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 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 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*

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

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

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

The prevalence of small renal masses (SRM) has risen, paralleling the increased usage of cross-sectional imaging. A large proportion of these SRMs are not malignant, and do not require invasive treatment such as nephrectomy. Therefore, differentation between early renal cell carcinoma (RCC) and benign SRM is critical to achieve proper management. This article reviews the radiological features of benign SRMs, with focus on two of the most common benign entities, angiomyolipoma and oncocytoma, in terms of their common imaging findings and differential features from RCC. Furthermore, the role of percutaneous biopsy is discussed as imaging is yet imperfect, therefore necessitating biopsy in certain circumstances to confirm the benignity of SRMs.
Abdominal Fat/pathology ; Adenoma, Oxyphilic/diagnosis/radiography/ultrasonography ; Angiomyolipoma/diagnosis/radiography/ultrasonography ; Carcinoma, Renal Cell/*diagnosis/radiography/ultrasonography ; Diagnosis, Differential ; Humans ; Kidney Neoplasms/*diagnosis/*radiography/ultrasonography ; Leiomyoma/diagnosis/radiography/ultrasonography

PURPOSE: To investigate and distinguish the computed tomography (CT) characteristics of chromophobe renal cell carcinoma (chRCC) and renal oncocytoma. MATERIALS AND METHODS: Fifty-one patients with renal oncocytoma and 120 patients with chRCC, diagnosed by surgery between November 2005 and June 2015, were studied retrospectively. Two observers, who were urologists and unaware of the pathological results, reviewed the preoperative CT images. The tumors were evaluated for size, laterality, tumor type (ball or bean pattern), central stellate scar, segmental enhancement inversion, and angular interface pattern and tumor complexity. To accurately analyze the mass-enhancing pattern of renal mass, we measured Hounsfield units (HUs) in each phase and analyzed the mean, maximum, and minimum HU values and standard deviations. RESULTS: There were 51 renal oncocytomas and 120 chRCCs in the study cohort. No differences in clinical and demographic characteristics were observed between the two groups. A central stellate scar and segmental enhancement inversion were more likely in oncocytomas. However, there were no differences in ball-/bean-type categorization, enhancement pattern, and the shape of the interface between the groups. Higher HU values tended to be present in the corticomedullary and nephrogenic phases in oncocytomas than in chRCC. Receiver-operating characteristic curve analysis showed that the presence of a central stellate scar and higher mean HU values in the nephrogenic phase were highly predictive of renal oncocytoma (area under the curve=0.817, p<0.001). CONCLUSIONS: The appearance of a central stellate scar and higher mean HU values in the nephrogenic phase could be useful to distinguish renal oncocytomas from chRCCs.
Adenoma, Oxyphilic/pathology/*radiography ; Carcinoma, Renal Cell/pathology/*radiography ; Diagnosis, Differential ; Female ; Humans ; Kidney Neoplasms/pathology/*radiography ; Male ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed