Showing papers on "Papillary renal cell carcinomas published in 2013"
TL;DR: Higher c-Met expression was detected in all RCC subtypes than in the adjacent normal renal tissue, and Expression was highest in papillary and sarcomatoid subtypes, and high-grade and stage tumors.
149 citations
TL;DR: In this article, the authors show that mutations in NRF2, CUL3, and SIRT1 are responsible for driving the activation phenotype in sporadic PRCC2 transcriptome sequencing.
Abstract: Sustained activation of the stress-regulated transcription factor NRF2 (NFE2L2) is a prominent feature of many types of cancer, implying that mutations driving NRF2 may be important to tumor progression In hereditary type 2 papillary renal cell carcinoma (PRCC2, also known as hereditary leiomyomatosis and renal cell cancer), NRF2 activation is a direct consequence of the accumulation of intracellular fumarate, a result of fumarate hydratase (FH) inactivation, but it is not clear how NRF2 may be activated in sporadic forms of PRCC2 Here we show that somatic mutations in NRF2, CUL3, and SIRT1 are responsible for driving the NRF2 activation phenotype in sporadic PRCC2 Transcriptome sequencing revealed the expression pattern of mutant alleles of NRF2, CUL3, and SIRT1 and also confirmed NRF2 activation in clinical specimens Our results show a convergence in somatic mutations in sporadic PRCC2 with FH mutation in hereditary PRCC2
141 citations
TL;DR: Nearly one third of papillary RCCs in the patient population had atypical features at histology, and on CT and MRI, there are some significant differences in imaging features between type 1 and type 2 tumors; however, substantial overlap precludes categorization on a per-patient basis.
Abstract: OBJECTIVE. The objective of our study was to determine the frequency of atypical papillary renal cell carcinomas (RCCs) and identify imaging differences between type 1 and type 2 papillary RCCs once atypical papillary RCC tumors have been excluded. MATERIALS AND METHODS. Eighty-two papillary RCC tumors were classified at pathology as type 1, type 2, or atypical. The CT and MRI examinations of these tumors were reviewed. Imaging features such as tumor size, margins, heterogeneity, and enhancement were assessed and the findings in type 1 and type 2 tumors were compared. RESULTS. There were 43 type 1 and 13 type 2 tumors. Atypical histologic features (i.e., tumors containing both type 1 and type 2 components, clear cells, or components with atypically high nuclear grade [in type 1 tumors] or low nuclear grade [in type 2 tumors]) were seen in 26 tumors. On CT, type 2 tumors more commonly had infiltrative margins (p = 0.05) and were more likely to have calcifications (p = 0.04) than type 1 tumors, although the...
122 citations
TL;DR: Branched tubules, small papillae, and the immunohistochemical and molecular profiles aid in distinguishing these tumors from clear cell renal cell carcinoma and multilocular cystic renal cell cancer.
122 citations
TL;DR: The available data suggest that treatments currently approved for RCC are active in ncc subtypes, although the overall clinical benefit may be less than for clear cell RCC.
62 citations
TL;DR: To date no patient has had adrenal malignancy, and active surveillance of hereditary leiomyomatosis and renal cell carcinoma adrenal nodules appears justified.
60 citations
TL;DR: The results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling and microRNAs are able to accurately classify RCC samples, indicating that Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC.
Abstract: Besides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes. We performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes. Only five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes. MicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling.
56 citations
TL;DR: The case of a 68-year-old male with extension of papillary renal cell carcinoma (Fuhrman grade III) along a percutanous biopsy tract detected at the time of partial nephrectomy is reported.
Abstract: We report the case of a 68-year-old male with extension of papillary renal cell carcinoma (Fuhrman grade III) along a percutanous biopsy tract detected at the time of partial nephrectomy. Biopsy was performed to a obtain tissue diagnosis of a complex renal cyst as the patient was unable to receive intravenous contrast for imaging due to a severe allergy. Although biopsy of indeterminate renal lesions can provide valuable diagnostic information, there are inherent risks associated with this procedure. The rare occurrence of tumour seeding should be considered when recommending percutaneous biopsy to a patient with a renal mass.
54 citations
TL;DR: To evaluate morphological and immunohistochemical features helpful in distinguishing metanephric adenoma (MA) from solid papillary renal cell carcinoma (s‐PRCC).
Abstract: Aims
To evaluate morphological and immunohistochemical (IHC) features helpful in distinguishing metanephric adenoma (MA) from solid papillary renal cell carcinoma (s-PRCC).
Methods and results
We present a detailed study of 21 MA and 23 s-PRCC. The two entities exhibited significant similarities, both being well-circumscribed tumours composed of tightly packed small cells arranged in solid sheets or ill-defined tubules, often presenting glomeruloid bodies, psammoma bodies and dystrophic calcification, and showing overlapping immunoreactivity for S100, CD57 and CK7. Conversely, most MA were non-encapsulated, whereas most s-PRCC showed a thick fibrous pseudocapsule; MA cells had scanty cytoplasm and a high nuclear:cytoplasmic ratio in comparison to s-PRCC, where occasional tumour cells showed abundant cytoplasm and high nuclear grade. Polypoid branching fronds were common in MA, but absent in s-PRCC; multifocality and papillary hyperplasia/adenoma were seen only in s-PRCC. MA were positive for WT1 and negative for EMA and alpha-methylacyl-CoA racemase (AMACR); s-PRCC were positive for EMA and AMACR and negative for WT1.
Conclusions
Despite overlapping features, careful morphological and architectural evaluation should result in accurate diagnosis of most MA and s-PRCC. In challenging cases, IHC stains for WT1, EMA and AMACR may help in distinguishing these two entities.
54 citations
TL;DR: The spectrum of primary renal tumors in which clear cells may appear is revisited and many of the genetic disorders underlying this disease are also present in sporadic, conventional renal cell clear cell carcinomas.
Abstract: The spectrum of primary renal tumors in which clear cells may appear is revisited in this review. The pathologist's viewpoint of this topic is pertinent because not all the tumors with clear cells are carcinomas and not all renal cell carcinomas with clear cells are clear cell renal cell carcinomas. In fact, some of them are distinct entities according to the new WHO classification. The morphological approach is combined with genetics. Renal cell carcinoma related to von Hippel–Lindau disease is reviewed first because many of the genetic disorders underlying this disease are also present in sporadic, conventional renal cell clear cell carcinomas. Subsequently, conventional renal cell clear cell carcinomas, familial, non von Hippel–Lindau-associated renal cell carcinomas, translocation carcinomas, hereditary papillary renal cell carcinomas, carcinomas associated to tuberous sclerosis and to Birt–Hogg–Dube syndrome, chromophobe renal cell carcinomas, carcinomas associated with end-stage renal disease, and clear cell tubulopapillary carcinomas are reviewed. Finally, epithelioid angiomyolipoma is also considered in this review.
49 citations
TL;DR: Fluorescence in situ hybridization studies results showed some features overlapping with papillary renal cell carcinoma in both the tubulocystic and collecting duct-like components and with 1 exception showed identical cytogenetic findings between the 2 components.
TL;DR: A cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors is presented.
25 May 2013
TL;DR: Laroscopic removal of adrenal metastasis is minimally invasive and oncologically effective and the final outcome of patients mainly depends on the primary tumor histology and on the chances of treatment of metastases subsequently developed.
Abstract: Purpose: To report oncological outcome of laparoscopic treatment of metastases to the adrenal gland Patients and Methods: We retrospectively reviewed a prospectively maintained database to evaluate the outcome of 16 patients undergone laparoscopic adrenalectomy (LA) for adrenal metastasis. Preoperative data, perioperative results and follow-up were evaluated. Results: Nineteen LAs were performed in 17 patients. Pathologic analysis revealed renal cell carcinoma metastases in 11 patients and transitional cell carcinoma metastases in 2 men who underwent bilateral laparoscopic adrenalectomy. Metastasis from papillary renal cell carcinoma, poorly differentiate lung carcinoma, colorectal carcinoma and melanoma were respectively detected in the other four patients. Surgical margins were negative in all patients and local recurrence occurred in one patient. At a median follow-up of 21 months 12 patients were alive and 5 were disease free. Five out of 11 patients with metastatic renal cell carcinoma were recurrence free and 10 alive. Indeed no patients with primary tumor histology different by renal cell carcinoma was recurrence free and 4 out of those 5 five patients died of disease. Conclusion: Laparoscopic removal of adrenal metastasis is minimally invasive and oncologically effective. The final outcome of patients mainly depends on the primary tumor histology and on the chances of treatment of metastases subsequently developed.
TL;DR: The measurement of the degree of enhancement on contrast-enhanced multidetector CT may be a simple and useful method to radiologically differentiate between the two histological types of RCC.
Abstract: PURPOSE Conventional clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) have different behavioral characteristics and clinical management strategies (nephrectomy vs. nephron-sparing surgery). Our aim was to retrospectively evaluate the contrast enhancement pattern of ccRCC and pRCC and evaluate its possible diagnostic role for preoperative differentiation using a standardized protocol. MATERIALS AND METHODS Quadriphasic multidetector computed tomography (CT) images (unenhanced, corticomedullary, nephrographic, and excretory phases) of 19 patients with 20 ccRCC and 14 patients with 15 pRCC lesions (mean ages, 62.3±14.1 and 61.4±13.7 years, respectively) were reviewed retrospectively. The attenuation characteristics were compared with the attenuation of the normal renal cortex using either multiple 10 mm2 regions of interest or whole tumor attenuation measurements. The degree of contrast enhancement was also compared. RESULTS Univariate analysis revealed that ccRCC lesions showed higher mean attenuation values on the corticomedullary and nephrographic phases compared with pRCC masses (P < 0.05) using both measurement techniques. CONCLUSION The findings underscore the importance of multiphase CT in the differentiation of these two subtypes of RCC using standard assessment techniques. The measurement of the degree of enhancement on contrast-enhanced multidetector CT may be a simple and useful method to radiologically differentiate between the two histological types of RCC.
TL;DR: The prevailing theories regarding kidney regeneration are presented, since a better understanding of this process might be of relevance when considering the different malignancies that arise from kidney epithelium.
TL;DR: Panel of carbonic anhydrase IX, galectin-3, CK7, and α-methylacyl coenzyme a racemase is sensitive and specific for the differential diagnosis of the renal epithelial tumors.
TL;DR: Infiltrative MRI appearance and renal vein thrombus identify a subset of pathological type 2 pRCC at a significantly increased risk of metastatic disease.
Abstract: Objective
To evaluate the prognostic implications of the MRI appearance and pathological features of papillary renal cell carcinoma (pRCC).
TL;DR: A patient with MET-mutated papillary RCC that responded to MET inhibition with a small molecule kinase inhibitor, PF-04217903, for 26 months is described.
Abstract: Introduction Papillary renal cell carcinoma (RCC) is the most prevalent nonclear cell histologic subtype of renal carcinoma and constitutes approximately 10% of renal cancers, affecting 5,400 patients per year in the United States. Activating MET mutations are present in the majority of hereditary papillary RCCs and up to 13% of sporadic papillary RCCs. Here we describe a patient with MET-mutated papillary RCC that responded to MET inhibition with a small molecule kinase inhibitor, PF-04217903, for 26 months. At the time of acquired resistance to treatment, we identified a genomic duplication that encompassed the mutated kinase domain of MET.
Journal Article•
TL;DR: The results suggest that OPRCC shows distinct morphology, indolent clinical behavior, and similar immunohistochemical and cytogenetic features with PRCC, seems to be a variant in the PRCC group.
Abstract: Papillary renal cell carcinoma (PRCC) is traditionally classified into type 1 and type 2. Recently, an oncocytic variant of PRCC has been described. We report a series of 6 oncocytic renal papillary tumors (OPRCC) which tended to occur in older patients (mean, 56.8 years) with a male preference (male-to-female ratio is 5:1). All 6 patients are alive with no evidence of disease after initial resection, showing an indolent clinical behavior. Histologically, tumors exhibited predominant papillary structure with delicate fibrovascular cores. Papillae were lined by single layers of cells with large, deeply eosinophilic and finely granular cytoplasms and round regular nucleus. The phagocytosis of tumor cells was frequently and evidently seen in our cases that hemosiderin-laden tumor cells and foamy tumor cells were noticed in five and four cases respectively. All tumors were immunoreactive for racemase, vimentin, CD10, and MET and negative for CD117. While E-cadherin, EMA, and cytokeratin 7 exhibited variable immunopositivity. FISH analysis was performed in five of six cases and found heterogeneous results. Trisomy of chromosomes 7 was found in three cases and trisomy of chromosomes 17 in two cases. Loss of chromosome Y was noted in one of four tumors in male patients. MET gene status was also investigated by direct sequencing in all 6 cases and found no distinct mutation in any case. These results suggest that OPRCC shows distinct morphology, indolent clinical behavior, and similar immunohistochemical and cytogenetic features with PRCC, seems to be a variant in the PRCC group. Whether the strong expression of MET indicates a potential therapeutic target is still unknown and requires further investigation in clinical trials.
TL;DR: The present study shows that KIM-1-expression promotes tumorigenesis primarily by directly conferring oncogenic properties to renal epithelial cells by resulting in production of a variety of chemokines and cytokines that support tumor progression and angiogenesis.
Abstract: Background. Renal cell carcinoma (RCC) is characterized by lack of early warning signs, diverse clinical manifestations, absence of a reliable diagnostic and predictive biomarker, and resistance to targeted therapy. Thus, novel approaches for diagnosis, management and treatment of RCC are urgently needed. Kidney Injury Molecule-1 (KIM-1) is not expressed in normal kidney tissues but markedly up-regulated in dedifferentiated proximal tubular epithelial cells following renal injury. We demonstrated that KIM-1 is expressed ubiquitoulsy by both primary and metastatic lesions of clear cell and papillary renal cell carcinoma, while barely detectable in other subtypes of RCC. Additionally, the ectodomain of KIM-1 is cleaved by matrix metalloproteinases and sheds into the surrounding milieu. Methods. KIM-1 was stably transfected in immortalized renal tubular epithelial cells (LLC-PK1, gain-of-function) and KIM-1 was downmodulated in RCC cell lines (loss-of-function) using a siRNA lentiviral approach. KIM-1 function was assessed using these two systems. Results. Stable expression of KIM-1 in non-malignant renal epithelial cells increased cell proliferation, migration and invasion potential, induced anchorage independent growth, and increased the secretion of tumor promoting and angiogenic factors including VEGF, Ang2, TGF beta and IL-6 (PK1-KIM-1); while depletion of KIM-1 in RCC cells led to G1 cell cycle arrest phase and senescence. Recently, we and others have demonstrated that KIM-1 is a phosphatildyl serine receptor and the expression of KIM-1 converts a normal epithelial cell into a “semi professional phagocyte” and facilitates the removal of apoptotic and necrotic cells by recognizing phosphotidyl serine (PS) on their cell surface. Our data suggests that during this process, tumor epithelial cells undergo reprogramming and secrete and activate cytokines involved in cell survival and angiogenesis programs. Conclusions. The present study shows that KIM-1-expression promotes tumorigenesis primarily by two distinct mechanisms: i) by directly conferring oncogenic properties to renal epithelial cells; ii) by resulting in production of a variety of chemokines and cytokines that support tumor progression and angiogenesis. We believe that our findings can significantly contribute to the development of novel therapeutic apporaches and in the advancement of management strategies in RCC and help reduce associated mortality and morbidity. Citation Format: Venkata Sabbisetti, Rupal Bhatt, Swetha Ramadesikan, Joseph Bonventre. Kidney injury molecule-1: a novel therapeutic target in renal cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5195. doi:10.1158/1538-7445.AM2013-5195 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
TL;DR: A patient who developed more than 20 BM plus multiple bone, lymph node, and soft tissue metastases roughly one decade after removal of the primary tumor, and who remarkably survived 23 months is presented.
Abstract: Introduction Renal cell carcinoma (RCC) accounts for 80% to 85% of primary neoplasms that arise in the kidney, with an estimated 65,000 new cases and 13,500 deaths each year in the United States. Papillary RCC (PRCC) is the second most common type of RCC with a 5:1 male predominance. PRCC is classified into two groups; type 2 tumors are high grade and associated with a poor prognosis. The prevalence of brain metastases (BM) from RCC ranges from 6% to 10%, and the reported median survival time is 5 months for patients who are treated with whole-brain radiotherapy (WBRT) alone. We present a patient who developed more than 20 BM plus multiple bone, lymph node, and soft tissue metastases roughly one decade after removal of the primary tumor, and who remarkably survived 23 months.
TL;DR: The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis, and CT may help to differentiate with papillary renal cell carcinoma.
Abstract: Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited. In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K. A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis. The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249
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TL;DR: To investigate the impact of histological subtypes on the survival of patients presenting with renal cell carcinoma extending into the inferior vena cava, a large number of patients with this disease have suffered from atypical central giant cell granuloma.
Abstract: Objectives
To investigate the impact of histological subtypes on the survival of patients presenting with renal cell carcinoma extending into the inferior vena cava.
Methods
From January 1985 until October 2011, 68 patients with renal cell carcinoma extending into the inferior vena cava underwent radical nephrectomy and inferior vena cava thrombectomy at Tokyo Women's Medical University, Tokyo, Japan. Their clinical and pathological parameters were reviewed from the medical charts.
Results
The median follow up was 19 months (range 0.1–144 months). The tumor thrombus level was I in four patients (6%), II in 38 patients (56%), III in 12 patients (18%) and IV in 14 patients (20%). Papillary histological subtype was found in seven patients (10%), and clear cell in 61 patients (90%). Patients with a papillary subtype had a significantly worse survival outcome than the patients with the clear cell subtype (median survival time 9.0 vs 36.1 months, P < 0.001). Multivariate analysis also showed that the papillary subtype was the only independent prognostic factor for unfavorable cancer-specific survival (P = 0.03). When the patients presented with metastases to lymph nodes or distant metastases, the median survival of the patients with a papillary subtype was extremely short, at just 5.2 months compared with those with a clear cell subtype (24.0 months, P = 0.001).
Conclusions
Patients with renal cell carcinoma extending into the inferior vena cava with a papillary subtype show a considerably shorter survival compared with those with a clear cell subtype. The papillary renal cell carcinoma extending into the inferior vena cava patient might be an inappropriate candidate for extensive surgery when metastases to nodes or distant organs are found.
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TL;DR: Newer radiographic techniques, including ultrasonography, computed tomography, and magnetic resonance imaging, are detecting kidney tumors more frequently and at a lower disease stage, when tumors can be resected for cure.
Abstract: Renal cell cancer (RCC) is a heterogeneous disease and consists of subsets originating from cells of different parts of the renal tubulus. Recent genetic studies have demonstrated that specific genetic abnormalities correlate with different types of RCC and could have diagnostic and prognostic consequences. Advances in molecular therapeutics offer hope for novel treatment options for patients with (advanced) disease.
TL;DR: The incidence of kidney cancer is gradually increasing, with a rate of 2-3% per decade, and some of the subtypes seem to form families based on morphological transition, immunohistochemical features and gene expression profile.
Abstract: The incidence of kidney cancer is gradually increasing, with a rate of 2-3% per decade. The kidney develops various kinds of neoplasms, some of which are associated with familial cancer syndromes. Such cases have provided clues to identify the cancer-responsible genes. In 2004, the World Health Organization published a new classification system of renal neoplasms, incorporating recent knowledge obtained in the cytogenetic and molecular biological fields, i.e. genes responsible for each histologic subtype (von Hippel-Lindau for clear cell renal cell carcinoma, c-met for papillary renal cell carcinoma type 1, etc.). Subsequently, the Japanese classification system in 'the General Rule for Clinicopathological Study of Renal Cell Carcinoma' has been revised as the 4th edition, according to the World Health Organization system. Several novel subtypes have been introduced, i.e. mucinous tubular and spindle cell carcinoma, and Xp11.2/TFE3 translocation-associated renal cell carcinoma. Even after the publication of the classification, other novel subtypes have emerged, i.e. acquired cystic disease-associated renal cell carcinoma and tubulocystic renal cell carcinoma. Additionally, some of the subtypes seem to form families based on morphological transition, immunohistochemical features and gene expression profile. In future, the classification of renal cell carcinoma should be reorganized on the basis of molecular biological characteristics to establish personalized therapeutic strategies.
TL;DR: To the best of the knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy.
Abstract: Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed. Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.
TL;DR: The need for radiologists to maintain caution when diagnosing renal angiomyolipomas on the basis of macroscopic fat is highlighted and the current literature on fat-containing renal masses is reviewed.
Abstract: Renal masses found to contain macroscopic fatty elements on CT or MRI imaging can generally be classified as benign angiomyolipomas. Rarely, renal cell carcinomas may also contain evidence of macroscopic fat. When true adipocytic elements are present, this is generally due to a process of osseous metaplasia in which both fat cells and calcification are co-localized within the mass. We present a patient with a large papillary renal cell carcinoma containing abundant fat with sparse, punctate calcification remote from the fatty elements on imaging. This report highlights the need for radiologists to maintain caution when diagnosing renal angiomyolipomas on the basis of macroscopic fat and reviews the current literature on fat-containing renal masses.
TL;DR: This case raises the point that renal oncocytomas can contain a hidden malignant tumour in a 68-year-old male investigated for the abdominal symptoms associated with cholelithiasis, and the small size of the RCC and the old age of the patients.
Abstract: An asymptomatic 1-cm large papillary renal cell carcinoma (RCC) embedded in a 3.5-cm large oncocytoma was diagnosed and removed by right nephrectomy in a 68-year-old male investigated for the abdominal symptoms associated with cholelithiasis. The papillary RCC displayed positive immunohistochemical stainings with cytokeratin 7, alpha-methylacyl-CoA racemase and vimentin and was negative for the E-cadherin and CD117 immunostains, whereas the oncocytoma part showed opposite staining patterns. No gains of chromosomes 7 and 17 or loss of chromosome Y was detected in the papillary carcinoma by fluorescent in situ hybridization with centromeric enumeration probes. This finding is in keeping with the morphologic diagnosis of type 2 papillary RCC reported to have lower rates of these characteristic chromosomal changes. The combination of papillary RCC and oncocytoma, two tumours of different postulated origin, is extremely rare. It may represent a simple coincidence, but 2 previous cases and our current one share a few features, including the intimate embedment of the papillary RCC in the oncocytoma, the small size of the RCC and the old age of the patients. This case raises the point that renal oncocytomas can contain a hidden malignant tumour.
Journal Article•
TL;DR: Despite its use as the sixth-line systematic treatment, the mTOR inhibitor everolimus exhibited a relatively long-term effect as compared with the previously used tyrosine kinase inhibitors and in contrast to the results in the RECORD-1 clinical trial.
Abstract: A 56-year-old man was referred to our clinic because of left lumbar pain and a left solitary renal tumor (9. 8 cm in diameter) and bilateral pulmonary metastases detected by computed tomographic scan. Pathologic diagnosis following open radical nephrectomy was papillary renal cell carcinoma, G2, pT2aN0M1. Subsequently, the patient was sequentially treated with interleukin-2 (3 months (mo), progressive disease (PD)), interferon-alpha (3 mo, PD), and oral S-1 as a clinical trial (28 mo, PD). Because of skin fibrofolliculomas, pulmonary cysts, and spontaneous pneumothorax history, Birt-Hogg-Dube (BHD) syndrome was suspected during the treatment course, despite his having no family history of the disease. Subsequent genetic testing revealed a FLCN germline mutation (c. 1285dupC). He was started on molecular-targeting therapies sequentially, i.e., sorafenib (1 mo, PD), sunitinib (4 mo, PD), and everolimus (7 mo, PD). The patient died of progressive disease at 78 mo from the initial nephrectomy and 30 mo from the start of targeted agents. Loss of FLCN function has been shown to result in the upregulation of the PI3K/mTORC1 pathway in both in vitro experiments and in vivo FLCN knockout mice models. Despite its use as the sixth-line systematic treatment, the mTOR inhibitor everolimus exhibited a relatively long-term effect as compared with the previously used tyrosine kinase inhibitors and in contrast to the results in the RECORD-1 clinical trial. This finding may provide insight into the molecular mechanism of BHDassociated renal tumors.
TL;DR: The aims of this study were to determine H NF1β expression in renal neoplasms and the potential of HNF1β as a diagnostic marker for ChRCC.
Abstract: Aims
Chromophobe renal cell carcinoma (ChRCC) is an uncommon malignant renal neoplasm with a generally indolent clinical behaviour. Previous studies revealed biallelic inactivation of the hepatocyte nuclear factor-1β (HNF1β) gene in several patients with ChRCC. The aims of this study were to determine HNF1β expression in renal neoplasms and the potential of HNF1β as a diagnostic marker for ChRCC.
Methods and results
We performed immunohistochemical staining of 79 samples taken from patients with primary renal neoplasm [19 renal oncocytomas, 18 ChRCCs, 24 clear cell renal cell carcinomas (CCRCCs), and 18 papillary renal cell carcinomas]. HNF1β was underexpressed in 16 of 18 cases of ChRCC (88.9%). By contrast, HNF1β expression was preserved in the majority of renal oncocytoma (94.7%, 18/19) and CCRCC (95.8%, 23/24) cases. The combined use of HNF1β and cytokeratin 7 (CK7) further increased the diagnostic sensitivity and specificity; the profile of HNF1β positivity and CK7 negativity was not visible in any ChRCC sample, but was common in both renal oncocytoma (94.7%, 18/19) and CCRCC (91.7%, 22/24) samples.
Conclusions
The results suggest that a lack of HNF1β expression might play an important role in the pathogenesis of ChRCC, and may serve as a good diagnostic marker for this neoplasm.