Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.
Humans ; Kidney Neoplasms/pathology* ; Carcinoma, Renal Cell/pathology* ; Diagnosis, Differential ; Angiomyolipoma/diagnosis* ; Biomarkers, Tumor/metabolism* ; Leukemia, Myeloid, Acute/diagnosis* ; Membrane Glycoproteins

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.
Humans ; Urinary Bladder Neoplasms/diagnosis* ; Carcinoma, Transitional Cell/pathology* ; Reproducibility of Results ; DNA Copy Number Variations ; Kidney Neoplasms ; Ureteral Neoplasms ; Sensitivity and Specificity

OBJECTIVE: To investigate and summarize the clinicopathological features, immunophenotype, differential diagnosis and prognosis analysis of mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: The data of thirteen cases of MTSCC were retrospectively analyzed, the clinical and pathological characteristics and immunohistochemical expression were summarized, and fluorescence in situ hybridization was detected. RESULTS: Among the thirteen patients, four were males and nine females, with a male-to-female ratio of 1 ∶2.25. The average age was 57.1 years, ranging from 39 to 78 years. The maximum diameter of the tumor was 2-12 cm. All cases had no symptoms, and were accidentally discovered, 3 cases underwent partial renal resection, 10 cases underwent radical renal resection, 9 cases were located in the left kidney, and 4 cases were located in the right kidney. Most of the cases showed the classical morphological changes, with 11 cases of nuclear grading [World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system] being G2 and 2 cases being G3. There were 6 cases of stage PT1a, 3 cases of PT1b, 2 cases of PT2a, and 1 case of PT2b and 1 case of PT3a. The positive rates of immunohistochemical staining were: vimentin, AE1/AE3, α-methylacyl-CoA racemase (αMACR) and cytokeratin (CK) 8/18, 100% (13/13); CK7, 92.3% (12/13); epithelial membrane antigen (EMA), 92.3% (12/13); CK20, 46.2% (6/13); CD10, 30.8% (4/13); synaptophysin (Syn), 7.7% (1/13); chromogranin A (CgA), CD57, WT1 and Ki-67, 0 (0/13), and fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and 17 were observed in any of the cases. The follow-up period was 6 months to 7 years and 6 months, 2 cases died after lung metastasis (one with ISUP/WHO grade G3, one with necrosis), and the remaining 11 cases had no recurrence and metastasis. CONCLUSION MTSCC is a unique type of low-grade malignancy kidney tumor, occurs predominantly in females, widely distributed in age, the current treatment method is surgical resection, and cases with necrosis and high-grade morphology are prone to recurrence and metastasis, although most cases have a good prognosis, but they still need close follow-up after surgery.
Humans ; Male ; Female ; Middle Aged ; Kidney Neoplasms/surgery* ; Carcinoma, Renal Cell/diagnosis* ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Adenocarcinoma, Mucinous/pathology* ; Kidney/pathology* ; Prognosis ; Necrosis

Objective: To investigate the clinicopathologic features,diagnosis and prognosis of pericytic tumor of the kidney. Methods: Three cases of pericytic tumor of the kidney (two cases were diagnosed as glomangiomyomas and one case as pericytic tumor,unclassified) were collected from the affiliated Hospital of Qingdao University between January 2014 to May 2021; the clinical and morphologic features, immunohistochemical and molecular characteristics were analyzed and the relevant literature was reviewed. Results: The three patients included one male and two females, with ages ranging from 21 to 70 years. In two patients the tumors were detected incidentally at physical examination and one patient presented with low back discomfort. Imaging showed a rounded nodular soft tissue density shadow in renal parenchyma, and enhancement scan showed uneven delayed enhancement. Grossly, two tumors were located in the renal hilum and one in the renal parenchyma; all were nodular. The tumors were measured in size from 1.6 cm to 5.1 cm (mean 4.1 cm) and showed gray or gray-red cut surface. Histologic examination showed the tumor cells were arranged in solid sheets or small nodules, closely related to vascular wall. Tumor cells were mostly epithelial-like with abundant cytoplasm, light eosinophilia, obscure boundary and round nuclei with visible nucleoli. Vague bundles and fascicular arrangements of smooth muscle component were noted in some areas, with transition of both components. There was no necrosis. By immunohistochemistry, the tumor cells strongly and diffusely expressed vimentin, SMA and collagen Ⅳ, two cases expressed CD34, all three cases expressed PDGFRB to varying extent, and the Ki-67 index was 2%-3%. PCR tests showed absent K-RAS, BRAF V600E gene mutation in all three cases. PDGFRB mutations in exons 3 and 18, respectively were found in two of the three cases by high-throughput sequencing, and no NOTCH 1/2/3 gene fusions were found in any of them. Follow-up information (range: 6-92 months) showed no evidence of local recurrence or distant metastasis in all three patients. Conclusions: Pericytic tumor of the kidney is a rare mesenchymal tumor originating in the kidney with differentiation to smooth muscle, most commonly glomus tumor. The mild pleomorphism, close relationship with vascular wall and spindled smooth muscle components suggest the diagnosis of the tumor. Expression of both epithelial and muscle-associated markers aids the diagnosis. PDGFRB gene mutations may have an important role in the development of this tumor. Most patients have a good prognosis, and a few cases have malignant biological behavior.
Adult ; Aged ; Biomarkers, Tumor/analysis* ; Collagen ; Diagnosis, Differential ; Female ; Glomus Tumor/pathology* ; Humans ; Ki-67 Antigen ; Kidney/pathology* ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Neoplasms, Connective and Soft Tissue ; Proto-Oncogene Proteins B-raf ; Receptor, Platelet-Derived Growth Factor beta ; Vimentin ; Young Adult

OBJECTIVE: To investigate the capabilities of classification models based on hierarchical fusion framework of multi-classifier using a random projection strategy for differentiation of renal cell carcinoma (RCC) from small renal angiomyolipoma (< 4 cm) without visible fat (AMLwvf). METHODS: We retrospectively collected the clinical data from 163 patients with pathologically proven small renal mass, including 118 with RCC and 45 with AMLwvf.Target region of interest (ROI) delineation was performed on an unenhanced phase (UP) CT image slice displaying the largest lesion area.The radiomics features were used to establish a hierarchical fusion method.On the projection-based level, the homogeneous classifiers were fused, and the fusion results were further fused at the classifier-based level to construct a multi-classifier fusion system based on random projection for differentiation of AMLwvf and RCC.The discriminative capability of this model was quantitatively evaluated using 5-fold cross validation and 4 evaluation indexes[specificity, sensitivity, accuracy and area under ROC curve (AUC)].We quantitatively compared this multi-classifier fusion framework against different classification models using a single classifier and several multi-classifier ensemble models. RESULTS: When the projection number was set at 10, the proposed hierarchical fusion differentiation framework achieved the best results on all the evaluation measurements.At the optimal projection number of 10, the specificity, sensitivity, average accuracy and AUC of the multi-classifier ensemble classification system for differentiation between AMLwvf and RCC were 0.853, 0.693, 0.809 and 0.870, respectively. CONCLUSION The proposed model constructed based on a multi-classifier fusion system using random projection shows better performance to differentiate RCC from AMLwvf than the AMLwvf and RCC discrimination models based on a single classification algorithm and the currently available benchmark ensemble methods.
Angiomyolipoma/pathology* ; Carcinoma, Renal Cell ; Diagnosis, Differential ; Humans ; Kidney Neoplasms/pathology* ; Retrospective Studies ; Tomography, X-Ray Computed/methods*

Renal angiomyolipoma (AML) is a common benign tumor in the urinary system, mainly composed of adipose tissue, blood vessels and muscle tissue. Renal AML is sporadic in most of patients, while a few are associated with tuberous sclerosis. Classical renal AML occurs predominantly in middle-aged females. Most cases are found incidentally during imaging examinations. The fat content makes AML have unique imaging characteristics and is easy to be identified with other renal tumors. However, the amount of fat varies in each tumor. AML that contains only microscopically detectable fat and whose amount of intratumoral fat may be too small to be identified on unenhanced computed tomography (CT) images is termed minimal fat or fat-poor renal AML, which appears as a high density shadow in the renal parenchyma on unenhanced CT images. Thus, it can be difficult to distinguish it from renal cell carcinoma (RCC) on imaging. Since the imaging findings are atypical, the diagnosis depends on pathological results. In addition, a few of AML can mimic malignant neoplasms. Recent studies suggested that AML might involve to peri-renal or renal sinus fat, regional lymphatics and other visceral organs, as well as inferior vena cava, which further makes the diagnosis more difficult. However, there is currently no reports about involvement of regional limphatics in minimal fat renal AML. In this article, we report a 27-year-old female patient without family history of tuberous sclerosis, who came to visit the hematologist because a high density shadow near the left kidney was found during CT scan which was accompanied by neck, armpits, groin, abdominal cavity and retroperitoneal lymph nodes enlargement. She was suspected of lymphoma in the beginning and transferred to Department of Urology to perform laparoscopic left renal mass and retroperitoneal lymph node excision and pathological examination for a definitive diagnosis. Finally, pathologic results revealed AML. Postoperative continuous lymphatic fistula developed and the retroperitoneal drainage of chylous fluid was 100-200 mL per day, lasting for 12 weeks. The fistula was successfully closed after conservative treatment including fasting and rehydration. This article summaries and discusses the diagnosis and treatment of renal AML with lymph nodes enlargement and the management of postoperative refractory lymphatic fistula by reviewing the related cases and literature.
Adult ; Angiomyolipoma/pathology* ; Carcinoma, Renal Cell/diagnosis* ; Female ; Fistula ; Humans ; Kidney Neoplasms/pathology* ; Lymph Nodes/pathology* ; Middle Aged

Store-operated calcium (Ca2+) entry (SOCE) is the principal Ca2+ entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.
Adolescent ; Adult ; Aged ; Blotting, Western ; Carcinoma, Renal Cell/*diagnosis/metabolism/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kidney Neoplasms/metabolism/*pathology ; Male ; Middle Aged ; Neoplasm Proteins/genetics/metabolism ; ORAI1 Protein/genetics/*metabolism ; Prognosis ; Retrospective Studies ; Stromal Interaction Molecule 1/genetics/metabolism ; Young Adult

Humans ; Kidney Neoplasms ; diagnosis ; pathology ; Lymphoma ; diagnosis ; pathology ; Nephrotic Syndrome ; diagnosis ; pathology

Xanthogranulomatous inflammation (XGI) is characterized histologically by the deposition of foamy macrophages and infiltration of inflammatory cells. While XGI is extremely rare, it has been reported in the gallbladder, kidney, stomach, and lymph nodes. A 61-year-old woman presented with epigastric pain for 2 weeks. Abdominal computed tomography and magnetic resonance imaging showed a pancreatic head mass with distal common bile duct wall thickening. Endoscopic ultrasonography followed by fine needle aspiration was performed, and subsequent pathology report revealed a benign disease. Because uncontrolled abdominal pain persisted and possibility of malignancy could not be excluded, Whipple's operation was eventually performed, and pathology report showed xanthogranulomatous pancreatitis (XGP). Herein, we report a case of symptomatic XGP mimicking of pancreas cancer. Although XGP is extremely rare, it should be considered as a differential diagnosis of neoplastic lesions of the pancreas.
Abdominal Pain ; Biopsy, Fine-Needle ; Common Bile Duct ; Diagnosis, Differential ; Endosonography ; Female ; Gallbladder ; Head ; Humans ; Inflammation ; Kidney ; Lymph Nodes ; Macrophages ; Magnetic Resonance Imaging ; Middle Aged ; Pancreas ; Pancreatic Neoplasms* ; Pancreatitis* ; Pathology ; Stomach

Malignant kidney neoplasms are the most frequently encountered solid kidney masses. Although renal cell carcinoma is the major renal malignancy, other solid malignant renal masses should be considered in the differential diagnosis of solid renal masses that do not contain a macroscopic fatty component. In this pictorial essay, we present the imaging findings of a primitive neuroectodermal tumor, primary liposarcoma of the kidney, primary neuroendocrine tumor, leiomyosarcoma, synovial sarcoma, malignant fibrous histiocytoma, sclerosing fibrosarcoma and renal metastasis of osteosarcoma.
Bone Neoplasms/secondary ; Carcinoma, Renal Cell/pathology/radiography ; Diagnosis, Differential ; Fibrosarcoma/radiography ; Histiocytoma/radiography ; Humans ; Kidney Neoplasms/*pathology/radiography ; Leiomyosarcoma/pathology/radiography ; Magnetic Resonance Imaging ; Middle Aged ; Neuroectodermal Tumors, Primitive/pathology/radiography ; Osteosarcoma/pathology ; Sarcoma ; Sarcoma, Synovial/radiography ; Tomography, X-Ray Computed