Spectrum Of Renal Cell Carcinoma Research Articles

Incorporating Stereotactic Ablative Radiotherapy into the Multidisciplinary Management of Renal Cell Carcinoma.

Stereotactic ablative radiotherapy (SABR) has challenged the conventional wisdom surrounding the radioresistance of renal cell carcinoma (RCC). In the past decade, there has been a significant accumulation of clinical data to support the safety and efficacy of SABR in RCC. Herein, we review the use of SABR across the spectrum of RCC. We performed an online search of the Pubmed database from January 1990 through April 2023. Studies of SABR/stereotactic radiosurgery targeting primary, extracranial, and intracranial metastatic RCC were included. For SABR in non-metastatic RCC, this includes its use in small renal masses, larger renal masses, and inferior vena cava tumor thrombi. In the metastatic setting, SABR can be used at diagnosis, for oligometastatic and oligoprogressive disease, and for symptomatic reasons. Notably, SABR can be used for both the primary renal tumor and metastasis-directed therapy. Management of RCC is evolving rapidly, and the role that SABR will have in this landscape is being assessed in a number of ongoing prospective clinical trials. The objective of this narrative review is to summarize the evidence corroborating the use of SABR in RCC.

The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth.

Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic “type 1 versus type 2” classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth.

Clinicopathological characterisation of renal cell carcinoma in young adults: a contemporary update and review of literature.

Renal cell carcinomas are relatively rare in children and young adults. While well characterised in adults, the morphological and molecular characterisation of these tumours in young patients is relatively lacking. The objective of this study was to explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinico-pathological, immunohistochemical and molecular characteristics by evaluating a large retrospective cohort of renal cell carcinoma patients age 30years or younger. Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at age 30years or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and tuberous sclerosis complex-associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumours in our series remained unclassified. Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histological similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. Microphthalmia-associated transcription (MiT) family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the paediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumours with further potential for future subcategories in the renal cell carcinoma classification.

Determination of the Expression of PD-L1 in the Morphologic Spectrum of Renal Cell Carcinoma.

Immunotherapy is reportedly an effective form of therapy for some advanced cancers such as lung adenocarcinoma, malignant melanoma and colorectal adenocarcinoma. In renal cell carcinoma (RCC), the role of immunotherapy is under investigation. Programmed Death-Ligand 1 (PD-L1) is a molecule expressed on the surface of certain tumor cells and binds to the Programmed cell death protein 1 (PD-1) on cytotoxic T-cells, an interaction that inhibits the antitumor immune response. The aim of this study is to evaluate PD-L1 expression in the morphologic spectrum of RCC. A total of 172 cases of RCC comprising all types were studied and the PD-L1 was correlated with immune response for CD4 and CD8. Positive membranous staining for PD-L1 was seen in 59 (34%) of the 172 samples. The positive cases were HLRCC (31/53), Type 1 Papillary RCC (10/31), Chromophobe (7/20), Hybrid (3/9), TFE-3 related cancer (3/8), Undifferentiated (3/5), and TFEB tumors (2/2).Clear cell carcinomas, Oncocytomas and SDHB deficient-RCC didn't show any expression of PD-L1; (0/34;0/7;0/3). Our results demonstrated that aggressive forms of RCC such as HLRCC have high expression of PD-L1, in contrast to clear cell renal carcinomas. Our findings support a possible role of anti-PD-L1/PD-1 immunotherapies in the treatment of PD-L1-positive RCC.

Reactivity of CK7 across the spectrum of renal cell carcinomas with clear cells.

Current available data on cytokeratin 7 (CK7) immunostaining pattern in the clear cell renal cell carcinoma (RCC) spectrum is conflicting. The aim of this study was to assess CK7 immunoreactivity within the spectrum of clear cell renal neoplasms, including clear cell RCC, multicystic renal neoplasm of low malignant potential and clear cell papillary RCC-like tumours. We analysed two clones of CK7 and two tumour blocks for a total of 75 cases divided into five distinct groups: (i) low-grade clear cell RCC, (ii) high-grade clear cell RCC, (iii) multicystic renal neoplasm of low malignant potential, (iv) clear cell RCC with cystic changes and (v) clear cell papillary RCC-like tumours. We found the highest CK7 reactivity in low-grade clear cell RCC, multicystic renal neoplasm of low malignant potential and clear cell papillary RCC-like groups, ranging from 60% to 93%. Our findings show that CK7 immunoreactivity in clear cell RCC is variable, and the extent of staining depends on the grade and architectural growth patterns of the tumours.

Morphological spectrum of renal cell carcinoma, unclassified: an analysis of 136 cases.

Renal cell carcinoma, unclassified (RCCU) is a category that includes a morphologically and biologically heterogeneous group of tumours that are unable to be diagnosed as other well-defined entities. We aim to describe the morphological findings of tumours within this category and to determine the most frequent morphological features leading to classification difficulty. One hundred and thirty-six cases of RCCU were examined. Patients ranged in age from 23 to 87years. Seventy-seven patients were men and 59 were women. International Society of Urological Pathology (ISUP) grade was most commonly 3 (n=66), followed by 2 (n=42) and 4 (n=28). Tumour size ranged from 0.6 to 24.9cm. The American Joint Committee on Cancer (AJCC) pathological T categories included pT1a (n=50), pT1b (n=14), pT2a (n=7), pT2b (n=4), pT3a (n=50) and pT4 (n=9). Forty-four cases included lymph node(s), 41% of which (n=18) had metastases. Tumours were assessed for a variety of histological features and assigned to the following morphological groups: predominantly oncocytoma/chromophobe RCC-like; clear cell RCC-like; papillary RCC-like; collecting duct-like; and pure sarcomatoid differentiation. The majority of the oncocytoma/chromophobe and clear cell RCC-like phenotypes were low stage (pT1 or pT2). The papillary RCC-like, collecting duct-like and pure sarcomatoid phenotypes were mainly high stage (pT3 or pT4). Renal cell carcinoma, unclassified is a term that encompasses tumours with a variety of morphological features and a wide biological spectrum. The most common source of diagnostic difficulty was tumours composed of predominantly eosinophilic cells.

The spectrum of renal cell carcinoma in adults.

The spectrum of renal cell carcinoma (RCC) includes many neoplasms with distinct cytogenetics, biologic behaviors, and imaging appearances. The advent of molecular therapies targeting different tumor types, new insights into the relative roles of biopsy and surveillance for small incidental tumors, and a growing array of nephron-sparing interventions have altered management of RCC. Similarly, the role of the radiologist is changing, and it is becoming increasingly important for radiologists to familiarize themselves with the various types of RCC. This article introduces the reader to the common and uncommon recognized types of renal cell carcinoma and discusses how these neoplasms differ in imaging appearance and behavior.

Can Mutations in the BAP1 Gene be Detected by Immunohisto-chemistry in Hereditary Kidney Cancers?

Background: Hereditary renal cell carcinoma (RCC) constitutes about 5% of all RCCs. The most common and well studied syndromes include, VHL, HLRCC, BHD, Familial Oncocytoma, RCC Papillary Type 1, TSC, RCC associated with Succinate dehydrogenase B (SHDB) mutations and others. Several genes, including VHL, MET, FLCN, FH and genes encoding the succinate dehydrogenase (SDH) subunits B/C/D have been identified as causative. However, the genetic basis of a significant percentage of familial RCC, some with clear cell morphology remain unknown. BAP1 (BRCA1 associated protein-1), a tumor suppressor gene that encodes a nuclear deubiquitinase, is inactivated in 15% of sporadic clear cell RCCs and its loss was associated with high tumor grade and poor prognosis. In this study, we investigated the possible role of this gene in the spectrum of RCC part of hereditary syndromes. Materials and Methods: To elucidate the role of BAP1 in all the spectrum of hereditary RCC, we studied by IHC a panel of RCCs which covers the spectrum of kidney cancers and included 10 VHL tumors, 6 HLRCCs, 8 chromophobe, 5 Hereditary Papillary Type 1, 6 Oncocytomas, 3 BHD (hybrid), and 24 sporadic clear cell RCCs. To analyze the BAP1 expression in these tumors, formalin fixed paraffin embedded (FFPE) tissues were immunostained with mouse monoclonal anti-human BAP1 antibody (Clone C-4, Santa Cruz). Results: We found that all the tumors except two showed positive nuclear staining for BAP1. The two negative cases that were negative for BAP1 were Clear cell type and belonged to two siblings. Molecular analysis in a prepublished study showed both patients harboring the p.L14H mutation. Conclusion: Our study supports the hypothesis that BAP1 mutations can play a role in hereditary syndromes predominantly in clear cell tumors. Staining for BAP1 should be done when there is no definite known mutation in a clear cell cancer but the patient gives history of familial kidney cancer. The two related patients who had similar mutations had aggressive, metastatic disease, which suggests that probably BAP1 does play a role in hereditary RCC clear cell type.

Clear Cell Papillary Renal Cell Carcinoma: A Rare Subtype

Introduction: Renal cell carcinoma (RCC) is generally divided into clear cell, papillary, and chromophobe subtypes. Clear cell papillary RCC is a recently described subtype. Case report: We report the case of a 42 year old female who was found on computed tomography scan of the abdomen to have a cyst which appeared to involve the right kidney. Pathology of the cyst wall revealed features consistent with a RCC, clear cell papillary type. Discussion: Clear cell papillary RCC are a recently described entity with less than 100 cases reported in the literature. Most cases in the literature have been associated with end-stage renal disease, however more case are being reported in patients without renal disease. Conclusion: Clear cell papillary RCC is a rare distinct entity in the spectrum of renal cell carcinoma. Based on the literature they appear to be clinically indolent tumors; however, more research is required to further characterize and prognosticate these rare tumors.

Expression Analysis of Wnt-5a in Renal Epithelial Neoplasms: Distinguishing Renal Oncocytoma from a Wide Spectrum of Renal Cell Carcinomas

To study the expression of a novel marker, Wnt-5a, in renal epithelial neoplasms and determine its clinicopathological significance. Immunohistochemical analysis of Wnt-5a was carried out in normal human kidney samples as well as in 123 primary renal epithelial neoplasms including 37 clear cell renal cell carcinomas (RCCs), 24 papillary RCCs (15 type 1 and 9 type 2), 25 chromophobe RCCs, 11 Xp11 translocation carcinomas, 6 mucinous tubular and spindle cell carcinomas, and 20 oncocytomas. Wnt-5a was expressed in 18.9% (7/37) of clear cell RCCs, 12.5% (3/24) of papillary RCCs, 16% (4/25) of chromophobe RCCs, 18.2% (2/11) of Xp11 translocation carcinomas, 0% (0/6) of mucinous tubular and spindle cell carcinomas, and 100% (20/20) of oncocytomas. There was a significant difference in Wnt-5a immunohistochemistry between renal oncocytoma and the other subtypes of RCC (P < 0.01). Our results indicate that Wnt-5a is a potentially useful immunohistochemical marker for the complex differential diagnosis between oncocytoma and other subtypes of RCC and also suggest that Wnt-5a may be a tumor suppressor gene in RCC.

Protein expression profiling in the spectrum of renal cell carcinomas.

In this study, we aimed to evaluate the protein expression profile of a spectrum of renal cell carcinomas (RCC) to find potential biomarkers for disease onset and progression and therefore, prospective therapeutic targets. A 2D-gel based proteomic analysis was used to outline differences in protein levels among different subtypes of renal cell carcinomas, including clear cell carcinomas, papillary lesions, chromophobe tumors and renal oncocytomas. Spot pattern was compared to the corresponding normal kidney from the same patients and distinctive, differentially expressed proteins were characterized by mass spectrometry. Twenty-one protein spots were found differentially expressed between clear cell RCC and normal tissue and 38 spots were found expressed in chromophobe tumors. Eleven proteins were identified, with most differentially expressed -by fold change- between clear cell tumors and the corresponding normal tissue. Two of the identified proteins, Triosephosphate isomerase 1 (TPI-1) and Heat Shock protein 27 (Hsp27), were further validated in a separate set of tumors by immunohistochemistry and expression levels were correlated with clinicopathologic features of the patients. Hsp27 was highly expressed in 82% of the tumors used for validation, and all cases showed strong immunoreactivity for TPI-1. In both Hsp27 and TPI-1, protein expression positively correlated with histologic features of the disease. Our results suggest that the subjacent cytogenetic abnormalities seen in different histological types of RCC are followed by specific changes in protein expression. From these changes, Hsp27 and TPI-1 emerged as potential candidates for the differentiation and prognosis in RCC.

Broadening Spectrum of Renal Cell Carcinoma in Children and Young Adults

Broadening Spectrum of Renal Cell Carcinoma in Children and Young Adults

Bellini duct carcinoma: further evidence for this rare variant of renal cell carcinoma

Bellini duct carcinomas have recently been identified as a new entity in the spectrum of renal cell carcinomas and 10 cases have now been reported. The present paper adds detailed clinical and morphological data on six new cases. In addition, immunohistological and electronmicroscopical results support the origin of these tumours from the renal collecting ducts, especially the papillary ducts (Bellini ducts). A set of immunohistological reactions, including reactions to cytokeratins 13 and 19, vimentin and UEA-1 was found to facilitate the differential diagnosis of Bellini duct carcinomas from other renal cell carcinomas and infiltrating urothelial carcinomas of renal pelvis.