fibrous type monophasic synovial sarcoma, malignant peripheral nerve sheath tumors, fibrosarcoma, and low-grade fibromyxoid sarcoma.     

Intrarenal schwannoma: a report of four cases including three cellular variants.

Renal schwannomas are extraordinarily rare neoplasms; only six have been reported, the majority of which occurred in the renal pelvis. We report the clinical and pathologic features of four additional cases. The resected kidney in all patients contained a well-demarcated, yellow-tan, smooth, and bulging intraparenchymal tumor (mean size, 9.7 cm; range, 4 to 16 cm). Microscopically, three cases were classified as cellular schwannomas, and one was a usual-type schwannoma, with degenerative nuclear atypia. By immunohistochemistry, all tumors were strongly S-100 protein positive and negative for pan-cytokeratin, CD57, smooth muscle actin, desmin, and CD34. Epithelial elements were not noted in the tumors, and there was no history of any clinical syndromes in these patients. Analysis of the four cases showed the mean age at presentation to be 47 years (range, 18 to 84 years), with no sex predisposition (two men, two women). Most patients were asymptomatic, and all received a diagnosis of renal cell carcinoma and treated as having such. Recognition and awareness of these rare, benign tumors will assist in the differential diagnosis of spindle cell tumors of the kidney and prevent their misdiagnosis as sarcomatoid carcinomas of the kidney or renal sarcomas. Our study, the largest series to date of renal schwannomas, demonstrates a predilection for the cellular variant in the kidney, documents that these tumors may present in the nonhilar region of the kidney, and provides clinical evidence of their benign biologic behavior.     

Renal cell carcinoma with intratumoral calcium oxalate crystal deposition in patients with acquired cystic disease of the kidney

We describe 2 cases of renal cell carcinoma arising in acquired cystic disease of the kidney (ACDK) in patients with end-stage renal disease undergoing hemodialysis for more than 5 years and provide a brief review of the complications of ACDK. In both cases, abundant calcium oxalate crystals were observed within the tumors. Histologically, one of the tumors was a conventional (clear cell) renal cell carcinoma. The other tumor was a bilateral papillary renal cell carcinoma. Both tumors were high-grade carcinomas with extensive oncocytic (acidophilic) features. Also noted within the kidneys were cysts with atypical papillary hyperplasia. The clinicopathologic findings along with review of the literature suggest a relationship between tumor growth and calcium oxalate crystal deposition in patients undergoing hemodialysis with ACDK.     

Chromosomes in renal carcinoma with reference to intratumor heterogeneity

Cytogenetic studies of renal tumors from seven patients were performed (six renal cell carcinomas, one transitional cell carcinoma). Multiple samples were obtained from each tumor as well as one sample from normal tissue. Cultures were established after collagenase disaggregation. From five tumors, two or more cultures were available for chromosome analysis. All tumors were chromosomally abnormal, although some cultures had a normal chromosome complement. Aberrations involving chromosome 3 were seen in four tumors. Two patients had an identical marker chromosome del(3)(p14), suggesting that the breakpoint may be of significance for the development of tumors of the kidney. An extra chromosome 7 was found in four patients. In all four tumors from which two or more tumor cultures were studied, the chromosome constitution showed, besides a primary cytogenetic change, additional clonal abnormalities illustrating intratumoral heterogeneity.     

Tubulocystic carcinoma of the kidney: a new entity among renal tumors

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.