Feasibility of using CT radiomic signatures for predicting CD8-T cell infiltration and PD-L1 expression in renal cell carcinoma.

Objectives: To identify computed tomography (CT)-based radiomic signatures of cluster of differentiation 8 (CD8)-T cell infiltration and programmed cell death ligand 1 (PD-L1) expression levels in patients with clear-cell renal cell carcinoma (ccRCC). Methods: Seventy-eight patients with pathologically confirmed localized ccRCC, preoperative multiphase CT and tumor resection specimens were enrolled in this retrospective study. Regions of interest (ROI) of the ccRCC volume were manually segmented from the CT images and processed using a radiomics panel comprising of 1708 metrics. The extracted metrics were used as inputs to three machine learning classifiers: Random Forest, AdaBoost, and ElasticNet to create radiomic signatures for CD8-T cell infiltration and PD-L1 expression, respectively. Results: Using a cut-off of 80 lymphocytes per high power field, 59 % were classified to CD8 highly infiltrated tumors and 41 % were CD8 non highly infiltrated tumors, respectively. An ElasticNet classifier discriminated between these two groups of CD8-T cells with an AUC of 0.68 (95 % CI, 0.55-0.80). In addition, based on tumor proportion score with a cut-off of > 1 % tumor cells expressing PD-L1, 76 % were PD-L1 positive and 24 % were PD-L1 negative. An Adaboost classifier discriminated between PD-L1 positive and PD-L1 negative tumors with an AUC of 0.8 95 % CI: (0.66, 0.95). 3D radiomics metrics of graylevel co-occurrence matrix (GLCM) and graylevel run-length matrix (GLRLM) metrics drove the performance for CD8-Tcell and PD-L1 classification, respectively. Conclusions: CT-radiomic signatures can differentiate tumors with high CD8-T cell infiltration with moderate accuracy and positive PD-L1 expression with good accuracy in ccRCC.

Co-existence of ESC-RCC, EVT, and LOT as synchronous and metachronous tumors in six patients with multifocal neoplasia but without clinical features of tuberous sclerosis complex.

Renal cell tumors with oncocytic phenotypes represent a daily challenge, with several novel, emerging, and provisional entities enriching the diagnostic repertoire. Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), low-grade oncocytic tumor (LOT), and eosinophilic vacuolated tumor (EVT) have been recognized as unique entities, although their distinctive nature remains controversial. Although most of these tumors are sporadic, rare reports of similar tumors in tuberous sclerosis complex (TSC) have been published. We describe multifocal, often bilateral, tumors in six patients without personal or family history of syndromic diseases. More than 60 tumors in various combinations were identified in 10 nephrectomies and one biopsy encompassing ESC-RCC (n = 6), LOT (n = 14), EVT (n = 1), clear cell RCC with fibromyomatous stroma (n = 12), clear cell RCC (n = 2), angiomyolipomas (AMLs; n > 20), unclassified renal cell tumors (n = 2), papillary adenomas (n = 4), and renomedullary interstitial cell tumor (n = 1). TSC1 germline pathogenic mutations were confirmed in two patients. A tumor without germline testing in a third patient revealed TSC1 biallelic inactivation. Two additional patients had molecular testing, which excluded common renal mutations and syndromes. We provide the first evidence of co-existence in the same organ and unequivocal relatedness of ESC-RCC, EVT, and LOT. End-stage renal disease was present in three of six patients with precursor lesions to all above tumors within adjacent renal parenchyma. In conclusion, identification of multifocal tumors with TSC-like morphology, especially in association with AMLs, could be the first manifestation of clinically silent TSC guiding clinical recommendations for further genetic testing and/or treatment recommendations.

Novas entidades em neoplasias renais / New entities in renal neoplasms

Introdução: As últimas classificações das neoplasias renais da Organização Mundial da Saúde (OMS), incluindo a mais recente de 2016, adicionaram algumas entidades diagnósticas às neoplasias primárias renais, além das tradicionalmente mais conhecidas. A presente revisão aborda seis das mais frequentes destas neoplasias mais recentemente descritas. Métodos: Revisão bibliográfica enfatizando os aspectos clínicos, histopatológicos, imuno-histoquímicos e moleculares das neoplasias recentemente adicionadas à classificação de neoplasias renais da OMS. Resultados: Dentre as novas entidades diagnósticas, destacam-se: neoplasia renal cística multilocular de baixo potencial de malignidade, carcinoma de células renais de translocação associada ao fator de transcrição da microftalmia (MIT), carcinoma de células renais deficiente de succinato-desidrogenase (SDH), carcinoma fusocelular e tubular mucinoso, carcinoma de células renais papilar de células claras e carcinoma de células renais não classificado. Conclusão: A adequada classificação das neoplasias renais é de extrema importância para a definição de condutas terapêuticas e para a avaliação prognóstica. Ressalta-se o necessário conhecimento de neoplasias recentemente descritas, particularmente em seus aspectos clínico, histopatológico imuno-histoquímico e molecular.

Introduction: The last edition of World Health Organization (WHO) on kidney neoplasms, including the 2016 version has added new diagnostic entities to the list of primary kidney tumors. This review sough to describe the more frequent recently described histopathologic entities. Methods: Literature review emphasizing clinicopathologic characteristics, immunohistochemistry, and molecular profile of recently added kidney neoplasms included in the 2016 WHO classification. Results: Among the new diagnostic entities, the six highlighted are: multilocular cystic renal neoplasm of low malignant potential, translocation renal cell carcinoma associated with the transcription factor of microphthalmia (MIT), succinate dehydrogenase-deficient renal cell carcinoma, tubulocystic renal cell carcinoma, clear cell papillary renal cell carcinoma, and unclassified renal cell carcinoma. Conclusion: The proper classification of the tumors of the kidney is critical for management of patients and prognosis evaluation. It is necessary to emphasize the importance of the knowledge of the newly described neoplasms, especially clinical aspects, histopathology, immunohistochemistry, and molecular pathology.

The expression and significance of COX-2 and VEGF in clear renal cell carcinoma / 中国医师杂志

Objective To study the correlation between vascular endothelial growth factor(VEGF) and cyclooxygenase-2 (COX-2) in clear renal cell carcinoma (CRCC).Methods In 60 cases of CRCC and 10 cases of normal renal tissue,immunohistochemistry was used to examine the expression of COX-2 and VEGF.Results The positive expression rate of COX-2 in CRCC (76.7％) was significantly higher than that in normal renal tissue (20％) (x2 =10.28,P ＜0.01).The positive expression rate of VEGF in CRCC(73.3％) was significantly higher than that in normal renal tissue (20％) (x2 =8.58,P ＜0.01).The expressions of COX-2 and VEGF in CRCC were correlated with each other (r =0.469,P ＜0.01).Conclusions The expressions of COX-2 and VEGF were involved in the pathophysiolical processes of clear renal cell carcinoma.The expression levels of COX-2 and VEGF might be used to evaluate the development of clear renal cell carcinoma.