Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of low grade oncocytic tumors (LOT) of the kidney with CK7+/CD117- staining pattern for enhancing the understanding of renal LOT. Methods: The clinical data, histological morphology and immunophenotypes of seven renal LOT cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine from January 2017 to April 2021 were analyzed. The patients were followed up. Among the seven patients, five underwent high-throughput DNA targeted sequencing, and their molecular characteristics were analyzed. Results: The patients' age ranged 59-82 years, with an average of 70 years. There were 2 males and 5 females. The boundary of the tumor was clear. The tumor cells had homogeneous eosinophilic cytoplasm and round or oval nuclei, with a perinuclear halo. Small basophilic nucleoli were conspicuous (WHO/International Society of Urological Pathology grade 2). In the hypercellular areas, the tumor cells were mainly arranged in dense solid or nest. In the stroma, there were dilated veins, thick-walled arterioles and thick collagen fiber bundles that divided the cells into pseudonodules. In the sparsely cellular area, the tumor cells were arranged in the so-called "tissue culture" fashion. In addition, the stroma contained fresh hemorrhagic foci and lymphoid aggregates. High-throughput sequencing of 5 cases revealed that one case harbored mTOR gene missense mutation and another case harbored TSC1 frameshift mutation. Conclusions: LOT of the kidney is an indolent tumor with an overall good prognosis. Pathologists should not misdiagnose it as renal oncocytoma and chromophobe renal cell carcinoma.
Adenoma, Oxyphilic/pathology* ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/pathology* ; Collagen ; Female ; Humans ; Immunohistochemistry ; Kidney/pathology* ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Proto-Oncogene Proteins c-kit/metabolism* ; TOR Serine-Threonine Kinases

OBJECTIVE: To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors. METHODS: DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation. RESULTS: Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors. CONCLUSION The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.
Adenoma, Oxyphilic/genetics* ; Biomarkers, Tumor/metabolism* ; Cell Adhesion Molecules/metabolism* ; DNA Methylation ; GPI-Linked Proteins/metabolism* ; Humans ; Hyaluronoglucosaminidase/metabolism* ; Immunohistochemistry ; Middle Aged ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

Objective: To explore clinicopathological features of low-grade oncocytic tumor (LOT) of the kidney and to analyze its relationship to hybrid oncocytic/chromophobe tumor (HOCT) of the kidney, renal oncocytoma (RO), and chromophobe renal cell carcinoma (chRCC). Methods: Seven LOTs were identified from the pathologic archives of two hospitals, including Xiangya Hospital (5 cases) and the Second Xiangya Hospital (2 cases) of Central South University between 2012 and 2019. Clinical data of the LOTs were collected. The tumor morphology was analyzed and immunohistochemistry was performed. Results: All LOTs occurred in adults, aged from 49 to 72 years (median 56.0 years, mean 60.7 years). The tumor size ranged from 2.5 to 6.0 cm (median 4.3 cm, mean 4.3 cm). There were three male and four female patients. Three cases occurred in the left kidney and four in the right. All the tumors were solitary lesions without the clinicopathologic background of Birt-Hogg-Dubé (BHD) syndrome or oncocytosis. Five patients had available follow-up data (follow-up period 23-95 months, median 69.0 months, mean 64.6 months) and all were alive without disease. Microscopically, all LOTs were well-circumscribed (7/7). Three LOTs were partly encapsulated. The tumors demonstrated a predominant growth pattern comprising prominently compact small nests surrounded by delicately branching thin-walled blood vessels, imparting an organoid architecture (7/7), but variable numbers of glandular or gland-like structures were often seen among the small nests (7/7). There were frequently areas with loose, edematous stroma, and the tumor cells exhibited reticular, trabecular, or single cell arrangements (6/7). Focal hemorrhage was also commonly present in both compact and loose areas (5/7). In addition, focally cystic formation and ossification occurred in the compact area of one case and in the loose area of another case. The tumor cells in LOT showed intermediate cytologic characteristics between RO and chRCC, including abundantly eosinophilic granular cytoplasm, ovoid to round nuclei with mostly smooth contours, discernable small nucleoli (RO features), frequently delicate perinuclear halos, and occasional binucleation (chRCC features). The tumors were typically CK7-positive and CD117-negative (7/7), and variable staining for PAX8 (5/7), P504s (2/7), and vimentin (1/7). They were negative for CK20, CD10 and FOXI1. All tumors retained SDHB immunostaining. Conclusions: LOT is a rare and indolent oncocytic renal tumor with homogeneously intermediate cytologic features between RO and chRCC. There are some clinicopathologic overlaps between LOT and sporadic HOCT. The distinctive morphology and immunophenotype of LOT suggest that it is potentially a distinct tumor entity.
Adenoma, Oxyphilic/pathology* ; Adult ; Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/pathology* ; Female ; Forkhead Transcription Factors ; Humans ; Keratin-7 ; Kidney/pathology* ; Kidney Neoplasms/pathology* ; Male

Adenoma, Oxyphilic/surgery* ; Adrenal Cortex Neoplasms/surgery* ; Adrenocortical Adenoma/surgery* ; Humans

OBJECTIVE: To summarize and analyze the clinical data and prognosis of the patients with Hürthle cell tumor (HCT) in order to raise the clinicians' awareness of the disease. METHODS: The clinical data on patients with histopathologically proven HCT, without other thyroid carcinomas, were collected retrospectively in Peking University First Hospital from January 2001 to February 2017. All the patients underwent surgery due to thyroid nodules. The follow-up information was also collected. RESULTS: A total of 100 patients were enrolled in the current study. All of them were diagnosed with Hürthle cell adenoma (HCA). There were 77 females and 23 males, with the male-to-female ratio of 1 : 3.3. The average age of these patients was (52±14) years at the time of operation. Fifty-one patients were found their thyroid nodules accidentally by ultrasonography during their health check-ups. 69.4% of the 49 symptomatic patients presented with painless cervical nodules. 83.0% HCA patients were combined with multinodular goiters (MNGs). 88.4% (76/86) patients were euthyroid and 53.8% (21/39) had increasing thyroglobulin levels. The mean longest diameter of HCAs was (3.2±1.5) cm (range: 0.9-7.3 cm) on ultrasonography. There were a series of sonographic features of HCA, such as larger, solidity, hypoecho, a smooth outline, intranodular vascularization, perinodular vascularization, absence of calcification in nodules and absence of enlarged cervical lymph nodes. Compared with the histological diagnosis, the diagnostic accuracy by frozen section (FS) during operation was 97.4%. Twenty-nine patients were followed up with an average period of (49.2±22.1) months and none of them had local recurrence or cervical lymph node metastasis. Six patients accepted thyroid hormone replacement treatment and one had thyrotoxicosis due to over-dose. CONCLUSION HCA is more common in women. It is often found accidentally by ultrasonography during their health check-ups or presented with painless cervical nodules. It is combined with MNG frequently. HCA exhibits numerous sonographic features but not unique. FS during operation is a reliable method to identify HCA with high diagnostic accuracy. Patients with thyroid hormone administration should be monitored for thyroid function after thyroid surgery.
Adenoma, Oxyphilic/surgery* ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology* ; Oxyphil Cells ; Retrospective Studies ; Thyroid Neoplasms/surgery*

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterized by the formation of hair follicle tumors, kidney tumors, and pulmonary cysts with recurrent spontaneous pneumothorax. A 44-year-old woman visited Wonkwang University Hospital with mild dyspnea. A chest X-ray on admission revealed pneumothorax in both lung fields. Chest computed tomography (CT) revealed both pneumothorax and multiple, irregularly shaped, variable-sized cysts in both lung fields. Upon physical examination, white dome-shaped papules were observed on the face. Histological examination of the skin lesion confirmed fibrofolliculoma, and genetic studies revealed a folliculin gene mutation. Abdominal CT revealed a 1-cm small solid renal mass at the lower pole of the right kidney. We surgically removed the renal tumor, and a histological diagnosis of oncocytoma was made. Here, we report a case of BHD that demonstrated all three clinical manifestations; this is the first case report of its kind in Korea.
Adenoma, Oxyphilic ; Adult ; Birt-Hogg-Dube Syndrome ; Diagnosis ; Dyspnea ; Estrone ; Female ; Hair Follicle ; Humans ; Kidney ; Kidney Neoplasms ; Korea ; Lung ; Physical Examination ; Pneumothorax ; Skin ; Thorax ; Tomography, X-Ray Computed

A renal oncocytoma was diagnosed in an 8-year-old female Maltese dog with a history of renal cysts. Tumor cells were not detected until six months after observation of renal cysts. Nephrectomy was performed to treat the neoplasia. Tumor-like masses with numerous nodules were observed in the inner surface of cysts present in the caudal part of the left kidney. Histologically, the tumor consisted of cells with abundant eosinophilic cytoplasm. The diagnosis was based on histological features, periodic acid-Schiff reaction, and immunohistochemical cytokeratin staining. Based on a literature review, this is the first canine renal oncocytoma case reported in Korea.
Adenoma, Oxyphilic ; Animals ; Child ; Cytoplasm ; Diagnosis ; Dogs ; Eosinophils ; Female ; Humans ; Keratins ; Kidney ; Korea ; Nephrectomy ; Periodic Acid-Schiff Reaction

OBJECTIVE: To summarize the experience of diagnosis and surgical treatment of renal oncocytoma, and to evaluate the surgical results based on follow-up results, in order to find the best strategy. METHODS: In the study, 21 cases with renal oncocytoma from December 2003 to April 2016 in Peking University Third Hospital were retrospectively analyzed, including 4 males, and 17 females, with 10 cases on the right side and 11 cases on the left side. Their age was between 15 to 80 years (average: 58 years). Ultrasound or CT examination after admission was conducted. Ultrasound examination showed solid nodules. CT manifestations were solid masses with enhancement, and the tumor size was between 1.5 cm to 6.5 cm (average: 3.3 cm). Of the 21 cases, 9 were located in the middle of kidney, 7 were located in the upper pole, and 5 were located in the lower pole. After preoperative examination, according to the size and location of the tumor, laparoscopic partial nephrectomy or laparoscopic nephrectomy was performed, respectively. RESULTS: All the operations were successful, in which 17 cases underwent laparoscopic partial nephrectomy (including 3 cases which were converted to open surgery), and 4 cases underwent laparoscopic radical nephrectomy. The operation time ranged from 75 to 274 min (mean: 144 min), and the blood loss ranged from 10 to 1 000 mL (mean: 115 mL). The postoperative hospital stay time ranged from 6 to 13 d (average: 8.2 d). The pathological results were all renal oncocytoma. In the study, 17 cases were followed up while 4 cases were lost to follow-up. The follow-up time ranged from 12 to 175 months (mean: 44 months). One case died in 20 months after operation with unknown reason, and there were no recurrence or metastasis in the other 16 cases. CONCLUSION Renal oncocytoma is a benign tumor with good prognosis. Enhanced CT is an effective diagnostic method in assistant examination, but it is difficult to differentiate clear cell carcinoma only from the naked eye. It is worthwhile to measure CT value at different stages of the tumor by picture archiving and communication systems (PACS), and to compare with CT value of adjacent kidney tissue may improve the diagnostic efficiency of CT. Laparoscopic surgery is an effective treatment for renal oncocytoma. We recommend laparoscopic partial nephrectomy for the patients with renal oncocytoma as the best choice if conditions permit.
Adenoma, Oxyphilic/therapy* ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; Female ; Humans ; Kidney Neoplasms/therapy* ; Laparoscopy ; Male ; Middle Aged ; Nephrectomy ; Retrospective Studies ; Young Adult

BACKGROUNDThe difference between renal oncocytomas (RO) and renal clear cell carcinomas (RCCs) presents the greatest diagnostic challenge. The aim of this study was to retrospectively determine if RO and RCCs could be differentiated on computed tomography (CT) images on the basis of their enhancement patterns with a new enhancement correcting method.

METHODSForty-six patients with a solitary renal mass who underwent total or partial nephrectomy were included in this study. Fourteen of those were RO and 32 were RCCs. All patients were examined with contrast-enhanced CT. The pattern and degree of enhancement were evaluated. We selected the area that demonstrated the greatest degree of enhancement of the renal lesion in the corticomedullary nephrographic and excretory phase images. Regions of interest (ROI) were also placed in adjacent normal renal cortex for normalization. We used the values of the normal renal cortex that were measured at the same time as divisors. The ratios of lesion-to-renal cortex enhancement were calculated for all three phases. The Student's t-test and Pearson's Chi-square test were used for statistical analyses.

RESULTSAll RCCs masses showed contrast that appeared to be better enhanced than RO on all contrast-enhanced phases of CT imaging, but there was no significant difference in absolute attenuation values between these two diseases (P > 0.05). The ratio of lesion-to-cortex attenuation in the corticomedullary phase showed significantly different values between RO and RCCs. The degree of contrast enhancement in RCCs was equal to or greater than that of the normal renal cortex, but it was less than that of the normal cortex in RO in the corticomedullary phase. The ratio of lesion-to-cortex attenuation in the corticomedullary phase was higher than the cut off value of 1.0 in most RCCs (84%, 27/32) and lower than 1.0 in most RO (93%, 13/14) (P < 0.05). In the nephrographic phase, the ratio of lesion-to-cortex attenuation was higher than that in the corticomedullary phase in most RO (71%, 10/14), showing a prolonged enhancement pattern; and was lower than that in most RCCs (97%, 31/32), showing an early washout pattern (P < 0.05). In the differentiation of RO from RCCs, the sensitivity was 93%, specificity 84%, positive predictive value 72%, negative predictive value 84%, and accuracy for RO was 87, if the ratio of lesion-to-cortex attenuation in a cortex phase was lower than the cutoff value of 1.0. The sensitivity was 71%, specificity was 97%, positive predictive value was 91%, negative predictive value was 91%, and accuracy for RO was 89%, if the ratio of lesion-to-cortex attenuation in nephrographic phase was higher than that in the corticomedullary phase.

CONCLUSIONSThe ratios of renal lesion-to-cortex attenuation ratios may be helpful in differentiating RO from RCCs.

Adenoma, Oxyphilic ; diagnosis ; diagnostic imaging ; Adult ; Aged ; Carcinoma, Renal Cell ; diagnosis ; diagnostic imaging ; Female ; Humans ; Kidney Neoplasms ; diagnosis ; diagnostic imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo study the immunohistochemical expression of S100A1, GLUT-1 and Cavolin-1 and its diagnostic significance in renal tumors with oncocytic features.

METHODSTissue microarray and immunohistochemical staining for S100A1, GLUT-1 and Cavolin-1 were carried out in 59 cases of renal tumors with oncocytic features, including 19 cases of renal oncocytoma, 15 cases of clear cell renal cell carcinoma (CCRCC) with eosinophilic cells, 11 cases of eosinophilic variant of chromophobe renal cell carcinoma, 7 cases of oncocytic papillary renal cell carcinoma and 7 cases of epithelioid angiomyolipoma.

RESULTSS100A1 was expressed in renal oncocytoma, with a positive propotion of 16/19 (including 14 cases showing widespread and strong positivity). On the other hand, the rate of expression of S100A1 was 2/11 in eosinophilic variant of chromophobe renal cell carcinoma, 10/15 in CCRCC with eosinophilic cells, 3/7 in oncocytic papillary renal cell carcinoma and 6/7 in epithelioid angiomyolipoma (P>0.05). The difference of S100A1 expression between renal oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma was statistically significant. GLUT-1 was located in cell membrane, with a positive rate of 13/15 in CCRCC with eosinophilic cells, 7/19 in renal oncocytoma, 4/7 (weak) in oncocytic papillary renal cell carcinoma, 1/11 in eosinophilic variant of chromophobe renal cell carcinoma and 0/7 in epithelioid angiomyolipoma. The rate of expression of Cav-1 was 6/15 in CCRCC with eosinophilic cells, 2/7 in oncocytic papillary renal cell carcinoma, 5/7 in epithelioid angiomyolipoma, 2/11 (weak) in eosinophilic variant of chromophobe renal cell carcinoma and 0/19 in renal oncocytoma. S100A1 showed high sensitivity and 50% specificity in the diagnosis of renal oncocytoma. GLUT-1 and Cav-1 showed high specificity and sensitivity in the diagnosis of CCRCC and epithelioid angiomyolipoma.

CONCLUSIONSS100A1 is widely expressed in various oncocytic renal neoplasms and helpful in differential diagnosis of renal oncocytoma from eosinophilic variant of chromophobe renal cell carcinoma, but not from other 3 oncocytic renal tumors. Overexpression of GLUT-1 can be used in distinction between CCRCC and renal oncocytoma. Cav-1 is widely expressed in CCRCC and epithelioid angiomyolipoma but not in renal oncocytoma. Cav-1 expression thus rules out renal oncocytoma.

Adenoma, Oxyphilic ; diagnosis ; metabolism ; Angiomyolipoma ; diagnosis ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; diagnosis ; metabolism ; Caveolin 1 ; metabolism ; Diagnosis, Differential ; Glucose Transporter Type 1 ; metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; diagnosis ; metabolism ; S100 Proteins ; metabolism ; Sensitivity and Specificity